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1.
Environ Toxicol ; 34(8): 921-927, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31066208

RESUMO

Hyperkalemia is often associated with cardiac dysfunction. In this study an earthworm extract (dilong) was prepared from dried Pheretima aspergillum powder and its effect against high-KCl challenge was determined in H9c2 cardiomyoblast cells. H9c2 cells pre-treated with dilong (31.25, 62.5, 125, and 250 mg/mL) for 24 hours, where challenged with different doses of KCl treatment for 3 hours to determine the protective mechanisms of dilong against cardiac fibrosis. High-KCl administration induced mitochondrial injury and elevated the levels of pro-apoptotic proteins. The mediators of fibrosis such as ERK, uPA, SP1, and CTGF were also found to be upregulated in high-KCl condition. However, dilong treatment enhanced IGF1R/PI3k/Akt activation which is associated with cell survival. In addition, dilong also reversed high-KCl induced cardiac fibrosis related events in H9c2 cells and displayed a strong cardio-protective effect. Therefore, dilong is a potential agent to overcome cardiac events associated with high-KCl toxicity.


Assuntos
Mitocôndrias Cardíacas/efeitos dos fármacos , Mioblastos Cardíacos/efeitos dos fármacos , Oligoquetos , Cloreto de Potássio/toxicidade , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Sobrevivência Celular , Fibrose , Mioblastos Cardíacos/patologia , Substâncias Protetoras/farmacologia
2.
Scand Cardiovasc J ; 52(6): 344-347, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30486695

RESUMO

OBJECTIVES: The aim of this study was to investigate how high K+ concentrations can be safely used in cardioplegic solutions without causing severe coronary artery vasocontraction. DESIGN: Twenty-four 50 kg pigs were used. The distal part of the left anterior descending coronary artery was cut into ring segments and transferred into organ baths with Krebs solution bubbled with 95% O2 and 5% CO2. K+ concentrations between 16 and 127 mM were used to induce vasocontractions at 37, 22, 15, and 8 °C. Mg2+ (0-20 mM) were used to attenuate K+ induced vasocontractions. RESULTS: K+-Krebs solution 127 mM at 37 °C induced a strong, sustained vasocontraction defined as 100%. The contractions induced by 16, 23, 30 and 127 mM K+ were: 7.7, 38, 72 and 100% at 37 °C; 1.7, 7.4, 21 and 65% at 22 °C; 1, 6.6, 15 and 33% at 15 °C; 0.6, 2.1, 6 and 14% at 8 °C, respectively. Mg2+ reduced the K+-induced contraction at 37 °C in a concentration-dependent way and Mg2+ at 8 mM practically eliminated the risk for severe vasocontraction. CONCLUSIONS: Hypothermia (8 °C) abolishes coronary contraction induced by K+-cardioplegic solutions. In normothermic cardioplegia 8 mM Mg2+ prevents vasoconstriction.


Assuntos
Soluções Cardioplégicas/toxicidade , Temperatura Baixa , Vasoespasmo Coronário/prevenção & controle , Vasos Coronários/efeitos dos fármacos , Hipotermia Induzida , Cloreto de Magnésio/farmacologia , Cloreto de Potássio/toxicidade , Vasoconstrição/efeitos dos fármacos , Animais , Vasoespasmo Coronário/induzido quimicamente , Vasoespasmo Coronário/fisiopatologia , Vasos Coronários/fisiopatologia , Relação Dose-Resposta a Droga , Técnicas In Vitro , Índice de Gravidade de Doença , Sus scrofa
3.
Environ Toxicol Chem ; 37(12): 3050-3062, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30129053

