RESUMO
The concern regarding the harm caused by biocides to human health has been increasing over the years, making the natural products an alternative to less toxic and more efficient biocides. Therefore, this paper reports the investigation of the disinfectant potential of extracts and isolated compounds from Baccharis dracunculifolia. For this purpose, extracts of aerial parts (BD-C), tricomial wash (BD-L) and roots (BD-R) of B. dracunculifolia were obtained by maceration. The extracts were submitted to different chromatographic techniques, including high-speedy countercurrent chromatography (HSCCC) furnishing nine isolated compounds. The extracts and isolated compounds were evaluated regarding their antimicrobial activity by the broth microdilution method, according to the Clinical and Laboratory Standards Institute, and regarding their sanitizing activity according to Standard Operating Procedure No. 65·3210·007 (INCQS, 2011), developed by the National Institute for Quality Control in Health (INCQS) - Oswaldo Cruz Foundation (FIOCRUZ). In the antimicrobial evaluation the BD-C extract showed minimum inhibitory concentration (MIC) values of 200 and 100 µg/ml against Staphylococcus aureus and Tricophyton mentagrophytes, respectively. BD-L extract showed MIC value of 200 µg/ml against S. aureus. The isolated compounds caffeic acid (MBC 2·22 µmol l-1 ), ferulic acid (MBC 2·06 µmol l-1 ) and baccharin (MBC 0·27 µmol l-1 ) showed significant inhibitory activity against S. aureus. All B. dracunculifolia isolated compounds were active with exception of aromadrendin-4´-O-methyl-ether for T. mentagrophytes. Additionally, isosakuranetin was active against Salmonella choleraesuis (MIC 1·4 µmol l-1 ). Regarding the sanitizing activity, the hydroalcoholic solution containing 0·2% of B. dracunculifolia extract in 40°GL ethanol was effective in eliminating the microbial contamination on all carrier cylinders and against all microorganisms evaluated in the recommended exposure time of 10 min. Therefore, B. dracunculifolia has potential for the development of sanitizing agents to be used in hospitals, food manufactures and homes.
Assuntos
Anti-Infecciosos , Baccharis , Desinfetantes , Anti-Infecciosos/farmacologia , Baccharis/química , Desinfetantes/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Staphylococcus aureusRESUMO
Energy advancement and innovation have generated several challenges for large modernized cities, such as the increase in energy demand, causing the appearance of the small power grid with a local source of supply, called the Microgrid. A Microgrid operates either connected to the national centralized power grid or singly, as a power island mode. Microgrids address these challenges using sensing technologies and Fog-Cloudcomputing infrastructures for building smart electrical grids. A smart Microgrid can be used to minimize the power demand problem, but this solution needs to be implemented correctly so as not to increase the amount of data being generated. Thus, this paper proposes the use of Fog computing to help control power demand and manage power production by eliminating the high volume of data being passed to the Cloud and decreasing the requests' response time. The GridLab-d simulator was used to create a Microgrid, where it is possible to exchange information between consumers and generators. Thus, to understand the potential of the Fog in this scenario, a performance evaluation is performed to verify how factors such as residence number, optimization algorithms, appliance shifting, and energy sources may influence the response time and resource usage.
RESUMO
In this work, we have found complete water miscibility for a priori, water immiscible (highly hydrophobic) ionic liquids by chemical manipulation of the quaternary ammonium cation grafted with hydroxyethyl moieties. Specifically, we were able to obtain bistriflimide-based ionic liquids completely miscible with water, even below room temperature. The underlying reason is the full integration of the OH groups of the cation in the continuous H-bonded network of water.
