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1.
Front Immunol ; 12: 688802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177943

RESUMO

Palearctic vipers are medically significant snakes in the genera Daboia, Macrovipera, Montivipera, and Vipera which occur throughout Europe, Central Asia, Near and Middle East. While the ancestral condition is that of a small-bodied, lowland species, extensive diversification has occurred in body size, and niche specialization. Using 27 venom samples and a panel of in vitro coagulation assays, we evaluated the relative coagulotoxic potency of Palearctic viper venoms and compared their neutralization by three antivenoms (Insoserp Europe, VIPERFAV and ViperaTAb) and two metalloprotease inhibitors (prinomastat and DMPS). We show that variation in morphology parallels variation in the Factor X activating procoagulant toxicity, with the three convergent evolutions of larger body sizes (Daboia genus, Macrovipera genus, and Vipera ammodytes uniquely within the Vipera genus) were each accompanied by a significant increase in procoagulant potency. In contrast, the two convergent evolutions of high altitude specialization (the Montivipera genus and Vipera latastei uniquely within the Vipera genus) were each accompanied by a shift away from procoagulant action, with the Montivipera species being particularly potently anticoagulant. Inoserp Europe and VIPERFAV antivenoms were both effective against a broad range of Vipera species, with Inoserp able to neutralize additional species relative to VIPERFAV, reflective of its more complex antivenom immunization mixture. In contrast, ViperaTAb was extremely potent in neutralizing V. berus but, reflective of this being a monovalent antivenom, it was not effective against other Vipera species. The enzyme inhibitor prinomastat efficiently neutralized the metalloprotease-driven Factor X activation of the procoagulant venoms. In contrast, DMPS (2,3-dimercapto-1-propanesulfonic acid), which as been suggested as another potential treatment option in the absence of antivenom, DMPS failed against all venoms tested. Overall, our results highlight the evolutionary variations within Palearctic vipers and help to inform clinical management of viper envenomation.


Assuntos
Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fragmentos Fab das Imunoglobulinas/farmacologia , Inibidores de Metaloproteinases de Matriz/farmacologia , Compostos Orgânicos/farmacologia , Mordeduras de Serpentes/tratamento farmacológico , Unitiol/farmacologia , Venenos de Víboras/antagonistas & inibidores , Viperidae , Animais , Testes de Coagulação Sanguínea , Evolução Molecular , Humanos , Mordeduras de Serpentes/sangue , Mordeduras de Serpentes/enzimologia , Especificidade da Espécie , Fatores de Tempo , Venenos de Víboras/enzimologia
2.
BMC Neurol ; 20(1): 255, 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32593295

RESUMO

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.


Assuntos
Quelantes/administração & dosagem , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/uso terapêutico , Unitiol/administração & dosagem , Zinco/administração & dosagem , Adulto , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
3.
J Neurol ; 267(6): 1643-1650, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32060651

RESUMO

OBJECTIVE: A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done. METHODS: 100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination. RESULTS: At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls. CONCLUSIONS: Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.


Assuntos
Quelantes/farmacologia , Globo Pálido/diagnóstico por imagem , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/farmacologia , Substância Negra/diagnóstico por imagem , Unitiol/farmacologia , Adolescente , Adulto , Cobre/sangue , Cobre/urina , Feminino , Degeneração Hepatolenticular/sangue , Degeneração Hepatolenticular/urina , Humanos , Imageamento por Ressonância Magnética , Masculino , Avaliação de Resultados em Cuidados de Saúde , Adulto Jovem
4.
Biomolecules ; 10(2)2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033229

RESUMO

: High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.