RESUMO

Freshwater mussels are generally underrepresented in toxicity databases used to derive water quality criteria, especially for long-term exposures. Multiple tests were conducted to determine the chronic toxicity of sodium chloride (NaCl) or potassium chloride (KCl) to a unionid mussel (fatmucket, Lampsilis siliquoidea). Initially, a 4-wk NaCl test and a 4-wk KCl test were conducted starting with 2-mo-old mussels in water exposures with and without a thin layer of sand substrate. A feeding study was conducted later to refine test conditions for longer-term 12-wk exposures, and 3 chronic NaCl tests were then conducted following the refined method to assess the influence of test duration (4-12 wk) and age of organisms (starting age ∼1 wk to 2 mo) on mussel sensitivity. Biomass (total dry wt of surviving mussels in a replicate) was generally a more sensitive endpoint compared to survival and growth (length and dry wt). In the 4-wk NaCl or KCl test started with 2-mo-old juveniles, a 20% effect concentration (EC20) based on biomass (264 mg Cl/L from the NaCl test or 8.7 mg K/L from the KCl test) in the exposure with sand was 2-fold lower than the EC20 in the exposure without sand. The longer-term 12-wk NaCl tests started with the 1-wk-old and 2-mo-old juveniles were successfully completed under refined test conditions based on the feeding study, and younger juveniles were more sensitive to NaCl than older juveniles. The NaCl toxicity did not substantially change with extended exposure periods from 4 to 12 wk, although the 4-wk EC20s for biomass were slightly greater (up to 37%) than the 12-wk EC20s in the 2 longer-term exposures. Including the toxicity data from the present study into existing databases would rank fatmucket the most sensitive species to KCl and the second most sensitive species to NaCl for all freshwater organisms. Environ Toxicol Chem 2018;37:3050-3062. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.


Assuntos
Bivalves/efeitos dos fármacos , Exposição Ambiental , Cloreto de Potássio/toxicidade , Cloreto de Sódio/toxicidade , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Padrões de Referência , Qualidade da Água
4.
Environ Toxicol Chem ; 37(12): 3041-3049, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29920756

RESUMO

Freshwater mussels (order Unionoida) are one of the most imperiled groups of animals in the world. However, many ambient water quality criteria and other environmental guideline values do not include data for freshwater mussels, in part because mussel toxicity test methods are comparatively new and data may not have been available when criteria and guidelines were derived. The objectives of the present study were to evaluate the acute toxicity of sodium chloride (NaCl) and potassium chloride (KCl) to larvae (glochidia) and/or juveniles of a unionid mussel (fatmucket, Lampsilis siliquoidea) and to determine the potential influences of water hardness (50, 100, 200, and 300 mg/L as CaCO3 ) and other major ions (Ca, K, SO4 , or HCO3 ) on the acute toxicity of NaCl to the mussels. From the KCl test, the 50% effect concentration (EC50) for fatmucket glochidia was 30 mg K/L, similar to or slightly lower than the EC50s for juvenile fatmucket (37-46 mg K/L) tested previously in our laboratory. From the NaCl tests, the EC50s for glochidia increased from 441 to 1597 mg Cl/L and the EC50s for juvenile mussels increased from 911 to 3092 mg Cl/L with increasing water hardness from 50 to 300 mg/L. Increasing K from 0.4 to 1.9 mg/L, SO4 from 13 to 40 mg/L, or HCO3 from 44 to 200 mg/L in the 50 mg/L hardness water did not substantially change the NaCl EC50s for juvenile mussels, whereas increasing Ca from 9.9 to 42 mg/L increased the EC50s by a factor of 2. The overall results indicate that glochidia were equally or more sensitive to NaCl and KCl compared with juvenile mussels and that the increased water hardness ameliorated the acute toxicity of NaCl to glochidia and juveniles. These responses rank fatmucket among the most acutely sensitive freshwater organisms to NaCl and KCl. Environ Toxicol Chem 2018;37:3041-3049. © 2018 SETAC. This article is a US government work and, as such, is in thepublic domain in the United States of America.


Assuntos
Bivalves/efeitos dos fármacos , Exposição Ambiental/análise , Cloreto de Potássio/toxicidade , Cloreto de Sódio/toxicidade , Testes de Toxicidade Aguda , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Íons , Larva/efeitos dos fármacos , Qualidade da Água
5.
J Aquat Anim Health ; 30(1): 3-12, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29595886

RESUMO

The use of chemicals to decontaminate watercraft and/or equipment after exposure to zebra mussels Dreissena polymorpha is one method of decontamination that has been recommended by multiple government agencies in the United States. The ideal chemical to be used for decontamination would be inexpensive and easily obtained, would have no or limited effect on nontarget species, and would be relatively environmentally friendly. Two chemicals that have been tested are potassium chloride (KCl) and sodium chloride (NaCl). The toxicity of each chemical to both adult zebra mussels and veliger larvae was examined. Sodium chloride was less effective at causing mortality than KCl within the exposure periods tested. Adult mussels required a 4× longer exposure period to exhibit complete mortality when exposed to NaCl at 30,000 mg/L (24 h) compared to KCl (6 h). At 10,000 mg/L, NaCl took 8× longer (96 h) than KCl (12 h) to cause 100% mortality of adult mussels. Veligers that were exposed to KCl at 1,250 mg/L required a 12-h exposure to attain complete mortality, while those exposed to NaCl at 10,000 mg/L required an 18-h exposure to exhibit the same result. To determine whether KCl is more advantageous as a decontamination chemical, the cost and chemical availability must be researched.


