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Find video protocols related to scientific articles indexed in Pubmed.
Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex vivo Under Conditions Mimicking Rest and Exercise.
J. Biol. Chem.
PUBLISHED: 11-13-2014
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The sites and rates of mitochondrial production of superoxide and H2O2 in vivo are not yet defined. At least ten different mitochondrial sites can generate these species. Each site has a different maximum capacity, e.g., the outer quinol site in complex III (site IIIQo) has very high capacity in rat skeletal muscle mitochondria whereas the flavin site in complex I (site IF) has very low capacity. The maximum capacities can greatly exceed the actual rates observed in the absence of electron transport chain inhibitors, so maximum capacities are a poor guide to actual rates. Here, we use new approaches to measure the rates at which different mitochondrial sites produce superoxide/H2O2 using isolated muscle mitochondria incubated in media mimicking the cytoplasmic substrate and effector mix of skeletal muscle during rest and exercise. We find that four or five sites dominate during rest in this ex vivo system. Remarkably, the quinol site in complex I (site IQ) and the flavin site in complex II (site IIF) each accounts for about a quarter of the total measured rate of H2O2 production. Site IF, site IIIQo and perhaps site EF in the ?-oxidation pathway account for most of the remainder. Under conditions mimicking mild and intense aerobic exercise, total production is much less and the low capacity site IF dominates. These results give novel insights into which mitochondrial sites may produce superoxide/H2O2 in vivo.
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Lateral cephalometric diagnosis of asymmetry in Angle Class II subdivision compared to Class I and II.
Dental Press J Orthod
PUBLISHED: 10-04-2014
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Lateral cephalometric radiographs are traditionally required for orthodontic treatment, yet rarely used to assess asymmetries.
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IL-17 genetic and immunophenotypic evaluation in chronic graft-versus-host disease.
Mediators Inflamm.
PUBLISHED: 07-21-2014
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Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4(+) T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.
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Sources of superoxide/H2O2 during mitochondrial proline oxidation.
Redox Biol
PUBLISHED: 07-18-2014
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p53 Inducible gene 6 (PIG6) encodes mitochondrial proline dehydrogenase (PRODH) and is up-regulated several fold upon p53 activation. Proline dehydrogenase is proposed to generate radicals that contribute to cancer cell apoptosis. However, there are at least 10 mitochondrial sites that can produce superoxide and/or H2O2, and it is unclear whether proline dehydrogenase generates these species directly, or instead drives production by other sites. Amongst six cancer cell lines, ZR75-30 human breast cancer cells had the highest basal proline dehydrogenase levels, and mitochondria isolated from ZR75-30 cells consumed oxygen and produced H2O2 with proline as sole substrate. Insects use proline oxidation to fuel flight, and mitochondria isolated from Drosophila melanogaster were even more active with proline as sole substrate than ZR75-30 mitochondria. Using mitochondria from these two models we identified the sites involved in formation of superoxide/H2O2 during proline oxidation. In mitochondria from Drosophila the main sites were respiratory complexes I and II. In mitochondria from ZR75-30 breast cancer cells the main sites were complex I and the oxoglutarate dehydrogenase complex. Even with combinations of substrates and respiratory chain inhibitors designed to minimize the contributions of other sites and maximize any superoxide/H2O2 production from proline dehydrogenase itself, there was no significant direct contribution of proline dehydrogenase to the observed H2O2 production. Thus proline oxidation by proline dehydrogenase drives superoxide/H2O2 production, but it does so mainly or exclusively by providing anaplerotic carbon for other mitochondrial dehydrogenases and not by producing superoxide/H2O2 directly.
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Relationship between non-invasive haemodynamic responses and cardiopulmonary exercise testing in patients with coronary artery disease.
Clin Physiol Funct Imaging
PUBLISHED: 05-14-2014
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Non-invasive assessment of haemodynamic function by impedance cardiography (IC) constitutes an interesting approach to monitor cardiac function in patients with coronary artery disease (CAD). However, such measurements are most often performed at rest, whereas symptoms are also possible during exertion, particularly at higher intensities. In addition, the association between IC during exertion and cardiopulmonary exercise testing (CPX) is not well understood in these patients, which was the aim of this study.
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Recovery of linear and nonlinear heart rate dynamics after coronary artery bypass grafting surgery.
Clin Physiol Funct Imaging
PUBLISHED: 03-27-2014
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Conventional coronary artery bypass grafting (C-CABG) and off-pump CABG (OPCAB) surgery may produce different patients' outcomes, including the extent of cardiac autonomic (CA) imbalance. The beneficial effects of an exercise-based inpatient programme on heart rate variability (HRV) for C-CABG patients have already been demonstrated by our group. However, there are no studies about the impact of a cardiac rehabilitation (CR) on HRV behaviour after OPCAB. The aim of this study is to compare the influence of both operative techniques on HRV pattern following CR in the postoperative (PO) period.
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Current trends in reducing cardiovascular disease risk factors from around the world: focus on cardiac rehabilitation in Brazil.
Prog Cardiovasc Dis
PUBLISHED: 03-11-2014
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Cardiovascular diseases (CVD) are among the leading causes of morbidity and mortality in Brazil. Cardiac rehabilitation (CR) is a program composed of structured exercise training, comprehensive education and counseling to positively impact functional, psychological, social, and quality of life aspects in these patients. However, the delivery of formal CR programs is limited to major metropolitan centers in Brazil and does not exist in much of the national territory, specifically in the North and Northeast regions. Barriers to the inclusion of qualified patients are lack of referral by the health professionals, as well as transportation difficulties, low income, lack of insurance coverage, and low educational level. Government efforts to implement CR programs on a broader scale, to reach a larger portion of the CVD population, are imperative. Additional research must be focused on the assessment of CR referral and adherence patterns as well as the effectiveness of different CR delivery models.