Assuntos
Antídotos/uso terapêutico , Intoxicação por Arsênico/tratamento farmacológico , Arsênio/toxicidade , Quelantes/uso terapêutico , Animais , Antídotos/química , Antídotos/farmacologia , Arsênio/efeitos adversos , Intoxicação por Arsênico/etiologia , Intoxicação por Arsênico/metabolismo , Arsenicais/efeitos adversos , Quelantes/química , Quelantes/farmacologia , Dimercaprol/análogos & derivados , Dimercaprol/farmacologia , Dimercaprol/uso terapêutico , Água Potável/efeitos adversos , Humanos , Modelos Moleculares , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Succímero/química , Succímero/farmacologia , Succímero/uso terapêutico , Unitiol/química , Unitiol/farmacologia , Unitiol/uso terapêutico , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/toxicidade
5.
Protein Pept Lett ; 27(8): 801-807, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32003653

RESUMO

BACKGROUND: Ionic complementary peptide EAK-16 has been studies for anticancer drug delivery application. This is a 16 residues, short sequence peptide has ability to trosnform into micro/nanoparticle via self-assembly. However, it is still not clear that how this can bind with cell membrane to induce membrane leakage or delivering their cargo inside cell membrane. OBJECTIVE: The main objective of this work was to understand behaviour of secondary structure conformation of peptide in solution and at lipid membrane interfaces and membrane permeability of synthetic ionic complementary peptide EAK-16. The corresponding secondary structure conformation was evaluated. METHODS: We performed biophysical investigation to probe the interaction of synthesised ionic complementary peptide (EAK-16) with dimyristoylphospholcholine (DMPC) and dimyristoylphosphoserine (DMPS) membrane interfaces. The folding behaviours of EAK-16 were studied with Circular Dichroism (CD) spectroscopy. Membrane leakage with peptide was confirmed with calcein leakage assay. RESULTS: Our finding of this study showed that in aqueous phase EAK-16 was predominantly folded into ß-sheets. The temperature could alter the ß-sheets. However, in DMPC and DMPS membrane interfaces, EAK-16 adopted helical conformation. EAK-16 has preference in perturbing anionic compared Zwitterionic lipid vesicles. This study proposed that hydrophobic grooves of EAK-16 might be a key in the association with lipid bilayers. Secondly, a charge distribution of ionic residues would also support the orientation at lipid bilayers. This peptide membrane association would facilitate the membrane destabilisation. CONCLUSION: This study demonstrated the supporting evidence that EAK-16 could interact with lipid membranes and conforming to helical structure, while the helical conformation induced the lipid membrane leakage. Overall, this study provides a physical rationale that ionic complementary peptide can be a useful tool for designing and development of novel antibiotics and anticancer agents along its previous drug delivery applications.


Assuntos
Dimiristoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Peptídeos/química , Unitiol/química , Conformação Proteica em Folha beta
6.
BMC Nephrol ; 20(1): 374, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623560

RESUMO

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.


Assuntos
Anuria/complicações , Intoxicação por Arsênico/terapia , Quelantes/uso terapêutico , Terapia de Substituição Renal Contínua , Falência Renal Crônica/complicações , Intoxicação por Chumbo/terapia , Adulto , Animais , Intoxicação por Arsênico/complicações , Dimercaprol/uso terapêutico , Ácido Edético/uso terapêutico , Humanos , Falência Renal Crônica/terapia , Intoxicação por Chumbo/complicações , Masculino , Diálise Renal , Succímero/uso terapêutico , Unitiol/uso terapêutico
7.
Pediatr Emerg Care ; 35(10): 696-699, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27977534

RESUMO

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.


Assuntos
Exposição Ambiental/efeitos adversos , Intoxicação por Mercúrio/diagnóstico , Mercúrio/sangue , Instituições Acadêmicas/estatística & dados numéricos , Doença Aguda , Adolescente , Quelantes/uso terapêutico , Criança , Feminino , Humanos , Masculino , Mercúrio/urina , Intoxicação por Mercúrio/tratamento farmacológico , Intoxicação por Mercúrio/patologia , Medicina de Emergência Pediátrica , Penicilamina/uso terapêutico , Turquia/epidemiologia , Unitiol/uso terapêutico
8.
Acta Clin Belg ; 74(3): 200-202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29912651