Assuntos
Dreissena/efeitos dos fármacos , Cloreto de Potássio/toxicidade , Cloreto de Sódio/toxicidade , Animais , Incrustação Biológica/prevenção & controle , Descontaminação/métodos , Larva/efeitos dos fármacos
6.
Chem Biodivers ; 14(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29139211

RESUMO

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16ß-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.


Assuntos
Alisma/química , Terpenos/química , 11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Alisma/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Extratos Vegetais/química , Cloreto de Potássio/toxicidade , Ratos , Rizoma/química , Rizoma/metabolismo , Terpenos/metabolismo , Terpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Difração de Raios X
8.
Sci Rep ; 7(1): 1311, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28465556

RESUMO

The random nature of seizures poses difficult challenges for epilepsy research. There is great need for a reliable method to control the pathway to seizure onset, which would allow investigation of the mechanisms of ictogenesis and optimization of treatments. Our hypothesis is that increased random afferent synaptic activity (i.e. synaptic noise) within the epileptic focus is one endogenous method of ictogenesis. Building upon previous theoretical and in vitro work showing that synaptic noise can induce seizures, we developed a novel in vivo model of ictogenesis. By increasing the excitability of afferent connections to the hippocampus, we control the risk of temporal lobe seizures during a specific time period. The afferent synaptic activity in the hippocampus was modulated by focal microinjections of potassium chloride into the nucleus reuniens, during which the risk of seizure occurrence increased substantially. The induced seizures were qualitatively and quantitatively indistinguishable from spontaneous ones. This model thus allows direct control of the temporal lobe seizure threshold via endogenous pathways, providing a novel tool in which to investigate the mechanisms and biomarkers of ictogenesis, test for seizure threshold, and rapidly tune antiseizure treatments.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Convulsões/fisiopatologia , Sinapses/efeitos dos fármacos , Lobo Temporal/fisiopatologia , Animais , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/induzido quimicamente , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Humanos , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/fisiopatologia , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/toxicidade , Ratos , Convulsões/induzido quimicamente , Sinapses/fisiologia
9.
Somatosens Mot Res ; 33(1): 35-41, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-27021138

RESUMO

We describe an animal model where characteristics of migraine can be triggered by alcohol administration. In rats chronically implanted with a cannula overlying the transverse sinus, we applied potassium chloride (KCl) (or saline) to the meninges to sensitize trigeminovascular afferents. We assessed effects of repeated KCl application on animal behavior using conditioned place avoidance paradigm. In KCl-treated rats we discovered that alcohol injections (0.2 mg/kg), but not saline, resulted in the development of extracephalic allodynia and signs of ongoing pain.


Assuntos
Álcoois/toxicidade , Transtornos de Enxaqueca/induzido quimicamente , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Hiperalgesia/etiologia , Masculino , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Cloreto de Potássio/toxicidade , Gravidez , Ratos , Ratos Sprague-Dawley
10.
Chemosphere ; 139: 597-603, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24932778

RESUMO

Criteria for establishing water quality standards that are protective for 95% of the native species are generally based upon laboratory toxicity tests. These tests utilize common model organisms that have established test methods. However, for invertebrates these species represent mostly the zooplankton community and are not inclusive of all taxa. In order to examine a potential under-representation in emerging aquatic invertebrates the US Environmental Protection Agency has cultured a parthenogenetic mayfly, Centroptilum triangulifer (Ephemeroptera: Baetidae). This study established a 48h acute and a 14-day short-term chronic testing procedure for C. triangulifer and compared its sensitivity to two model invertebrates, Ceriodaphnia dubia and Daphnia magna. Toxicity tests were conducted to determine mortality and growth effects using standard reference toxicants: NaCl, KCl and CuSO4. In 48-h acute tests, the average LC50 for the mayfly was 659mgL(-1) NaCl, 1957mgL(-1) KCl, and 11µgL(-1) CuSO4. IC25 values, using dry weight as the endpoint, were 228mgL(-1) NaCl, 356mgL(-1) KCl and 5µgL(-1) CuSO4. C. triangulifer was the most sensitive species in NaCl acute and chronic growth tests. At KCl concentrations tested, C. triangulifer was less sensitive for acute tests but was equally or more sensitive than C. dubia and D. magna for growth measurements. This study determined C. triangulifer has great potential and benefits for use in ecotoxicological studies.