RESUMO
Indigenous patient navigator (IPN) programmes show promise in addressing barriers to cancer care and facilitation of patient self-efficacy. The purpose of this paper is to describe and reflect upon the experience of training an IPN and implementation of the intervention in the Australian context with Indigenous cancer patients. Randomised clinical trial might provide the best available evaluation measure of an intervention but caution should be taken in the implementation process. Socio-cultural aspects and training can affect the conduct of this type of intervention. We report here five issues needing consideration prior to implementing such intervention. Specifically: (1) recognition of the collective bonds within Indigenous community and understanding by IPN of the degree of personal assistance perceived as not intrusive by the patient; (2) conduct ongoing evaluation of the different role of an IPN involved in this intervention care provider vs. researcher. (3) meaningful engagement develops from a trusting/collaborative relationship between research team and study site staff which may not occur in the study time frame; (4) existing skills as well as training provided may not translate in the IPN understanding and aligning with the study objectives/research values; (5) recruitment of participants requires innovative and highly flexible strategies to be successful.
Assuntos
Havaiano Nativo ou Outro Ilhéu do Pacífico , Neoplasias , Navegação de Pacientes , Competência Cultural , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Projetos Piloto , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Queensland , Pesquisa , Papel (figurativo) , AutoeficáciaRESUMO
PURPOSE: The purpose of this study was to explore Indigenous Australian cancer survivors' perspectives of follow-up cancer care and management.. METHODS: This is a qualitative study employing individual interviews with 21 Indigenous cancer survivors (13 females, 8 males) recruited from a rural primary health service and large tertiary hospital in Brisbane, Queensland. Yarning methods were used to conduct semi-structured interviews. Yarning is a culturally appropriate, informal conversational process emphasising the importance of storytelling. RESULTS: Findings describe a range of ways in which follow-up cancer care is experienced with four major categories elucidated, namely: links to tertiary health services, links to primary health services, communication between tertiary and primary health services, and lost in transition. Both positive and negative experiences were described; however, the importance of timely and informative discharge information, continuity of care, good communication between tertiary and primary health services, and strong therapeutic relationships were salient issues raised by participants. CONCLUSIONS: These findings highlight the importance of establishing strong therapeutic relationships between patients and tertiary and primary health professionals. Also important for survivorship is provision of discharge summaries or care plans at discharge for survivors and general practitioners as well as access to a range of allied health services. Alternative means for follow-up could be investigated for regional and rural survivors to facilitate convenient and cost-effective follow-up care. Finally, provision of responsive and flexible follow-up care to cater for the diverse range of needs and preferences of cancer survivors is required. A patient navigator available across the cancer continuum could go some way to addressing this.
Assuntos
Neoplasias/etnologia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Feminino , Seguimentos , Serviços de Saúde do Indígena , Humanos , Masculino , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico , Neoplasias/mortalidade , Pesquisa Qualitativa , Sobreviventes , Adulto JovemAssuntos
Colite/induzido quimicamente , Colite/patologia , Imidazóis/efeitos adversos , Tetrazóis/efeitos adversos , Cápsulas Endoscópicas , Colite/diagnóstico por imagem , Colo/diagnóstico por imagem , Colo/patologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Little is known about the supportive care needs (SCN) of Australian Indigenous cancer patients. This cross-sectional study investigated the association between comorbidity and SCN among newly diagnosed Indigenous cancer patients in Queensland. Comorbidity was ascertained from medical chart review using the Charlson Comorbidity Index (CCI) and SCN were measured using the Supportive Care Needs Assessment Tool for Indigenous Peoples (SCNAT-IP). Of 183 participants, 76 (42%) had no comorbidity (CCI = 0), 60 (33%) had had a CCI score of 1 and 47 (26%) had a CCI of two or more, with the most common condition being diabetes (30%). The most common moderate-high unmet need items varied between comorbidity groups, although all patients most frequently reported moderate-high unmet need in the Physical and Psychological and the Practical and Cultural needs domains. Patients with the greatest comorbidity (CCI ≥ 2) had significantly more reduced odds of practical and cultural needs than patients without comorbidity (OR 0.28, 95% CI 0.11-0.75). This appeared to be partially explained by time since diagnosis, age, whether they were receiving current treatment and residential remoteness. Patients' experience of chronic disease, hospitals and the healthcare system may better prepare them for the practical and cultural aspects of their cancer journey.