RESUMO

BACKGROUND: Fixed drug eruptions (FDE) are characterized by recurrent, usually solitary erythematous or dark red macular, plaque or bullous lesions, all at the same site. Among the first choices for antidotal treatment in mercury exposure, 2,3-dimercapto-1-propanesulfonic acid (DMPS) is generally a drug with a low incidence of side effects. FDE due to DMPS was not detected in our literature research and so we aimed to present this rare case. CASE REPORT: Forty-eight-year-old male patient, gunpowder and explosives factory worker, was admitted to our hospital because of mercury exposure and we started DMPS treatment. On the second day of chelation treatment, swelling and felting on lips and complaints of wound formation in genital areas started. Annular, purple color plaque on penis with no angioedema was observed. Case was regarded as FDE. Systemic and topical steroid therapy was started after termination of chelation therapy and lesions regressed with steroids. DISCUSSION: Drug eruptions are substantially common dermatological problems and can be seen in about 2.2% of inpatients. The most common unexpected effects of DMPS are allergic skin reactions. The clinical state regress rapidly after the cessation of chelation therapy.


Assuntos
Quelantes/efeitos adversos , Erupção por Droga/tratamento farmacológico , Intoxicação por Mercúrio/tratamento farmacológico , Unitiol/efeitos adversos , Quelantes/uso terapêutico , Erupção por Droga/etiologia , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Pênis/induzido quimicamente , Doenças do Pênis/tratamento farmacológico , Unitiol/uso terapêutico
9.
Medicine (Baltimore) ; 97(50): e13744, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558096

RESUMO

RATIONALE: Both Wilson disease (WD) and Oculocutaneous Albinism (OCA) are rare autosomal recessive disorders that are caused by mutations on chromosome 13 and chromosome 11, respectively. Here, we report on a patient with coexisting WD and OCA, initially presenting episodes of tremors. PATIENT CONCERNS: WD is a disorder of copper metabolism. The main sites of copper accumulation are the liver and the brain, resulting in hepatic symptoms. OCA is a disorder of melanin biosynthesis, characterized by a generalized reduction in pigmentation of the eyes (oculo-), skin (-cutaneous), and hair. DIAGNOSIS: The diagnosis of WD was confirmed by neurological symptoms, metabolism tests, and MRI scans. Interestingly, the patient also had very light skin color, blond hair and eyebrows, and dark brown eyelashes and irises. Because the association of dermatologic signs in WD has rarely been reported, OCA was highly suspected based on these clinical findings. Genetic analysis was subsequently conducted, and the results revealed the p. (Arg778Leu) mutation in 1 allele and the p. (Asn1270Ser) mutation in the other allele of the ATP7B gene, confirming the diagnosis of WD; the p. (D456fs) mutation in 1 allele and the p. (R299H) mutation in the other allele of the TYR gene, confirming the diagnosis of OCA. The family history was positive for WD with a 14-year-old younger brother also being diagnosed with it. Her parents are negative for OCA and WD. INTERVENTIONS: Sodium dimercaptopropanesulfonate (DMPS) was given during hospitalization. D-penicillamine and zinc sulfate treatment was initiated after discharge for long-term control. OUTCOMES: Postural and intention tremor disappeared, and other symptoms and signs markedly improved after treatment. LESSONS: In this study, we reported on the first case of a child who simultaneously presented WD and OCA, bringing up the possibility of a presumable link between these 2 rare diseases.


Assuntos
Albinismo Oculocutâneo/complicações , Albinismo Oculocutâneo/metabolismo , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/metabolismo , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/genética , Grupo com Ancestrais do Continente Asiático/genética , Adstringentes/uso terapêutico , Quelantes/uso terapêutico , Feminino , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética/métodos , Mutação , Penicilamina/administração & dosagem , Penicilamina/uso terapêutico , Resultado do Tratamento , Unitiol/administração & dosagem , Unitiol/uso terapêutico , Adulto Jovem , Sulfato de Zinco/administração & dosagem , Sulfato de Zinco/uso terapêutico
10.
Eur Biophys J ; 47(8): 939-950, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29971510

RESUMO

In this work, the effects of the anti-hypertensive drug amlodipine in native and PEGylated forms on the malfunctioning of negatively charged lipid bilayer cell membranes constructed from DMPS or DMPS + DMPC were studied by molecular dynamics simulation. The obtained results indicate that amlodipine alone aggregates and as a result its diffusion into the membrane is retarded. In addition, due to their large size aggregates of the drug can damage the cell, rupturing the cell membrane. It is shown that PEGylation of amlodipine prevents this aggregation and facilitates its diffusion into the lipid membrane. The interaction of the drug with negatively charged membranes in the presence of an aqueous solution of NaCl, as the medium, is investigated and its effects on the membrane are considered by evaluating the structural properties of the membrane such as area per lipid, thickness, lipid chain order and electrostatic potential difference between bulk solution and lipid bilayer surface. The effect of these parameters on the diffusion of the drug into the cell is critically examined and discussed.