Assuntos
Sulfato de Cobre/toxicidade , Daphnia/efeitos dos fármacos , Ephemeroptera/efeitos dos fármacos , Cloreto de Potássio/toxicidade , Cloreto de Sódio/toxicidade , Testes de Toxicidade/normas , Poluentes Químicos da Água/toxicidade , Animais , Padrões de Referência
11.
Bull Environ Contam Toxicol ; 93(4): 442-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25168694

RESUMO

The sensitivity of Danio rerio to three chemicals was compared at two growth stages [larval (10 ± 2 after hatching) and post-larval (60 ± 4 days after hatching)] based on acute toxicity tests. Thirty-nine 48 h acute toxicity tests were performed with the substances CuSO4, NaCl and KCl. The 48 h LC50 values at the two growth stages were compared by independent samples t-tests. The results showed a clear decrease in sensitivity when post-larval organisms were used. Since acute toxicity test methods for D. rerio that recommend using post-larval stage fish do not represent the most sensitive stage of the test organism, our study suggests a revision of the methods to use larval fish.


Assuntos
Sulfato de Cobre/toxicidade , Modelos Animais , Cloreto de Potássio/toxicidade , Cloreto de Sódio/toxicidade , Testes de Toxicidade Aguda/métodos , Peixe-Zebra/metabolismo , Fatores Etários , Animais , Larva/efeitos dos fármacos , Dose Letal Mediana
12.
Environ Toxicol Chem ; 33(1): 126-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24115165

RESUMO

Fathead minnows are routinely cultured for use in aquatic toxicology studies. A new mass culture system described in the present study consisted of 6 stainless steel tanks, each containing 68 fish and 20 spawning substrates. Spawning results are compared with a previous system of 22 individual glass aquaria, which contained 16 fish and 4 spawning substrates per tank. During a 19-mo period, the new system produced an average of 4105 eggs/d, compared with an average of 2465 eggs/d with the previous system. Labor and maintenance were reduced with the new system. The stainless steel tanks eliminated aquaria glass breakage, and daily water use was reduced by 45%. Analysis of reference toxicant data from fish cultured using both systems indicated no change in the sensitivity of the test animals. Analyses of 2009 egg production data determined that a 6:1 to 7:1 female to male ratio had a significantly positive impact on egg production levels and that 6-mo-old breeding stock should be introduced to the spawning tanks in mid-spring for optimal egg production during the rest of the year. Implementing a stainless steel mass culture system significantly increased efficiency of egg production; reduced turnaround delay of mature animal availability for toxicity and molecular testing; and reduced labor time, costs, and inherent safety hazards, compared with glass aquaria systems.


Assuntos
Cyprinidae/fisiologia , Testes de Toxicidade/instrumentação , Animais , Feminino , Laboratórios , Masculino , Modelos Animais , Oviparidade , Cloreto de Potássio/toxicidade , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade
13.
Transplant Proc ; 45(6): 2513-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23953572

RESUMO

BACKGROUND: NKG2D (natural killer group 2 member D), are activating or coactivating receptor on NK cells, γδ T, and CD8(+) T cells, stimulates cytokine secretion by the former two and plays a costimulatory role for the last CD8(+) T cells. METHODS: Male Lewis rat hearts were flushed and stored in cold Bretschneider preservation solution for 8 hours. Anti-NKG2D monoclonal antibody (mAb) was administered before transplantation into syngeneic recipients. Expressions of Troponin-T, myeloperoxidase (MPO), tumor necrosis factor (INF), (ICAM) and interleukin (IL)-17 were examined on days 1, 3, and 7 after reperfusion. RESULTS: We observed that isografts from anti-NKG2D mAb-treated animals showed decreased cardiac troponin-T, low expression of MPO, TNF, and ICAM, and superior cardiac output. Furthermore, blockade of NKG2D significantly reduced the number of γδ T cells, which are the main source of IL-17 production. CONCLUSION: Blockade of NKG2D significantly attenuated ischemia-reperfusion injury in a cardiac transplantation model. The effect coincided with a low expression of TNFα, ICAM and a reduced number of infiltrating IL-17-producing γδ T cells.