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Effects of posteroanterior thoracic mobilization on heart rate variability and pain in women with fibromyalgia.
Rehabil Res Pract
PUBLISHED: 02-21-2014
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Fibromyalgia (FM) has been associated with cardiac autonomic abnormalities and pain. Heart rate variability (HRV) is reduced in FM with autonomic tone dominated by sympathetic activity. The purpose of this study was to evaluate the effects of one session of a posteroanterior glide technique on both autonomic modulation and pain in woman with FM. This was a controlled trial with immediate followup; twenty premenopausal women were allocated into 2 groups: (i) women diagnosed with FM (n = 10) and (ii) healthy women (n = 10). Both groups received one session of Maitland mobilization grade III posteroanterior central pressure glide, at 2?Hz for 60?s at each vertebral segment. Autonomic modulation was assessed by HRV and pain by a numeric pain scale before and after the intervention. For HRV analyses, heart rate and RR intervals were recorded for 10 minutes. FM subjects demonstrated reduced HRV compared to controls. Although the mobilization technique did not significantly reduce pain, it was able to improve HRV quantified by an increase in rMSSD and SD1 indices, reflecting an improved autonomic profile through increased vagal activity. In conclusion, women with FM presented with impaired cardiac autonomic modulation. One session of Maitland spine mobilization was able to acutely improve HRV.
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The 2-oxoacid dehydrogenase complexes in mitochondria can produce superoxide/hydrogen peroxide at much higher rates than complex I.
J. Biol. Chem.
PUBLISHED: 02-10-2014
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Several flavin-dependent enzymes of the mitochondrial matrix utilize NAD(+) or NADH at about the same operating redox potential as the NADH/NAD(+) pool and comprise the NADH/NAD(+) isopotential enzyme group. Complex I (specifically the flavin, site IF) is often regarded as the major source of matrix superoxide/H2O2 production at this redox potential. However, the 2-oxoglutarate dehydrogenase (OGDH), branched-chain 2-oxoacid dehydrogenase (BCKDH), and pyruvate dehydrogenase (PDH) complexes are also capable of considerable superoxide/H2O2 production. To differentiate the superoxide/H2O2-producing capacities of these different mitochondrial sites in situ, we compared the observed rates of H2O2 production over a range of different NAD(P)H reduction levels in isolated skeletal muscle mitochondria under conditions that favored superoxide/H2O2 production from complex I, the OGDH complex, the BCKDH complex, or the PDH complex. The rates from all four complexes increased at higher NAD(P)H/NAD(P)(+) ratios, although the 2-oxoacid dehydrogenase complexes produced superoxide/H2O2 at high rates only when oxidizing their specific 2-oxoacid substrates and not in the reverse reaction from NADH. At optimal conditions for each system, superoxide/H2O2 was produced by the OGDH complex at about twice the rate from the PDH complex, four times the rate from the BCKDH complex, and eight times the rate from site IF of complex I. Depending on the substrates present, the dominant sites of superoxide/H2O2 production at the level of NADH may be the OGDH and PDH complexes, but these activities may often be misattributed to complex I.
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Production of superoxide/H2O2 by dihydroorotate dehydrogenase in rat skeletal muscle mitochondria.
Free Radic. Biol. Med.
PUBLISHED: 01-20-2014
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Dehydrogenases that use ubiquinone as an electron acceptor, including complex I of the respiratory chain, complex II, and glycerol-3-phosphate dehydrogenase, are known to be direct generators of superoxide and/or H2O2. Dihydroorotate dehydrogenase oxidizes dihydroorotate to orotate and reduces ubiquinone to ubiquinol during pyrimidine metabolism, but it is unclear whether it produces superoxide and/or H2O2 directly or does so only indirectly from other sites in the electron transport chain. Using mitochondria isolated from rat skeletal muscle we establish that dihydroorotate oxidation leads to superoxide/H2O2 production at a fairly high rate of about 300pmol H2O2·min(-1)·mg protein(-1) when oxidation of ubiquinol is prevented and complex II is uninhibited. This H2O2 production is abolished by brequinar or leflunomide, known inhibitors of dihydroorotate dehydrogenase. Eighty percent of this rate is indirect, originating from site IIF of complex II, because it can be prevented by malonate or atpenin A5, inhibitors of complex II. In the presence of inhibitors of all known sites of superoxide/H2O2 production (rotenone to inhibit sites in complex I (site IQ and, indirectly, site IF), myxothiazol to inhibit site IIIQo in complex III, and malonate plus atpenin A5 to inhibit site IIF in complex II), dihydroorotate dehydrogenase generates superoxide/H2O2, at a small but significant rate (23pmol H2O2·min(-1)·mg protein(-1)), from the ubiquinone-binding site. We conclude that dihydroorotate dehydrogenase can generate superoxide and/or H2O2 directly at low rates and is also capable of indirect production at higher rates from other sites through its ability to reduce the ubiquinone pool.
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An insight into the transcriptome of the digestive tract of the bloodsucking bug, Rhodnius prolixus.
PLoS Negl Trop Dis
PUBLISHED: 01-01-2014
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The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7-8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.
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Silencing of maternal heme-binding protein causes embryonic mitochondrial dysfunction and impairs embryogenesis in the blood sucking insect Rhodnius prolixus.
