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Biomedical subjects

Ana Navarro

Publications and source records attributed to Ana Navarro.

At least 19 recordsLinked to original sources
PubMed2007

Pesticides and impairment of mitochondrial function in relation with the parkinsonian syndrome.

The Parkinsonian syndrome induced by pesticides is associated with the impairment of mitochondrial function. Toxicants that inhibit selectively NADH-dehydrogenase activity, as rotenone or pyridaben, also show a selective inhibition of O2 uptake and respiratory control in rat brain mitochondria in the presence of NAD-dependent substrates. The IC50 of rotenone and pyridaben for complex I inhibition were in the range 1.7-2.2 microM. The determination of NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome oxidase activities in rat brain submitochondrial showed again the selective inhibition of Complex I by rotenone and pyridaben, whereas paraquat produced a non-selective inhibition affecting all the respiratory chain complexes. In rat brain mitochondria, rotenone and pyridaben markedly decreased mtNOS functional activity with NAD-dependent substrates but not when the substrate was succinate. This observation suggest than mtNOS activity is regulated by the activity of complex I. This regulation and the role of mitochondrial NO diffusion as a signal for mitochondrial biogenesis could have a role in the etiopathology of Parkinson's disease.

Animals↗
PubMed2007

Brain mitochondrial dysfunction in aging: conditions that improve survival, neurological performance and mitochondrial function.

Mice with (a) high spontaneous neurological activity, or subjected to (b) moderate exercise or (c) dietary supplemented with high doses of vitamin E from 28 weeks of age to senescence (76 wk of age), showed an increased survival and a retardation in the development of the neurological deficits associated to aging. During aging there was an increase in dysfunctional brain mitochondria, characterized by an increased content of oxidation products and by a diminished functional activity. The mitochondrial oxidative damage observed in adult (52 wk) and senescent mice (76 wk) was partially ameliorated in the groups of animals subject to the mentioned experimental conditions, and this decrease in mitochondrial oxidative damage was related to the improvement in neurological performance. In brain mitochondria, the activities of enzymes that are critical for mitochondrial function (mtNOS, NADH-dehydrogenase, and cytochrome oxidase) decreased progressively during aging and constituted aging markers. Usual clinical recommendations for aged humans, such as increased neurological activity, moderate exercise, and vitamin E supplementation, proved to be effective in increasing mice survival and neurological performances, along with a better mitochondrial function and a lower content of oxidation products.

Aging↗
PubMed2007

Role of nitric oxide on mitochondrial biogenesis during the ovarian cycle.

The mitochondrial changes in the ovary during the ovarian cycle are adapted to a cyclically increased-decreased energy demand. In the proliferative phase, the increased energy needs are sustained by the recruitment of mitochondria in active state 3, by an increased tissue O2 consumption and ATP production and by an increase in the number of mitochondria. In the phase of decreased energy needs, mitochondria-dependent apoptosis reduces tissue and mitochondrial O2 uptake. The ovary morphological changes during the cycle describe a process in which the follicles undergo a clear cycle with two sequential phases: proliferation and apoptosis. The follicular growth stimulated by FSH characterizes a tissue that shows a quick cell proliferation. During the ovarian cycle, tissue and mitochondrial O2 uptakes, mitochondrial mass, mitochondrial NO production and cytochrome oxidase activity exhibit a biphasic pattern, with marked increases in the ovary proliferative phases. Relatively low levels of NO seem to drive the cell signaling for follicle proliferation, whereas relatively high NO levels trigger mitochondria-dependent follicle apoptosis.

Animals↗
PubMed2007

Mitochondrial dysfunction in human colorectal cancer progression.