Assuntos
Atividades Cotidianas , Comunicação , Necessidades e Demandas de Serviços de Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico , Neoplasias/terapia , Educação de Pacientes como Assunto , Apoio Social , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Comorbidade , Estudos Transversais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Neoplasias/epidemiologia , Queensland , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/terapiaRESUMO
PCR screening of ticks and tissue samples collected from 151 Teira dugesii lizards seems to indicate a potential role of this lizard species in the maintenance and transmission cycle of some Ixodes ricinus tick-borne agents, such as Rickettsia monacensis, Rickettsia helvetica, and Borrelia lusitaniae, that are circulating on Madeira Island.
Assuntos
Anaplasma phagocytophilum/isolamento & purificação , Borrelia/isolamento & purificação , Reservatórios de Doenças , Ixodes/microbiologia , Lagartos/microbiologia , Rickettsia/isolamento & purificação , Doenças Transmitidas por Carrapatos/transmissão , Anaplasma phagocytophilum/genética , Animais , Técnicas Bacteriológicas , Borrelia/genética , Lagartos/parasitologia , Reação em Cadeia da Polimerase , Rickettsia/genéticaRESUMO
The aim of the present study was to investigate the effects of resistance training on glycogen content and muscle cross-sectional area (CSA) in ovariectomized rats. Wistar rats were divided into: sedentary; ovariectomized sedentary; resistance trained; and ovariectomized resistance trained. In the 12-week resistance training, the animals climbed a 1.1 m vertical ladder, 3 days per week, with 4-8 climbs. Cardiac, liver and muscle glycogen content was determined. After the 12-week resistance training period there was a higher hepatic and muscle glycogen content in the resistance training group compared with the other groups (p<0.01). CSA was higher in soleus for the resistance trained, ovariectomized resistance trained and sedentary compared with ovariectomized sedentary (p<0.05). Ovariectomy attenuated the increase in liver and muscle glycogen content, while soleus muscle cross-sectional area increased with resistance training, even in ovariectomized rats. Resistance training could be an important exercise to increase muscle function in situations of reduced estrogen and progesterone.
Assuntos
Glicogênio/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Feminino , Fígado/metabolismo , Miocárdio/metabolismo , Ovariectomia , Ratos , Ratos Wistar , Treinamento ResistidoRESUMO
AIM: The aim of the present study was to evaluate the effects of 16 weeks of periodized resistance training in lipid profile in sedentary middle-aged men and women. METHODS: Healthy subjects (N.=50), middle-aged men and postmenopausal women (>12 months amenorrhea), were randomized into resistance training men (RTM), resistance training women (RTW), control group men (CGM) and control group women (CGW). They performed three weekly sessions for 16 weeks (9 exercises with 3 x 8-10 RM and with a 60-90 seconds rest period). RESULTS: Trained groups showed significant decrease in total cholesterol (TC) (RTM -23.61%; RTW -21.08%; P=0.0001) and LDL-C (RTM -35.68%; RTW -38.53%; P=0.0001). No significant changes were observed in HDL-C and triglycerides (TG). No significant changes were found in plasma levels of LDL-C, HDL-C and TG for control groups, though there were significant differences between CGM and CGW for TC. CONCLUSION: The present results indicate that 16 weeks of periodized RT contribute to decrease of cardiovascular risk factors, such as LDL-C and TC in middle-aged men and women, even without changes in body mass and body mass index.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipídeos/sangue , Treinamento Resistido/métodos , Análise de Variância , Antropometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Pós-Menopausa , Fatores de Risco , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
The aim of this study was to analyze the effects of chronic mild unpredictable stress (CMS) on the vasoconstrictor response and morphology of the thoracic aorta and serum lipid profiles in rats. Male Sprague-Dawley rats were submitted to CMS, which consisted of the application of different stressors for 7 days per week across 3 weeks. The rats were sacrificed 15 days after CMS exposure. CMS induced supersensitivity to the vasoconstrictor effect of phenylephrine in endothelium-intact thoracic aortic rings without changes in aortic rings without endothelium, or pre-incubated with nitric oxide (NO) synthesis inhibitor. Rats submitted to CMS showed hypertrophy of the intima and tunica media of thoracic aorta, increased serum levels of triglycerides, total cholesterol, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and atherogenic index, without changes in high-density lipoprotein cholesterol levels, when compared with control rats. These data indicate that CMS induces physiological and morphological changes that may contribute to the development of atherosclerosis by mechanisms related to deficiency in NO production and dyslipidemia.