J. Biol. Chem.
PUBLISHED: 08-28-2013
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The heme molecule is the prosthetic group of many hemeproteins involved in essential physiological processes, such as electron transfer, transport of gases, signal transduction, and gene expression modulation. However, heme is a pro-oxidant molecule capable of propagating reactions leading to the generation of reactive oxygen species. The blood-feeding insect Rhodnius prolixus releases enormous amounts of heme during host blood digestion in the midgut lumen when it is exposed to a physiological oxidative challenge. Additionally, this organism produces a hemolymphatic heme-binding protein (RHBP) that transports heme to pericardial cells for detoxification and to growing oocytes for yolk granules and as a source of heme for embryo development. Here, we show that silencing of RHBP expression in female fat bodies reduced total RHBP circulating in the hemolymph, promoting oxidative damage to hemolymphatic proteins. Moreover, RHBP knockdown did not cause reduction in oviposition but led to the production of heme-depleted eggs (white eggs). A lack of RHBP did not alter oocyte fecundation. However, produced white eggs were nonviable. Embryo development cellularization and vitellin yolk protein degradation, processes that normally occur in early stages of embryogenesis, were compromised in white eggs. Total cytochrome c content, cytochrome c oxidase activity, citrate synthase activity, and oxygen consumption, parameters that indicate mitochondrial function, were significantly reduced in white eggs compared with normal dark red eggs. Our results showed that reduction of heme transport from females to growing oocytes by RHBP leads to embryonic mitochondrial dysfunction and impaired embryogenesis.
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Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats.
Neurochem. Res.
PUBLISHED: 06-26-2013
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Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of L-tyrosine. Our results demonstrated that the acute administration of L-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of L-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II.
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The determination and analysis of site-specific rates of mitochondrial reactive oxygen species production.
Meth. Enzymol.
PUBLISHED: 06-25-2013
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Mitochondrial reactive oxygen species (ROS) are widely implicated in physiological and pathological pathways. We propose that it is critical to understand the specific sites of mitochondrial ROS production and their mechanisms of action. Mitochondria possess at least eight distinct sites of ROS production in the electron transport chain and matrix compartment. In this chapter, we describe the nature of the mitochondrial ROS-producing machinery and the relative capacities of each site. We provide detailed methods for the measurement of H2O2 release and the conditions under which maximal rates from each site can be achieved in intact skeletal muscle mitochondria.
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Integrin participates in the effect of thyroxine on plasma membrane in immature rat testis.
Biochim. Biophys. Acta
PUBLISHED: 06-21-2013
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The secretory activity of Sertoli cells (SC) is dependent on ion channel functions and protein synthesis and is critical to ongoing spermatogenesis. The aim of this study was to investigate the mechanism of action associated with a non-metabolizable amino acid [14C]-MeAIB (alpha-(methyl-amino)isobutyric acid) accumulation stimulated by T4 and the role of the integrin receptor in this event, and also to clarify whether the T4 effect on MeAIB accumulation and on Ca2+ influx culminates in cell secretion.
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Association between IL1B (+3954) polymorphisms and IL-1? levels in blood and saliva, together with acute graft-versus-host disease.
J. Interferon Cytokine Res.
PUBLISHED: 05-09-2013
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Graft-versus-host disease (GVHD) is associated with morbidity and mortality in the recipients of allogeneic hematopoietic stem cell transplants (allo-HSCTs). Interleukin-1? (IL-1?) is a potent inflammatory mediator involved in different inflammatory conditions. Therefore, we aimed to investigate the association of IL1B gene polymorphism in recipients and donors in cases in which acute GVHD (aGVHD) has been reported and the impact of this gene polymorphism on the level of cytokines in the blood and saliva. Fifty-eight consecutive allo-HSCT recipients and their donors were prospectively studied. Saliva and/or blood samples were obtained from the recipients and donors to identify the IL1B gene polymorphism, and cytokine levels were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allo-HSCT (day+100), for a total of 16 weeks or until death. aGVHD occurred in 27 individuals evaluated. A significant association was identified between the IL1B polymorphism in the donor and aGVHD development in the corresponding recipients.?However, no significant association was detected between the IL1B polymorphism in recipients and the development of aGVHD. In the recipients who were diagnosed with aGVHD, the level of IL-1? in the saliva and blood were increased. In the saliva, IL-1? levels increased progressively from the time before the diagnosis of aGVHD until weeks after the diagnosis, whereas in the blood, IL-1? peak levels could be observed within the time allotted for diagnosis, followed by a decrease in the levels. In addition, we observed a significant association between the IL1B genotype of the recipient (CC) and high IL-1? levels in the saliva at week 13. In conclusion, IL-1? could be considered a useful predictor of aGVHD development.
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Is applying the same exercise-based inpatient program to normal and reduced left ventricular function patients the best strategy after coronary surgery? A focus on autonomic cardiac response.
Disabil Rehabil
PUBLISHED: 05-07-2013
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Abstract Purpose: To assess whether the same exercise-based inpatient program applied to patients with normal and reduced left ventricular function (LVF) evokes a similar cardiac autonomic response after coronary artery bypass graft (CABG). Method: Forty-four patients post-CABG, subgrouped according to normal LVF [LVFN: n?=?23; left ventricular ejection fraction (LVEF)???55%] and reduced LVF (LVFR: n?=?21; LVEF 35-54%), were included. All initiated the exercise protocol on post-operative day 1 (PO1), following a whole progressive program until discharge. Cardiac autonomic response was assessed by the indices of heart rate variability (HRV) at rest and during exercise (extremity range of motion and ambulation). Results: During ambulation, lower values of HRV indices were found in the LVFR group compared with the LVFN group [standard deviation of all RR (STDRR; 6.1?±?2.7 versus 8.9?±?4.7?ms), baseline width of the RR histogram (TINN; 30.6?±?14.8 versus 45.8?±?24.9?ms), SD2 (14.8?±?8.0 versus 21.3?±?9.0?ms), Shannon entropy (3.6?±?0.5 versus 3.9?±?0.4) and correlation dimension (0.08?±?0.2 versus 0.2?±?0.2)]. Also, when comparing the ambulation to rest change, lower values were observed in the LVFR group for linear (STDRR, TINN, RR TRI, rMSSD) and non-linear (SD2 and correlation dimension) HRV indices (p?
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The quality of life of disease-free Brazilian breast cancer survivors.