Assuntos
Anticorpos Monoclonais/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Transplante de Coração/efeitos adversos , Lectinas Tipo C/antagonistas & inibidores , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/antagonistas & inibidores , Animais , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Isquemia Fria/efeitos adversos , Citoproteção , Modelos Animais de Doenças , Glucose/toxicidade , Hemodinâmica/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-17/metabolismo , Lectinas Tipo C/metabolismo , Masculino , Manitol/toxicidade , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/imunologia , Miocárdio/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Soluções para Preservação de Órgãos/toxicidade , Peroxidase/metabolismo , Cloreto de Potássio/toxicidade , Procaína/toxicidade , Ratos , Ratos Endogâmicos Lew , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Recuperação de Função Fisiológica , Fatores de Tempo , Troponina T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Mar Drugs ; 11(8): 2873-81, 2013 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-23945599

RESUMO

The phylum Cnidaria is an ancient group of venomous animals, specialized in the production and delivery of toxins. Many species belonging to the class Anthozoa have been studied and their venoms often contain a group of peptides, less than 10 kDa, that act upon ion channels. These peptides and their targets interact with high affinity producing neurotoxic and cardiotoxic effects, and even death, depending on the dose and the administration pathway. Zoanthiniaria is an order of the Subclass Hexacorallia, class Anthozoa, and unlike sea anemone (order Actiniaria), neither its diversity of toxins nor the in vivo effects of the venoms has been exhaustively explored. In this study we assessed some toxicological tests on mice with a low molecular weight fraction obtained by gel filtration in Sephadex G-50 from Zoanthus sociatus crude extract. The gel filtration chromatogram at 280 nm revealed two major peaks, the highest absorbance corresponding to the low molecular weight fraction. The toxicological effects seem to be mostly autonomic and cardiotoxic, causing death in a dose dependent manner with a LD50 of 792 µg/kg. Moreover, at a dose of 600 µg/kg the active fraction accelerated the KCl-induced lethality in mice.


Assuntos
Antozoários/química , Toxinas Marinhas/toxicidade , Peptídeos/toxicidade , Animais , Cromatografia em Gel , Relação Dose-Resposta a Droga , Dose Letal Mediana , Masculino , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Camundongos , Peso Molecular , Peptídeos/isolamento & purificação , Cloreto de Potássio/toxicidade , Testes de Toxicidade
15.
J Exp Biol ; 215(Pt 24): 4237-41, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22996446

RESUMO

As scientific understanding of invertebrate life increases, so does the concern for how to end that life in an effective way that minimises (potential) suffering and is also safe for those carrying out the procedure. There is increasing debate on the most appropriate euthanasia methods for invertebrates as their use in experimental research and zoological institutions grows. Their popularity as pet species has also led to an increase in the need for greater veterinary understanding. Through the use of a local injection of potassium chloride (KCl) initially developed for use in American lobsters, this paper describes a safe and effective method for euthanasia in terrestrial invertebrates. Initial work focused on empirically determining the dose for cockroaches, which was then extrapolated to other arthropod species. For this method of euthanasia, we propose the term 'targeted hyperkalosis' to describe death through terminal depolarisation of the thoracic ganglia as a result of high potassium concentration.