Assuntos
Anlodipino/farmacologia , Membrana Celular/efeitos dos fármacos , Dimiristoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Simulação de Dinâmica Molecular , Unitiol/química , Membrana Celular/química , Membrana Celular/metabolismo , Relação Dose-Resposta a Droga , Conformação Molecular , Polietilenoglicóis/química , Cloreto de Sódio/farmacologia , Eletricidade Estática
11.
Retina ; 38(9): 1688-1698, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28723845

RESUMO

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.


Assuntos
Instituições de Assistência Ambulatorial/normas , Eficiência Organizacional , Oftalmopatias/terapia , Oftalmologia , Satisfação do Paciente , Gestão da Qualidade Total , Fluxo de Trabalho , Humanos , Unitiol
12.
J Tradit Chin Med ; 38(5): 781-786, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-32185997

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of gandouling plus sodium dimercaptosulphonate (DMPS) on neurological Wilson's disease (WD) in patients. METHODS: We retrospectively evaluated the clinical records of 125 WD patients with neurological syndromes who were treated with gandouling plus sodium DMPS or DMPS used alone. All patients had a history of neurological deterioration during their diseases courses. The clinical efficacies, adverse reactions, and results of the various hematological and biochemical investigations were recorded for statistical analysis. RESULTS: 92.30% (60 patients) of the WD patients treated with the combined therapy experienced an improved or stable neurological condition paralleled by a significantly improved GAS score. Meanwhile, the WBC and PLT counts stabilized, liver function and renal function were improved or remained stable. The combined therapy also obviously promoted the 24-h urinary copper excretion. In particular, only 30.76% of the WD patients experienced mild adverse reactions, including neurological deterioration in 5 patients (7.69%), hepatic worsening in 1 subject (1.89%), which was less frequently than those in the control group treated with DMPS only. CONCLUSION: Our findings indicate that the safety and efficacy of gandou-ling plus DMPS is superior to those of DMPS used alone in the WD patients with neurological symptoms.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Degeneração Hepatolenticular/tratamento farmacológico , Unitiol/administração & dosagem , Adolescente , Adulto , China , Quimioterapia Combinada/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Degeneração Hepatolenticular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Unitiol/efeitos adversos , Adulto Jovem
13.
Arch Toxicol ; 91(12): 3787-3797, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29063135

RESUMO

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.


Assuntos
Intoxicação por Arsênico/tratamento farmacológico , Quelantes/uso terapêutico , Intoxicação do Sistema Nervoso por Chumbo/tratamento farmacológico , Intoxicação do Sistema Nervoso por Mercúrio/tratamento farmacológico , Ácido Edético/uso terapêutico , Humanos , Monensin/uso terapêutico , Succímero/uso terapêutico , Unitiol/uso terapêutico
14.
Colloids Surf B Biointerfaces ; 160: 281-288, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28946063

RESUMO

GM1 has generally been considered as the major receptor that binds to cholera toxin subunit B (CTB) due to its low dissociation constant. However, using a unique nanocube sensor technology, we have shown that CTB can also bind to other glycolipid receptors, fucosyl-GM1 and GD1b. Additionally, we have demonstrated that GM2 can contribute to CTB binding if present in a glycolipid mixture with a strongly binding receptor (GM1/fucosyl-GM1/GD1b). This hetero-multivalent binding result was unintuitive because the interaction between CTB and pure GM2 is negligible. We hypothesized that the reduced dimensionality of CTB-GM2 binding events is a major cause of the observed CTB binding enhancement. Once CTB has attached to a strong receptor, subsequent binding events are confined to a 2D membrane surface. Therefore, even a weak GM2 receptor could now participate in second or higher binding events because its surface reaction rate can be up to 104 times higher than the bulk reaction rate. To test this hypothesis, we altered the surface reaction rate by modulating the fluidity and heterogeneity of the model membrane. Decreasing membrane fluidity reduced the binding cooperativity between GM2 and a strong receptor. Our findings indicated a new protein-receptor binding assay, that can mimic complex cell membrane environment more accurately, is required to explore the inherent hetero-multivalency of the cell membrane. We have thus developed a new membrane perturbation protocol to efficiently screen receptor candidates involved in hetero-multivalent protein binding.