Rev Esc Enferm USP
PUBLISHED: 03-22-2013
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The objective of this study was to compare the quality of life of women who survived breast cancer and women who have not had the disease, and to identify associated factors. It is cross-sectional study in which the comparison group includes survivors of breast cancer aged between 40 and 69 years. One hundred and fifty-four women were included, 70 with breast cancer and 84 without the disease. The SF-36 was used to evaluate quality of life. The chi-square test and multivariate linear models were used to compare the groups. The estimated mean physical and mental components were significantly better for the group who survived the disease (51.10 and 52.25, respectively) compared to the group without cancer (47.26 and 47.93, respectively). The study indicates that survivors of breast cancer had a better quality of life compared to women without the disease.
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Comparing conventional and supercritical extraction of (-)-mammea A/BB and the antioxidant activity of Calophyllum brasiliense extracts.
Molecules
PUBLISHED: 03-05-2013
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Calophyllum brasiliense is a rich source of bioactive coumarins, xanthones and biflavonoids. The aim of the study was to compare the phenol contents and the antioxidant activity of C. brasiliense extracts obtained by conventional and supercritical fluid extraction (SFE) methods, as well as the quantification of crude extracts and (-)-mammea A/BB yields. Dichloromethane and hexane were used as solvents for the conventional extractions and SFE was developed using supercritical CO?; the kinetic curves were modeled using a second-order empirical model. The dichloromethane extract presented the best total yield, although it showed the lowest content of (-)-mammea A/BB. The concentration of the coumarin was considerably higher in extracts obtained by the supercritical fluid method and a higher antioxidant activity was assigned to extracts obtained by this technique. Concerning the total phenolic contents, both the dichloro-methane and the supercritical extractions produced satisfactory amounts. The SFE method proved to be more promising than conventional methods.
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Identification of anaerobic threshold by analysis of heart rate variability during discontinuous dynamic and resistance exercise protocols in healthy older men.
Clin Physiol Funct Imaging
PUBLISHED: 02-08-2013
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The purposes of this study were to determine anaerobic threshold (AT) during discontinuous dynamic and resistive exercise protocols by analysing of heart rate variability (HRV) and blood lactate (BL) in healthy elderly subjects and compare the cardiovascular, metabolic and autonomic variables obtained from these two forms of exercise. Fourteen elderly (70 ± 4 years) apparently healthy males underwent the following tests: (i) incremental ramp test on cycle ergometer, (ii) one repetition maximum (1RM) leg press at 45°, (iii) a discontinuous exercise test on a cycle ergometer (DET-C) protocol and (iv) a resistance exercise leg press (DET-L) protocol. Heart rate, blood pressure and BL were obtained during each increment of exercise intensity. No significant differences (P>0·05) were found between methods of AT determination (BL and HRV) nor the relative intensity corresponding to AT (30% of maximum intensity) between the types of exercise (DET-C and DET-L). Furthermore, no significant differences (P>0·05) were found between the DET-C and DET-L in relation to HRV, however, the DET-L provided higher values of systolic blood pressure and BL (P<0·05) from the intensity corresponding to AT. We conclude that HRV was effective in determination of AT, and the parasympathetic modulation responses obtained during dynamic and resistive exercise protocols were similar when compared at the same relative intensity. However, DET-L resulted in higher values of blood pressure and BL at workloads beyond AT.
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Salivary tests associated with elderly peoples oral health.
Gerodontology
PUBLISHED: 02-05-2013
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The saliva constitutes essential condition for the individuals health.
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Rapid responses to reverse T? hormone in immature rat sertoli cells: calcium uptake and exocytosis mediated by integrin.
PLoS ONE
PUBLISHED: 01-01-2013
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There is increasing experimental evidence of the nongenomic action of thyroid hormones mediated by receptors located in the plasma membrane or inside cells. The aim of this work was to characterize the reverse T? (rT?) action on calcium uptake and its involvement in immature rat Sertoli cell secretion. The results presented herein show that very low concentrations of rT? are able to increase calcium uptake after 1 min of exposure. The implication of T-type voltage-dependent calcium channels and chloride channels in the effect of rT? was evidenced using flunarizine and 9-anthracene, respectively. Also, the rT?-induced calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of integrin-ligand interactions). Therefore, our findings suggest that calcium uptake stimulated by rT? may be mediated by integrin ?v??. In addition, it was demonstrated that calcium uptake stimulated by rT? is PKC and ERK-dependent. Furthermore, the outcomes indicate that rT? also stimulates cellular secretion since the cells manifested a loss of fluorescence after 4 min incubation, indicating an exocytic quinacrine release that seems to be mediated by the integrin receptor. These findings indicate that rT? modulates the calcium entry and cellular secretion, which might play a role in the regulation of a plethora of intracellular processes involved in male reproductive physiology.
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1?,25-Dihydroxyvitamin D(3) signaling pathways on calcium uptake in 30-day-old rat Sertoli cells.
Biochemistry
PUBLISHED: 11-04-2011
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1?,25-Dihydroxyvitamin D(3) (1,25D(3)) is the active metabolite of vitamin D(3) and the major calcium regulatory hormone in tissues. The aim of this work was to investigate the mechanism of action of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells from 30-day-old rats. Results showed that 10(-9) and 10(-12) M 1,25D(3) increased the rate of (45)Ca(2+) uptake 5 and 15 min after hormone exposure and that 1?,25(OH)(2) lumisterol(3) (JN) produced a similar effect suggesting that 1,25D(3) action occurs via a putative membrane receptor. The involvement of voltage-dependent calcium channels (VDCC) in 1,25D(3) action was evidenced by using nifedipine, while the use of Bapta-AM demonstrated that intracellular calcium was not implicated. Moreover, the incubation with ouabain and digoxin increased the rate of (45)Ca(2+) uptake, indicating that the effect of 1,25D(3) may also result from Na(+)/K(+)-ATPase inhibition. In addition, we demonstrated that the mechanism underlying the hormone action involved extracellular signal-regulated kinase (ERK) and protein kinase C (PKC) activation in a phospholipase C-independent way. Furthermore, a local elevation of the level of cAMP, as demonstrated by incubating cells with dibutyryl cAMP or a phosphodiesterase inhibitor, produced an effect similar to that of 1,25D(3), and the inhibition of protein kinase A (PKA) nullified the hormone action. In conclusion, the stimulatory effect of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells occurs via VDCC, as well as PKA, PKC, and ERK activation. These protein kinases seem to act by inhibiting Na(+)/K(+)-ATPase or directly phosphorylating calcium channels. The Na(+)/K(+)-ATPase inhibition may result in Na(+)/Ca(2+) exchanger activation in reverse mode and consequently induce the uptake of calcium into the cells.