Assuntos
Artrópodes/efeitos dos fármacos , Eutanásia Animal/métodos , Gânglios dos Invertebrados/efeitos dos fármacos , Cloreto de Potássio/administração & dosagem , Animais , Artrópodes/fisiologia , Gânglios dos Invertebrados/fisiologia , Injeções , Cloreto de Potássio/toxicidade
16.
PLoS One ; 7(3): e33002, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22427928

RESUMO

Previously, we have shown that the GABA synthesizing enzyme, L-glutamic acid decarboxylase 65 (GAD65) is cleaved to form its truncated form (tGAD65) which is 2-3 times more active than the full length form (fGAD65). The enzyme responsible for cleavage was later identified as calpain. Calpain is known to cleave its substrates either under a transient physiological stimulus or upon a sustained pathological insult. However, the precise role of calpain cleavage of fGAD65 is poorly understood. In this communication, we examined the cleavage of fGAD65 under diverse pathological conditions including rats under ischemia/reperfusion insult as well as rat brain synaptosomes and primary neuronal cultures subjected to excessive stimulation with high concentration of KCl. We have shown that the formation of tGAD65 progressively increases with increasing stimulus concentration both in rat brain synaptosomes and primary rat embryo cultures. More importantly, direct cleavage of synaptic vesicle - associated fGAD65 by calpain was demonstrated and the resulting tGAD65 bearing the active site of the enzyme was detached from the synaptic vesicles. Vesicular GABA transport of the newly synthesized GABA was found to be reduced in calpain treated SVs. Furthermore, we also observed that the levels of tGAD65 in the focal cerebral ischemic rat brain tissue increased corresponding to the elevation of local glutamate as indicated by microdialysis. Moreover, the levels of tGAD65 was also proportional to the degree of cell death when the primary neuronal cultures were exposed to high KCl. Based on these observations, we conclude that calpain-mediated cleavage of fGAD65 is pathological, presumably due to decrease in the activity of synaptic vesicle - associated fGAD65 resulting in a decrease in the GABA synthesis - packaging coupling process leading to reduced GABA neurotransmission.


Assuntos
Encéfalo/metabolismo , Calpaína/metabolismo , Glutamato Descarboxilase/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Animais , Calpaína/farmacologia , Microdiálise , Cloreto de Potássio/toxicidade , Ratos , Traumatismo por Reperfusão/metabolismo , Sinaptossomos/metabolismo
17.
Cephalalgia ; 31(16): 1601-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22013142

RESUMO

BACKGROUND: Migraine is a disabling chronic episodic disorder. Attack frequency progressively increases in some patients. Incremental cortical excitability has been implicated as a mechanism underlying progression. Cortical spreading depression (CSD) is the electrophysiological event underlying migraine aura, and a headache trigger. We hypothesized that CSD events during frequent migraine attacks condition the cortex to increase the susceptibility to further attacks. METHODS: A single daily CSD was induced for 1 or 2 weeks in mouse frontal cortex; contralateral hemisphere served as sham control. At the end of CSD conditioning, occipital CSD susceptibility was determined by measuring the frequency of CSDs evoked by topical KCl application. RESULTS: Sham hemispheres developed 8.4 ± 0.3 CSDs/hour, and did not significantly differ from naïve controls without prior cranial surgery (9.3 ± 0.4 CSDs/hour). After 2 but not 1 week of daily CSD conditioning, CSD frequency (4.9 ± 0.3 CSDs/hour) as well as the duration and propagation speed were reduced significantly in the conditioned hemispheres. Histopathological examination revealed marked reactive astrocytosis without neuronal injury throughout the conditioned cortex after 2 weeks, temporally associated with CSD susceptibility. CONCLUSIONS: These data do not support the hypothesis that frequent migraine attacks predispose the brain to further attacks by enhancing tissue susceptibility to CSD.


Assuntos
Encéfalo/fisiopatologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Enxaqueca com Aura/fisiopatologia , Animais , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Enxaqueca com Aura/induzido quimicamente , Cloreto de Potássio/toxicidade
18.
Clin Toxicol (Phila) ; 49(5): 436-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21740145

RESUMO

This report contains images and a summary of a 31-year-old male patient who presented with skin lesions after subcutaneous injection of potassium chloride in an attempted suicide. Both forearms showed formation of vesicles with purple necrotic changes. Escharotomy, debridement, artificial skin graft, and local flap surgery were performed during hospitalization. This report includes images illustrating the course of the chemical burn due to subcutaneous injection of potassium chloride, and a brief review.