Assuntos
Aorta Torácica/efeitos dos fármacos , Aterosclerose/psicologia , Fenilefrina/farmacologia , Estresse Psicológico/fisiopatologia , Vasoconstritores/farmacologia , Animais , Aorta Torácica/enzimologia , Aorta Torácica/patologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Corticosterona/sangue , Lipídeos/sangue , Masculino , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
During decades, mercury (Hg) was discharged into the Aveiro Lagoon. Twenty-five years after the cessation of discharges, sediment cores were collected at two areas to assess the evolution of the mercury contamination status. Vertical Hg profiles differed considerably between bare and vegetated sediments. Bare sediments contained significantly less Hg (<8â¯mgâ¯kg-1) than historical data of 1995 (up to 40â¯mgâ¯kg-1), probably resulting from erosion. Salt marsh sediments were marked by a Hg sub-surface enrichment, reaching 44â¯mgâ¯kg-1 in the site closer to the industrial discharge point. High Hg concentrations in 2007, 2011 and 2016 were found at similar sediment layers. These results emphasise the role of halophyte plants in the cycling and retention of Hg in sediments. The persistency of high Hg in the upper marsh layers highlights the complexity in the recovery of historically contaminated marshes and the vulnerability to modifications in hydrology associated with climate changes.
Assuntos
Sedimentos Geológicos/análise , Mercúrio/análise , Poluentes Químicos da Água/análise , Áreas Alagadas , Biodegradação Ambiental , Chenopodiaceae/fisiologia , Monitoramento Ambiental , Portugal , Plantas Tolerantes a SalRESUMO
The high prevalence of exercise-induced pulmonary hemorrhage (EIPH) in athletic horses constitutes to be a challenge to the racing industry and a source of major concern to animal welfare. Both experimental and clinical evidence indicate that the use of autologous platelet-rich plasma (PRP) is a promising effector of repair in a variety of pulmonary conditions. The present study evaluated the effect of intrabronchial instillation of PRP on EIPH endoscopic scores from 37 Thoroughbred racehorses. Inclusion criteria were for animals to be EIPH-positive in, at least, two consecutive post-exercise endoscopic exams and to receive 250mg of furosemide IV four hours before racing. Animals were randomly assigned into 3 groups: placebo, control, and PRP instillation. All 37 Thoroughbred racehorses included had EIPH endoscopic scores pre- and post- treatment compared by statistical analysis. The bleeding score from the group receiving PRP was significantly lower than in the control and placebo groups. No adverse effects were observed in any animal during or after the experiment. It was possible to conclude that the intrabronchial instillation of autologous PRP was effective in reducing EIPH scores in racehorses receiving furosemide and that this bioproduct can be considered as a promising coadjuvant in controlling EIPH in athletic horses.(AU)
A alta prevalência de hemorragia pulmonar induzida por exercício (HPIE) em cavalos atletas é um desafio de longa data para a indústria de corridas, além de figurar como grande preocupação sobre o bem-estar animal. As evidências experimentais e clínicas indicam que o uso do plasma rico em plaquetas (PRP) de fonte autógena é promissor na terapêutica de diversas lesões pulmonares. O presente estudo objetivou avaliar as mudanças após corrida no escore endoscópico de HPIE de 37 cavalos Puro-Sangue Inglês que receberam instilação intrabronquial de PRP autólogo. Os animais selecionados eram HPIE-positivos em, ao menos, dois exames endoscópicos consecutivos e recebiam 250mg de furosemida IV administrado quatro horas antes de cada corrida. Na comparação dos escores endoscópicos pré e pós-tratamento, verificou-se que o escore de HPIE do grupo tratado com PRP foi significantemente menor que o dos grupos controle e placebo. Nenhum efeito adverso foi observado nos animais durante ou após o experimento. Concluiu-se que a instilação intrabronquial de PRP autólogo foi efetiva na redução do escore de HPIE de cavalos de corrida usuários de furosemida e que este bioproduto pode ser considerado uma alternativa promissora no controle de HPIE em cavalos atletas.(AU)
Assuntos
Animais , Condicionamento Físico Animal/efeitos adversos , Plasma Rico em Plaquetas , Lesão Pulmonar Aguda/veterinária , Cavalos/fisiologia , Instilação de Medicamentos , Furosemida/análise , Hemorragia/veterináriaRESUMO