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A comparative assessment of mitochondrial function in epimastigotes and bloodstream trypomastigotes of Trypanosoma cruzi.
J. Bioenerg. Biomembr.
PUBLISHED: 08-09-2011
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Trypanosoma cruzi is a hemoflagellate protozoan that causes Chagas disease. The life cycle of T. cruzi is complex and involves different evolutive forms that have to encounter different environmental conditions provided by the host. Herein, we performed a functional assessment of mitochondrial metabolism in the following two distinct evolutive forms of T. cruzi: the insect stage epimastigote and the freshly isolated bloodstream trypomastigote. We observed that in comparison to epimastigotes, bloodstream trypomastigotes facilitate the entry of electrons into the electron transport chain by increasing complex II-III activity. Interestingly, cytochrome c oxidase (CCO) activity and the expression of CCO subunit IV were reduced in bloodstream forms, creating an "electron bottleneck" that favored an increase in electron leakage and H(2)O(2) formation. We propose that the oxidative preconditioning provided by this mechanism confers protection to bloodstream trypomastigotes against the host immune system. In this scenario, mitochondrial remodeling during the T. cruzi life cycle may represent a key metabolic adaptation for parasite survival in different hosts.
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Left-ventricular function and autonomic cardiac adaptations after short-term inpatient cardiac rehabilitation: a prospective clinical trial.
J Rehabil Med
PUBLISHED: 07-07-2011
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Cardiac rehabilitation is associated with cardiac autonomic and physiological benefits. However, it is unclear whether baseline left ventricular function (LVF) impacts on training-induced cardiac autonomic adaptations. The aim of this study was to assess the cardiac autonomic adaptations in patients with varying left ventricular function profiles undergoing coronary artery bypass grafting and cardiac rehabilitation.
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Children with Cushings syndrome: Primary Pigmented Nodular Adrenocortical Disease should always be suspected.
Pituitary
PUBLISHED: 07-02-2011
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Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare form of bilateral adrenocortical hyperplasia that is inherited in an autosomal dominant manner and leads to ACTH-independent Cushings syndrome (CS). PPNAD may be isolated or associated with Carney Complex (CNC). For the diagnosis of PPNAD and CNC, in addition to the hormonal and imaging tests, searching for PRKAR1A mutations may be recommended. The aims of the present study are to discuss the clinical and molecular findings of two Brazilian patients with ACTH-independent CS due to PPNAD and to show the diagnostic challenge CS represents in childhood. Description of two patients with CS and the many sequential steps for the diagnosis of PPNAD is provided. Sequencing analysis of all coding exons of PRKAR1A in the blood, frozen adrenal nodules (patients 1 and 2) and testicular tumor (patient 1) is performed. After several clinical and laboratory drawbacks that misled the diagnostic investigation in both patients, the diagnosis of PPNAD was finally established and confirmed through pathology and molecular studies. In patient 1, sequencing of PRKAR1A gene revealed a novel heterozygous 10-bp deletion in exon 3, present in his blood, adrenal gland and testicular tumor. The etiologic diagnosis of endogenous CS in children is a challenge that requires expertise and a multidisciplinary collaboration for its prompt and correct management. Although rare, PPNAD should always be considered among the possible etiologies of CS, due to the high prevalence of this disease in this age group.
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Effect of 1?,25-dihydroxyvitamin D3 in plasma membrane targets in immature rat testis: ionic channels and gamma-glutamyl transpeptidase activity.
Arch. Biochem. Biophys.
PUBLISHED: 06-18-2011
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1?,25-Dihydroxyvitamin D(3) (1,25D(3)) is critical for the maintenance of normal reproduction since reduced fertility is observed in vitamin D-deficient male rats. The aim of this study was to investigate the effect of 1,25D(3) in 30-day-old rat testicular plasma membrane targets (calcium uptake and gamma-glutamyl transpeptidase (GGTP) activity), as well as to highlight the role of protein kinases in the mechanism of action of 1,25D(3). The results demonstrated that 1,25D(3) induced a fast increase in calcium uptake in rat testis through a nongenomic mechanism of action. This effect was dependent on PKA, PKC and MEK. Moreover, ionic channels, such as ATP- and Ca(2+)-dependent K(+) channels and Ca(2+)-dependent Cl(-) channels, are involved in the mechanism of action. The use of BAPTA-AM showed that [Ca(2+)](i) was also implicated, and the incubation with digoxin produced an increase in (45)Ca(2+) uptake indicating that the effect of 1,25D(3) may also result from Na(+)/K(+)-ATPase inhibition. In addition, 1,25D(3) was able to increase the GGTP activity. Considered together, our results indicate a PKA/PKC/MEK-dependent 1,25D(3) pathway as well as ionic involvement leading to (45)Ca(2+) uptake in immature rat testis. These findings demonstrate that 1,25D(3) stimulates calcium uptake and increases GGTP activity which may be involved in male reproductive functions.
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Scrotal hematoma as a sign of adrenal hemorrhage in newborns.