Assuntos
Queimaduras Químicas/etiologia , Cloreto de Potássio/toxicidade , Adulto , Queimaduras Químicas/terapia , Humanos , Injeções Subcutâneas , Masculino , Cloreto de Potássio/administração & dosagem
19.
Actas Urol Esp ; 35(5): 253-8, 2011 May.
Artigo em Espanhol | MEDLINE | ID: mdl-21440955

RESUMO

PURPOSE: The aim of this study is to develop a new experimental model of inducing interstitial cystitis (IC) through vesical instillation of a polymeric solution containing the NO donor S-nitrousglutathione (GSNO) and to compare it to the experimental interstitial cystitis induced by vesical instillation of protamine and potassium chloride. MATERIAL AND METHOD: For that purpose 40 female Wistar rats were used, divided in four groups: 1. saline solution + GSNO; 2. saline solution + polymeric solution (without GNSO); 3. protamine sulphate + KCl; 4. protamine sulphate + GSNO. The rats received one application (5 animals) or 3 applications (5 animals) of the corresponding substance through intravesical instillation, and after 6 days (5 animals) or 9 days (5 animals) they were euthanized and their bladders were removed for macroscopic evaluation and histological study. RESULTS: In the macroscopic evaluation we observed edema and hyperemia of the mucosa in 2 (22%) of the animals in group 1, in 0 (0%) of the animals in group 2, in 10 (100%) of the animals in group 3, and in 5 (50%) of the animals in group 4. In the protamine + KCl group and in saline + GSNO similar effects were observed on the bladder wall. The animals in group 2 (saline + polymeric) showed vascular congestion, significantly smaller than the rest after 9 days instillations (p=0.0035). Significant increased fibrosis was observed after instillations in groups 3 and 4, after 6 days (p=0.3781) and 9 days (p=0.0459) respectively, when compared to control (group 2). All groups presented neutrophilic infiltrate of variable intensity 6 days after instillations (p=0.7277). After 9 days, there was a regression of the infiltrate, with no evidence of accentuated neutrophilic reaction in all the groups (p=0.2301). CONCLUSION: The inflammatory response to bladder instillation of an aqueous solution of S-nitrousglutathione was very similar to that induced by bladder instillation of protamine and KCl. Instillation of an aqueous solution of GSNO can be considered a new model for experimental induction of interstitial cystitis.


Assuntos
Cistite Intersticial/induzido quimicamente , Modelos Animais de Doenças , Glutationa/análogos & derivados , Doadores de Óxido Nítrico/toxicidade , Nitrocompostos/toxicidade , Administração Intravesical , Animais , Quimiotaxia de Leucócito/efeitos dos fármacos , Cistite Intersticial/patologia , Edema/induzido quimicamente , Edema/patologia , Feminino , Géis , Glutationa/administração & dosagem , Glutationa/toxicidade , Hiperemia/induzido quimicamente , Hiperemia/patologia , Instilação de Medicamentos , Neutrófilos/patologia , Doadores de Óxido Nítrico/administração & dosagem , Nitrocompostos/administração & dosagem , Estresse Oxidativo , Veículos Farmacêuticos , Polietilenoglicóis , Cloreto de Potássio/toxicidade , Propilenoglicóis , Protaminas/toxicidade , Ratos , Ratos Wistar
20.
Bull Exp Biol Med ; 152(2): 177-9, 2011 Dec.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-22808453

RESUMO

Experiments on Wistar rats showed that exenatide (0.015-0.5 nmol per 100 g body weight) somewhat increased renal excretion of potassium from 7±1 to 16±1 µmol/h/100 g body weight (p<0.05) in animals with normal serum concentration of glucose (4.6±0.4 mM) and potassium (4.3±0.1 mM). Exenatide dramatically enhanced excretion of potassium under conditions of hyperkalemia (11.4±0.4 mM) produced by intraperitoneal injection of 1.25% KCl solution (5 ml per 100 g body weight). During the first postinjection hour, potassium excretion increased 2-fold and attained 97±11 µmol/h/100 g body weight in comparison with potassium load alone (47±9 µmol/h/100 g body weight, p<0.05). The data attest to a possible role of peptide regulators in normalization of potassium balance via renal mechanisms.


Assuntos
Hiperpotassemia/tratamento farmacológico , Peptídeos/uso terapêutico , Potássio/metabolismo , Peçonhas/uso terapêutico , Animais , Exenatida , Feminino , Hiperpotassemia/induzido quimicamente , Rim/efeitos dos fármacos , Rim/metabolismo , Cloreto de Potássio/toxicidade , Ratos , Ratos Wistar
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