Isolated rat liver mitochondria, energized either by succinate oxidation or by ATP hydrolysis, present a transient increase in the rate of Ca2+ efflux concomitant to NAD(P)H oxidation by hydroperoxides when suspended in a medium containing 3 mM ATP, 4 mM Mg2+ and acetate as permeant anion. This is paralleled by an increase in the steady-state concentration of extramitochondrial Ca2+, a small decrease in delta psi and an increase in the rate of respiration and mitochondrial swelling. With the exception of mitochondrial swelling all other events were found to be reversible. If Ca2+ cycling was prevented by ruthenium red, the changes in delta psi, the rate of respiration and the extent of mitochondrial swelling were significantly diminished. In addition, there was no significant decrease in the content of mitochondrial pyridine nucleotides. Mitochondrial coupling was preserved after a cycle of Ca2+ release and re-uptake under these experimental conditions. It is concluded that hydroperoxide-induced Ca2+ efflux from intact mitochondria is related to the redox state of pyridine nucleotides.
Assuntos
Trifosfato de Adenosina/farmacologia , Antiporters , Cálcio/metabolismo , Proteínas de Transporte de Cátions , Magnésio/farmacologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Peróxidos/farmacologia , Acetoacetatos/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Canais de Cálcio , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Fluorescência , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Potenciais da Membrana , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/ultraestrutura , NADP/metabolismo , Oxirredução , Consumo de Oxigênio , Ratos , Ratos Endogâmicos , terc-Butil HidroperóxidoRESUMO
African swine fever virus (ASFV) enters cells by receptor mediated endocytosis and requires a fusion event between the viral envelope and the limiting membrane of the endosome at low pH. In order to investigate the role of cholesterol in the early stages of ASFV infection, we have studied the effect of the removal of cell and viral membrane cholesterol by cholesterol oxidase treatment of cells and virions, as well as the effect of some inhibitors of cholesterol synthesis on the infectious pathway. In addition, we have investigated viral infection in cholesterol-depleted Vero cells. Both cholesterol-depleted and cholesterol oxidase-treated Vero cells were unaltered in their ability to bind or internalize the virus, but were blocked in ASFV fusion and subsequent virus replication. Our results indicate that ASFV infection is affected by cholesterol in the target membrane.
Assuntos
Vírus da Febre Suína Africana/metabolismo , Membrana Celular/metabolismo , Colesterol/metabolismo , Febre Suína Africana/metabolismo , Animais , Membrana Celular/virologia , Cerulenina/farmacologia , Chlorocebus aethiops , Colesterol Oxidase/farmacologia , Miconazol/farmacologia , Sulfonamidas/farmacologia , Células VeroRESUMO
We have recently shown that the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants is associated with oxidation of protein thiols forming cross-linked protein aggregates (Fagian, M.M., Pereira-da-Silva, L., Martins, I.S. and Vercesi, A.E. (1990) J. Biol. Chem. 265, 19955-19960). In this study we show that the incubation of rat liver mitochondria in the presence of the thiol reagent 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and Ca2+ caused production of membrane protein aggregates, mitochondrial swelling, disruption of membrane potential and Ca2+ release. The presence of DTT prevented but did not reverse the elimination of delta psi induced by DIDS. EGTA prevented delta psi elimination and decreased the amount of protein aggregates, suggesting that the binding of Ca2+ to some membrane protein may expose buried thiols to react with DIDS. Reversal of collapsed delta psi by EGTA indicates that DIDS-induced protein aggregates require the presence of Ca2+ for significant membrane permeabilization. Cyclosporin A prevented mitochondrial swelling, suggesting that DIDS-induced membrane protein polymerization mimics the condition designated as Ca(2+)-induced permeabilization transition of mitochondria. The lack of oxidation of pyridine nucleotides or significant lipid peroxidation by DIDS supports the notion that membrane permeabilization by this compound is mediated by its interaction with membrane proteins.