Sao Paulo Med J
PUBLISHED: 05-24-2011
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Bluish discoloration and swelling of the scrotum in newborns can arise from a number of diseases, including torsion of the testes, orchitis, scrotal or testicular edema, hydrocele, inguinal hernia, meconium peritonitis, hematocele, testicular tumor and traumatic hematoma. Forty-two cases of scrotal abnormalities as signs of neonatal adrenal hemorrhage were found in the literature.
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[Relationship between lead levels in colostrum, dietary intake, and socioeconomic characteristics of puerperal women in Goiânia, Brazil].
Rev. Panam. Salud Publica
PUBLISHED: 05-24-2011
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To estimate the levels of lead in human colostrum and investigate whether they are correlated with dietary intake and socioeconomic factors in puerperal women.
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Neuropathology and behavioral impairments after three types of global ischemia surgery in Meriones unguiculatus: evidence in motor cortex, hippocampal CA1 region and the neostriatum.
J. Neurol. Sci.
PUBLISHED: 05-20-2011
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The effects of three types of global ischemia by occlusion of carotid artery on motor and exploratory behaviors of Gerbils were evaluated by the Activity Cage and Rota rod tests. Animals were divided based on two surgical criteria: unilateral (UNI) or bilateral (BIL) carotid occlusion, with (REP) or without (OCL) reperfusion; and their behavior was evaluated on the fourth (4) or sixth (6) day. There was reduction of cell number in striatum, motor cortex M1 area, and hippocampal CA1 area in all groups in comparison to control animals. For M1 area and striatum, the largest reduction was observed in UNI6, UNI4, and BIL4 groups. Neuronal loss was also observed in CA1 area of BIL4 rodents. There was a decrease in crossings and rearings in all groups in activity cage test, compared to control. Reperfusion, unilateral and bilateral occlusion groups showed decrease in crossings. Only the BIL4 showed a decrease of rearing. In the Rota rod test, except the UNIOCL6, the groups showed a decrease in the balance in comparison to control. Both groups with REP4 showed a major decrease in balance. These findings suggest that both unilateral and bilateral carotid occlusions with reperfusion produce impairments of motor and exploratory behavior.
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Effects of age and gender on upper airway, lower airway and upper lip growth.
Braz Oral Res
PUBLISHED: 03-18-2011
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The aim of the present retrospective study was to evaluate the influence of age and gender on upper and lower airway width and upper lip length. In this study, 390 lateral cephalograms were divided into 13 age groups (ranging from 6 to 18 years) and were analyzed. The intergroup differences were analyzed using a MANOVA (Multivariate Analysis of the Variance), and the intragroup differences were analyzed using an ANOVA (Analysis of the Variance) and Tukeys test. The results of the present study indicated that although the airway width and the upper lip length increased with age, the lower airway width exhibited variable growth between the ages of six and eighteen years. The airway width was significantly greater in females than males, whereas the upper airway width was similar between these two genders. The lip length was significantly shorter in females than males. The lower airway width and upper lip length were significantly different between males and females, whereas the upper airway width was similar for the genders. The upper airway width and upper lip exhibited incremental growth between the ages of six and eighteen years. The upper lip closely followed the growth pattern of the upper airway width; the growth plateaued between the ages of 6 and 9 years, increased from 9 to 16 years and plateaued from 16 to 18 years.
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Mental Health Policy in Brazil: federal expenditure evolution between 2001 and 2009.
Rev Saude Publica
PUBLISHED: 02-23-2011
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To analyze the evolution of estimates of federal spending in Brazils Mental Health Program since the promulgation of the national mental health law.
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Blood meal-derived heme decreases ROS levels in the midgut of Aedes aegypti and allows proliferation of intestinal microbiota.
PLoS Pathog.
PUBLISHED: 02-16-2011
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The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS) generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF) mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox) reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.
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Oral cGVHD screening tests in the diagnosis of systemic chronic graft-versus-host disease.
Clin Oral Investig
PUBLISHED: 02-16-2011
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To determine the diagnostic properties of oral manifestations and histological features of graft-versus-host disease (GVHD) screening tests in the diagnosis of systemic chronic graft-versus-host disease (cGVHD). Sixty patients having undergone allogeneic haematopoietic stem cell transplantation were selected. The patients were submitted to a clinical oral examination to assess symptoms and clinical changes in the oral mucosa. Histopathologic analysis of the lower lip oral mucosa (LLOM) and salivary glands (SG) was also performed. Systemic cGVHD was used for a comparison to oral cGVHD. The accuracy of oral cGVHD tests was low for all methods (58.4% and 52.6% for white lesions and white/red lesions, respectively, in the clinical analysis; 50.4% for the presence of oral pain; and 66.8% and 55.1% for LLOM and SG histopathologic tests, respectively). However, the presence of oral pain had good diagnostic properties [specificity: 100.0, 95% confidence interval (CI): 88.0-100.0; positive predictive value (PPV): 100.0, 95% CI: 94.4-100.0; and negative predictive value (NPV): 72.0, 95% CI: 57.3-83.3]. Moreover, SG alterations revealed by the histopathological analysis also exhibited good diagnostic properties (sensitivity: 98.6, 95% CI: 81.5-99.8; PPV: 71.1, 95% CI: 62.1-79.7; NPV: 85.9 95% CI: 32.9-99.4). The clinical severity of oral lesions and histophatological changes in the LLOM did not exhibit adequate diagnostic properties, whereas both oral pain and SG histopathological analysis exhibited adequate properties for the diagnosis of systemic cGVHD. Histological changes in lip oral mucosa and salivary glands together with a clinical manifestation of the disease in the oral mucosa can be useful to determining the systemic cGVHD.
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Heme-induced ROS in Trypanosoma cruzi activates CaMKII-like that triggers epimastigote proliferation. One helpful effect of ROS.
PLoS ONE
PUBLISHED: 02-03-2011
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Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bugs midgut. The parasite Trypanosoma cruzi, the agent of Chagas disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS) formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time- and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE) adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism.