Assuntos
Toxina da Cólera/química , Gangliosídeo G(M1)/química , Gangliosídeo G(M2)/química , Bicamadas Lipídicas/química , Sítios de Ligação , Sequência de Carboidratos , Membrana Celular/química , Toxina da Cólera/metabolismo , Dimiristoilfosfatidilcolina/química , Dimiristoilfosfatidilcolina/metabolismo , Gangliosídeo G(M1)/metabolismo , Gangliosídeo G(M2)/metabolismo , Cinética , Bicamadas Lipídicas/metabolismo , Nanopartículas Metálicas/química , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Ligação Proteica , Dióxido de Silício/química , Termodinâmica , Unitiol/química , Unitiol/metabolismo
15.
Free Radic Biol Med ; 112: 445-451, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28844937

RESUMO

In light of the recent lead contamination of the water in Flint, Michigan and its potential adverse outcomes, much research and media attention has turned towards the safety profile of commonly used chelators. Dimercapto-1-propanesulfonic acid (DMPS) typically used in the treatment of lead, mercury and arsenic poisoning also displays a high affinity towards transition metals such as zinc and copper, essential for biological functioning. It is given in series of dosages (0.2-0.4g/day) over a long period, and has the ability to enter cells. In this work, we investigated the mechanism through which increasing concentrations of DMPS alter oocyte quality as judged by changes in microtubule morphology (MT) and chromosomal alignment (CH) of metaphase II mice oocyte. The oocytes were directly exposed to increasing concentration of DMPS (10, 25, 50, 100 and 300µM) for four hours (time of peak plasma concentration after administration) and reactive oxygen species (mainly hydroxyl radical and superoxide) and zinc content were measured. This data showed DMPS plays an important role in deterioration of oocyte quality through a mechanism involving zinc deficiency and enhancement of reactive oxygen species a major contributor to oocyte damage. Our current work, for the first time, demonstrates the possibility of DMPS to negatively impact fertility. This finding can not only help in counseling reproductive age patients undergoing such treatment but also in the development of potential therapies to alleviate oxidative damage and preserve fertility in people receiving heavy metal chelators.


Assuntos
Quelantes/farmacologia , Radical Hidroxila/agonistas , Oócitos/efeitos dos fármacos , Superóxidos/agonistas , Unitiol/farmacologia , Zinco/metabolismo , Animais , Cátions Bivalentes , Células Cultivadas , Quelantes/metabolismo , Criopreservação , Relação Dose-Resposta a Droga , Feminino , Radical Hidroxila/metabolismo , Metáfase/efeitos dos fármacos , Camundongos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Oócitos/citologia , Oócitos/metabolismo , Superóxidos/metabolismo , Unitiol/metabolismo
16.
Pediatrics ; 140(2)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28701428

RESUMO

Mercury (Hg) poisoning is considered a rare disease by the National Institutes of Health and the diagnosis can present great challenges to clinicians. Children who are exposed to Hg can present with a wide variety of symptoms, including acrodynia, tremor, excessive salivation, and psychiatric symptoms, including insomnia. However, endocrinologic manifestations from Hg exposure are less well known. This is a case report of a 12-year-old boy who presented with body rash, irritability, insomnia, and profuse sweating after returning from a summer camp. The child was initially managed in the outpatient setting, and the investigation was mainly targeted toward infectious etiology, including Rocky Mountain spotted fever and Lyme disease. He was eventually admitted to the hospital with altered mental status and was noted to have hyponatremia with serum sodium of 121 mEq/L. Thyroid studies also revealed elevated free thyroxine levels in the presence of normal triiodothyronine and thyrotropin. The patient developed hypertension and tachycardia, and was found to have elevated 24-hour vanillylmandelic acid and metanephrines. Finally, heavy metal measurements revealed a blood Hg level that was greater than the reference values of 0 to 9 ng/mL. Chelation treatment with 2,3-dimercaptopropane-1-sulfonate was subsequently initiated and over a period of 8 months his symptoms resolved and his thyroid function test returned to normal. This case highlights some of the challenges commonly encountered in identifying Hg exposure. More importantly, it illustrates that exposure to Hg should be considered in children who present with the symptoms and abnormal endocrinologic test results described in this report.