Assuntos
Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Cálcio/farmacologia , Membranas Intracelulares/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Animais , Cálcio/metabolismo , Ditiotreitol , Ácido Egtázico , Membranas Intracelulares/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , NADP/metabolismo , Permeabilidade/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Trypanosoma cruzi epimastigotes maintained an intracellular free calcium concentration of about 0.15 microM, as measured with the fluorescent indicator Fura-2. The maintenance of low [Ca2+]i is energy-dependent since it is disrupted by KCN and FCCP. When the cells were permeabilized with digitonin, the steady-state free Ca2+ concentration in the absence of ATP was about 0.7 microM. The additional presence of ATP resulted in a steady-state level close to 0.1-0.2 microM which compares favorably with the concentration detected in intact cells. Intracellular Ca2+ uptake at high levels of free Ca2+ (greater than 1 microM) was due to energy-dependent mitochondrial uptake as indicated by its FCCP-sensitivity. However, as the free Ca2+ concentration was lowered from 1 microM, essentially all uptake was due to the ATP-dependent Ca2+ sequestration by the endoplasmic reticulum as indicated by its stimulation by ATP, and its inhibition by sodium vanadate. High concentrations of the calmodulin antagonist trifluoperazine, inhibited both the Ca2+ uptake by the endoplasmic reticulum and by the mitochondria, while calmidazolium released Ca2+ from both compartments. In addition, trifluoperazine and calmidazolium inhibited respiration and collapsed the mitochondrial membrane potential of T. cruzi, thus indicating non-specific effects unrelated to calmodulin.
Assuntos
Cálcio/metabolismo , Calmodulina/antagonistas & inibidores , Imidazóis/farmacologia , Trifluoperazina/farmacologia , Trypanosoma cruzi/metabolismo , Animais , Transporte Biológico , Permeabilidade da Membrana Celular/efeitos dos fármacos , Citosol/metabolismo , Homeostase/efeitos dos fármacos , Potenciais da Membrana , Oxigênio/metabolismo , Espectrometria de Fluorescência , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Cell viability requires the perfect functioning of the processes controlling ATP and Ca(2+) homeostasis. It is known that cell death caused by a variety of toxins or pathological conditions is associated with a disruption of ATP and Ca(2+) homeostasis. This study shows that 4,4'-diisothyocyanatostilbene-2,2'-disulfonic acid (DIDS) inhibits Trypanosoma cruzi epimastigote cell growth. This thiol-reagent thiocyanate derivative was able to inhibit two ecto-enzymes present in this parasite. The ecto-ATPase and ecto-phosphatase activities were inhibited in a dose-dependent manner (K(i)=47.7 and 472.5 microM, respectively), but the 5'nucleotidase and 3'nucleotidase activities were not. DIDS uptake was approached by fluorescence microscopy. Pulse-chase experiments revealed the DIDS accumulation in compartments, presumably endocytic, in the posterior region of epimastigotes. In addition, we show that the T. cruzi mitochondria studied in permeabilized cells are able to accumulate and retain medium Ca(2+) in the absence of DIDS. However, in the presence of increasing concentrations of DIDS (50-200 microM), Ca(2+) transport was inhibited in a dose-dependent manner. DIDS also caused a disruption of the mitochondrial membrane potential, in the same concentration range, thus explaining its effect on Ca(2+) uptake. The presence of EGTA prevented the elimination of the mitochondrial membrane potential (DeltaPsi), supporting previous data suggesting that the binding of Ca(2+) to the mitochondrial membrane exposes buried thiols to react with DIDS. This thiocyanate derivative was also able to inhibit Ca(2+) uptake by the endoplasmic reticulum in a dose-dependent manner. Taken together, the data presented here provide further insights into the mechanisms underlying the antiproliferative actions of DIDS in T. cruzi.