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Energy metabolism affects susceptibility of Anopheles gambiae mosquitoes to Plasmodium infection.
Insect Biochem. Mol. Biol.
PUBLISHED: 01-26-2011
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Previous studies showed that Anopheles gambiae L3-5 females, which are refractory (R) to Plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (S) G3 females. Our studies revealed that R females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. Furthermore, when state-3 respiration was reduced in S females by silencing expression of the adenine nucleotide translocator (ANT), hydrogen peroxide generation was higher and the mRNA levels of lactate dehydrogenase increased in the midgut, while the prevalence and intensity of Plasmodium berghei infection were significantly reduced. We conclude that there are broad metabolic differences between R and S An. gambiae mosquitoes that influence their susceptibility to Plasmodium infection.
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Imatinib-associated hyperpigmentation of the palate in post-HSCT patient.
J Craniomaxillofac Surg
PUBLISHED: 01-06-2011
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Pigmentation of the oral mucosa can indicate a wide range of lesions or conditions. Some drugs are associated with pigmented lesions of oral cavity. Imatinib mesylate (Gleevec(®)) is a protein inhibitor used in the management of several hematological malignancies associated with dermatological side effects, like hyperpigmentation. We report the case of a 38-year-old male post-HSCT patient who had been using imatinib mesylate for over 5 years and presented with blue pigmentation on the hard palate, the left side of the nose and both ear lobes. The differential diagnosis of hyperpigmented lesions in the oral mucosa is also presented.
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Heart rate autonomic responses during deep breathing and walking in hospitalised patients with chronic heart failure.
Disabil Rehabil
PUBLISHED: 08-23-2010
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To evaluate the acute effect of physiotherapy (deep breathing exercises and walking) on heart rate variability in patients hospitalised with chronic heart failure (CHF).
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Adjuncts to physical training of patients with severe COPD: oxygen or noninvasive ventilation?
Respir Care
PUBLISHED: 07-01-2010
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Previous studies have shown positive effects from noninvasive ventilation (NIV) or supplemental oxygen on exercise capacity in patients with COPD. However, the best adjunct for promoting physiologic adaptations to physical training in patients with severe COPD remains to be investigated.
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Peripheral calcifying odontogenic cyst: a case report and review of the literature.
Head Neck Pathol
PUBLISHED: 06-30-2010
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The peripheral calcifying odontogenic cyst (PCOC) accounts for less than 25% of the cases of calcifying odontogenic cysts and most commonly appears as a nodule on the gingiva. This paper aims to present both a case report of a PCOC located in the left vestibular maxilla as well as a review of the English-language literature. An 11-year-old female patient presented a swelling in the vestibular region of teeth 12 and 13. Periapical and panoramic radiographs demonstrated irregular calcification. Surgical excision was performed. Microscopic examination showed an odontogenic cystic lesion lined by ameloblastoma-like epithelium, containing numerous ghost cells. Areas of calcification associated with ghost cells could also be observed. The patient was diagnosed with PCOC. The patient has been disease-free for 36 months. The review of the cases of PCOC showed 44 well-defined cases. The mean age was of 49.4 years at the time of diagnosis. The reported cases appeared as a painless swelling, with a slight predilection for females, and were more frequently located in the anterior region of the maxilla or mandible. Surgical excision is the treatment of choice, and recurrence is rare.
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[Cadmium in human milk: concentration and relation with the lifestyle of women in the puerperium period].
Rev Bras Ginecol Obstet
PUBLISHED: 06-07-2010
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To relate the cadmium concentration of colostrum with the lifestyle of women in the puerperium period.
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Short-term supervised inpatient physiotherapy exercise protocol improves cardiac autonomic function after coronary artery bypass graft surgery--a randomised controlled trial.
Disabil Rehabil
PUBLISHED: 02-17-2010
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Coronary artery bypass grafting (CABG) is accompanied by severe impairment of cardiac autonomous regulation (CAR). This study aimed to determine whether a short-term physiotherapy exercise protocol post-CABG, during inpatient cardiac rehabilitation (CR), might improve CAR.
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Investigation of functional IL-10 gene polymorphism and IL-10 levels in acute graft-versus-host disease.
J. Clin. Immunol.
PUBLISHED: 02-01-2010
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Graft-versus-host disease (GVHD) represents a major complication in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Although studies have been conducted concerning the investigation of cytokine polymorphisms in the development of acute GVHD (aGVHD), the contribution of recipients and donors as regards cytokine levels has not yet been thoroughly assessed.
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Acute application of bilevel positive airway pressure influences the cardiac autonomic nervous system.
Clinics (Sao Paulo)
PUBLISHED: 05-29-2009
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Noninvasive positive pressure has been used to treat several diseases. However, the physiological response of the cardiac autonomic system during bilevel positive airway pressure (Bilevel) remains unclear.
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Blood-feeding induces reversible functional changes in flight muscle mitochondria of Aedes aegypti mosquito.
PLoS ONE
PUBLISHED: 04-27-2009
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Hematophagy poses a challenge to blood-feeding organisms since products of blood digestion can exert cellular deleterious effects. Mitochondria perform multiple roles in cell biology acting as the site of aerobic energy-transducing pathways, and also an important source of reactive oxygen species (ROS), modulating redox metabolism. Therefore, regulation of mitochondrial function should be relevant for hematophagous arthropods. Here, we investigated the effects of blood-feeding on flight muscle (FM) mitochondria from the mosquito Aedes aegypti, a vector of dengue and yellow fever.
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The effects on Trypanosoma cruzi of novel synthetic naphthoquinones are mediated by mitochondrial dysfunction.
Free Radic. Biol. Med.