Assuntos
Hipertireoxinemia/diagnóstico , Hiponatremia/diagnóstico , Intoxicação por Mercúrio/diagnóstico , Metanefrina/sangue , Doenças Raras , Ácido Vanilmandélico/sangue , Terapia por Quelação , Criança , Diagnóstico Diferencial , Humanos , Hipertireoxinemia/etiologia , Hiponatremia/etiologia , Masculino , Intoxicação por Mercúrio/tratamento farmacológico , Admissão do Paciente , Unitiol/uso terapêutico
17.
J Pharmacol Sci ; 134(2): 108-115, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28648300

RESUMO

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.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Nefropatias/tratamento farmacológico , Succímero/uso terapêutico , Unitiol/uso terapêutico , Animais , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Camundongos , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/genética , Transportador 2 de Cátion Orgânico/metabolismo , RNA Mensageiro/metabolismo , Succímero/farmacologia , Unitiol/farmacologia
18.
Complement Med Res ; 24(3): 175-181, 2017.
Artigo em Alemão | MEDLINE | ID: mdl-28641283

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3-5 years in most cases. New approaches to treating this disease are needed. Here, we report a successful therapy. CASE REPORT: In a 49-year-old male patient suffering from muscle weakness and fasciculations, progressive muscular atrophy, a variant of ALS, was diagnosed after extensive examinations ruling out other diseases. Due to supposed mercury exposure from residual amalgam, the patient's teeth were restored. Then, the patient received sodium 2,3-dimercaptopropanesulfate (DMPS; overall 86 × 250 mg in 3 years) in combination with α-lipoic acid and followed by selenium. In addition, he took vitamins and micronutrients and kept a vegetarian diet. The excretion of metals was monitored in the urine. The success of the therapy was followed by scoring muscle weakness and fasciculations and finally by electromyography (EMG) of the affected muscles. First improvements occurred after the dental restorations. Two months after starting therapy with DMPS, the mercury level in the urine was increased (248.4 µg/g creatinine). After 1.5 years, EMG confirmed the absence of typical signs of ALS. In the course of 3 years, the patient recovered completely. CONCLUSIONS: The therapy described here is a promising approach to treating some kinds of motor neuron disease and merits further evaluation in rigorous trials.


Assuntos
Esclerose Amiotrófica Lateral/induzido quimicamente , Esclerose Amiotrófica Lateral/terapia , Amálgama Dentário/química , Mercúrio , Esclerose Amiotrófica Lateral/tratamento farmacológico , Restauração Dentária Permanente , Exposição Ambiental , Humanos , Masculino , Mercúrio/urina , Pessoa de Meia-Idade , Atrofia Muscular Espinal/induzido quimicamente , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Muscular Espinal/terapia , Selênio/administração & dosagem , Ácido Tióctico/administração & dosagem , Resultado do Tratamento , Unitiol/administração & dosagem
19.
J Clin Pharm Ther ; 42(6): 783-785, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28635014

RESUMO

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.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Hemólise/efeitos dos fármacos , Degeneração Hepatolenticular/tratamento farmacológico , Unitiol/efeitos adversos , Unitiol/uso terapêutico , Adulto , Humanos , Masculino , Adulto Jovem
20.
J Clin Pharm Ther ; 42(4): 506-508, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28547870

RESUMO

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.


Assuntos
Intoxicação por Arsênico/tratamento farmacológico , Óxidos/envenenamento , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Unitiol/uso terapêutico , Adulto , Trióxido de Arsênio , Arsenicais , Quelantes/uso terapêutico , Feminino , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Tentativa de Suicídio , Resultado do Tratamento
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