Assuntos
Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Cálcio/metabolismo , Trypanosoma cruzi/efeitos dos fármacos , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacocinética , Adenosina Trifosfatases/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Animais , Transporte Biológico , Carbonil Cianeto p-Trifluormetoxifenil Hidrazona/farmacologia , Divisão Celular/efeitos dos fármacos , Digitonina/farmacologia , Relação Dose-Resposta a Droga , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Homeostase/efeitos dos fármacos , Membranas Intracelulares/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Permeabilidade/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/metabolismoRESUMO
Age-related changes in the modulatory action of nitric oxide (NO) on cyclic GMP levels and Na(+),K(+)-ATPase activity in the proximal rat trachea were investigated using sodium nitroprusside, 8-bromo-cyclic GMP and okadaic acid. At 24 months, both control activities of Na(+), K(+)-ATPase and Mg(2+)-ATPase were decreased when compared to the segments from 4- and 12-month-old animals. However, cyclic GMP levels were similar among the three ages. Sodium nitroprusside (100 microM) induced stimulation of Na(+),K(+)-ATPase activity in segments from both 4- and 12-month-old animals, but not 24-month-old animals. The effect was specific for Na(+),K(+)-ATPase since Mg(2+)-ATPase activity was unaffected. Sodium nitroprusside induced an increase in nitrates/nitrites and cyclic GMP levels in proximal segments at 4, 12 and 24 months. The 8-bromo-cyclic GMP (100 microM) induced a similar specific stimulation of Na(+),K(+)-ATPase activity in segments from 4- and 12- but not 24-month-old animals. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na(+), K(+)-ATPase but not Mg(2+)-ATPase activity in tissues from 4-, 12- and 24-month-old animals. Our results suggest that aging affects cyclic GMP pathway in proximal rat trachea by an action at the level of the cyclic GMP-dependent protein kinase.
Assuntos
Envelhecimento/fisiologia , GMP Cíclico/fisiologia , Óxido Nítrico/fisiologia , ATPase Trocadora de Sódio-Potássio/fisiologia , Traqueia/fisiologia , Animais , ATPase de Ca(2+) e Mg(2+)/antagonistas & inibidores , ATPase de Ca(2+) e Mg(2+)/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , GMP Cíclico/farmacologia , Inibidores Enzimáticos/farmacologia , Indicadores e Reagentes , Masculino , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitritos/metabolismo , Nitroprussiato/farmacologia , Ácido Okadáico/farmacologia , Fosfoproteínas Fosfatases/antagonistas & inibidores , Proteína Fosfatase 1 , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Traqueia/efeitos dos fármacos , Traqueia/metabolismoRESUMO
Thoracic spine arachnoid ossification is a relatively rare disease that affects mainly women and causes sensory, motor, and sphinctal symptoms associated with inferior limb pain. Based on three cases, the authors comment on pathogenic and surgery-related aspects of the disease. The patient in Case 1 was followed over the course of 23 years. Spinal cavitation is highlighted in Case 2, and yellow, gross, half-ring ossification is described in Case 3. Calcium deposits usually occur in the middle and lower thoracic spine where the majority of trabeculated arachnoid cells are located. Operative treatment does not interrupt the ossification process, which continues over time, causing progressive deterioration in the patient. Spinal cavitation can occur due to spinal cord tethering, stretching, and central cord edema formation, accompanied by cerebrospinal fluid blockage and pulse pressure changes. The results of surgical intervention are poor, offering short-term recovery with later deterioration. Multiple pathogenic factors are involved in this clinical syndrome including metabolic changes.