PUBLISHED: 03-24-2009
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Despite ongoing efforts, the current treatment for Chagas disease is still unsatisfactory, mainly because of the severe side effects and variable efficacy of the available nitroheterocycles. Our group has been assaying natural quinones isolated from Brazilian flora, and their derivatives, as alternative chemotherapeutic agents against Trypanosoma cruzi. From C-allyl lawsone three naphthofuranquinones were synthesized, which were active against trypomastigotes and epimastigotes. Here, we further investigated the activity and the mechanisms of action of these quinones. They exhibited powerful effects on intracellular amastigotes, presenting low toxicity to the host cells. Ultrastructural analyses of treated epimastigotes and trypomastigotes indicated a potent effect of the three naphthofuranquinones on the parasite mitochondrion, which appeared drastically swollen and with a washed-out matrix profile. Fluorescence-activated cell sorting analysis of rhodamine 123-stained T. cruzi showed that the three naphthofuranquinones caused a potent dose-dependent collapse of the mitochondrial membrane potential, especially in the epimastigote form. Naphthofuranquinones also decreased specifically mitochondrial complex I-III activity in both epimastigotes and trypomastigotes, parallel to a reduction in succinate-induced oxygen consumption. Mitochondrial hydrogen peroxide formation was also increased in epimastigotes after treatment with the naphthofuranquinones. Our results indicate that the trypanocidal action of the naphthofuranquinones is associated with mitochondrial dysfunction, leading to increased reactive oxygen species generation and parasite death.
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Association between polymorphisms in interleukin-17A and -17F genes and chronic periodontal disease.
Mediators Inflamm.
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Interleukin-17 (IL-17) is a cytokine that induces neutrophil recruitment and the release of inflammatory mediators in several inflammatory conditions; nevertheless, the involvement of IL-17 gene polymorphisms in chronic periodontitis (CP) has not been addressed yet. Our aim was to evaluate the association between periodontal status and the polymorphisms IL-17A G197A and IL-17F C7488T in subjects with CP along with their impact on levels of inflammatory mediators.
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Characteristics of women with breast cancer seen at reference services in the North of Minas Gerais.
Rev Bras Epidemiol
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To describe the main characteristics, including stage of disease and local treatment of patients admitted to two reference services for the treatment of breast cancer in the North of Minas Gerais.
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Mitochondrial reactive oxygen species modulate mosquito susceptibility to Plasmodium infection.
PLoS ONE
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Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism.
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1?,25-dihydroxyvitamin D(3) mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats.
Biochim. Biophys. Acta
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The involvement of calcium-mediated signaling pathways in the mechanism of action of 1?,25-dihydroxyvitamin D(3) (1,25D) is currently demonstrated. In this study we found that 1,25D induces nongenomic effects mediated by membrane vitamin D receptor (VDRm) by modulating intermediate filament (IF) phosphorylation and calcium uptake through L-type voltage-dependent calcium channels (L-VDCC) in cerebral cortex of 10 day-old rats. Results showed that the mechanism of action of 1,25D involves intra- and extracellular calcium levels, as well as the modulation of chloride and potassium channels. The effects of L-VDCCs on membrane voltage occur over a broad potential range and could involve depolarizing or hyperpolarizing coupling modes, supporting a cross-talk among Ca(2+) uptake and potassium and chloride channels. Also, the Na(+)/K(+)-ATPase inactivation by ouabain mimicked the 1,25D action on (45)Ca(2+) uptake. The Na(+)/K(+)-ATPase inhibition observed herein might lead to intracellular Na(+) accumulation with subsequent L-VDCC opening and consequently increased (45)Ca(2+) (calcium, isotope of mass 45) uptake. Moreover, the 1,25D effect is dependent on the activation of the following protein kinases: cAMP-dependent protein kinase (PKA), Ca(2+)/calmodulin-dependent protein kinase (PKCaMII), phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase p38 (p38(MAPK)). The modulation of calcium entry into neural cells by the 1,25D we are highlighting, might take a role in the regulation of a plethora of intracellular processes. Considering that vitamin D deficiency can lead to brain illness, 1,25D may be a possible candidate to be used, at least as an adjuvant, in the pharmacological therapy of neuropathological conditions.
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Energetic payoff of tool use for capuchin monkeys in the caatinga: variation by season and habitat type.
Am. J. Primatol.
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In this paper, we analyze predictions from the energetic bottleneck and opportunity models to explain the use of stones to crack open encased fruit by capuchins in dry environments. The energetic bottleneck model argues that tool use derives from the need to crack open hard-encased fruits which are key resources during periods of food scarcity. The opportunity model argues that tool use by capuchins derives from simultaneous access to stones and encased fruits. The study was conducted in the Caatinga biome, northeastern Brazil, at two areas where capuchin monkeys (Sapajus libidinosus and Sapajus spp.) regularly use stones to crack open encased fruit of Syagrus cearensis and Manihot dichotoma. Energetic gains were inferred based on the number of tool-use sites used and the mass of encased fruit consumed per month, and compared across seasons and areas occupied by the two groups. For the drier habitat, a significant increase in frequency of tool use (N(dry) = 329 vs. N(wet) = 59) and in the mean monthly mass of fruits consumed in the dry season (mean(dry) = 193g vs. mean(wet) = 13.5 g) offered support for the energetic bottleneck model. However, our inference of low energetic payoffs for tool using individuals (in the drier caatinga habitat from 13 to 193 cal·ind(-1) ·month(-1) and in the wetter caatinga habitat from 805 to 1150 cal·ind(-1) ·month(-1) ) offer support for the opportunity model. Finally, our analyses indicate that consumption of six S. cearensis fruits would equal the daily requirements of capuchins for ?-carotene, and the consumption of 1.22 g·day(-1) of M. dichotoma encased fruit or 1.0 g·day(-1) of S. cearensis can supply capuchins daily requirement of vitamin C. So, specific nutritional requirements may play a role in explaining the continuous consumption of encased fruit and customary use of stones to crack open encased fruit.
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