The classic association between cancer and mitochondrial dysfunction is actually considered as a role of mitochondria in cellular signalling. It is understood that mitochondria, mitochondrial oxidative damage and NO and H2O2 diffusion are involved in the progression of human colorectal cancer. Mitochondria from human colorectal tumors and adjacent non-tumor colon tissues showed a markedly increased oxidative damage with increased contents of TBARS and protein carbonyls. Mitochondrial protein carbonyls was the most sensitive indicator. Oxidative stress and damage was also observed in adjacent non-tumor cells. Mitochondrial activities, as NADH-cytochrome c reductase and cytochrome oxidase, were observed decreased in tumor and in adjacent non-tumor tissue. Cu,Zn-SOD activity decreased by 42% in tumor tissue in the advanced stage as compared with the initial stage, whereas Mn-SOD activity did not change in tumor progression. An increased mtNOS activity (46%) was observed in tumor and non-tumor tissues in the advanced stage of cancer progression. A direct linear relationship between mtNOS and oxidative damage in tumor and non-tumor tissues supports the concept that mitochondrial NO and H2O2 diffuse from tumor to adjacent non tumor tissue signaling for cell death as the classic toxohormones.

Colorectal Neoplasms↗
PubMed2007

Dietary thioproline decreases spontaneous food intake and increases survival and neurological function in mice.

Male mice on a diet supplemented with thioproline (l-thiazolidine-4-carboxylic acid), a physiological metabolite of 5-hydroxytryptamine, at 2.0 g/kg of food from 28 weeks of age and for their entire life, showed a 23-29% increased median and maximal life span. These survival increases were associated with improved neurological functions. Compared to control mice, thioproline-supplemented mice had a 20% lower integral spontaneous food intake, and 10% lower body weight at 100 weeks of age. Body weight showed a statistically significant inverse relationship with survival and neurological performances. Thioproline-supplemented mice exhibited a 58-70% decrease of the age-dependent oxidative damage in brain and liver mitochondria at 52 weeks (old mice) and 78 weeks (senescent mice) of age, respectively. The age-associated decrease of brain mitochondrial enzyme activities, NADH-dehydrogenase, cytochrome c oxidase, and mitochondrial nitric oxide synthase (mtNOS), in old and senescent mice were markedly prevented (51-74%) by thioproline. In vitro, thioproline neither exhibited direct antioxidant activity nor had any effect on the electron transfer or mtNOS functional activities of brain and liver mitochondria. It is surmised that thioproline induces an anorexic effect associated with improved survival and neurological function through a decreased oxidative damage and regulation that may involve hypothalamic appetite centers.

Age Factors↗
PubMed2006

The mitochondrial energy transduction system and the aging process.

Aged mammalian tissues show a decreased capacity to produce ATP by oxidative phosphorylation due to dysfunctional mitochondria. The mitochondrial content of rat brain and liver is not reduced in aging and the impairment of mitochondrial function is due to decreased rates of electron transfer by the selectively diminished activities of complexes I and IV. Inner membrane H(+) impermeability and F(1)-ATP synthase activity are only slightly affected by aging. Dysfunctional mitochondria in aged rodents are characterized, besides decreased electron transfer and O(2) uptake, by an increased content of oxidation products of phospholipids, proteins and DNA, a decreased membrane potential, and increased size and fragility. Free radical-mediated oxidations are determining factors of mitochondrial dysfunction and turnover, cell apoptosis, tissue function, and lifespan. Inner membrane enzyme activities, such as those of complexes I and IV and mitochondrial nitric oxide synthase, decrease upon aging and afford aging markers. The activities of these three enzymes in mice brain are linearly correlated with neurological performance, as determined by the tightrope and the T-maze tests. The same enzymatic activities correlated positively with mice survival and negatively with the mitochondrial content of lipid and protein oxidation products. Conditions that increase survival, as vitamin E dietary supplementation, caloric restriction, high spontaneous neurological activity, and moderate physical exercise, ameliorate mitochondrial dysfunction in aged brain and liver. The pleiotropic signaling of mitochondrial H(2)O(2) and nitric oxide diffusion to the cytosol seems modified in aged animals and to contribute to the decreased mitochondrial biogenesis in old animals.

Aging↗
PubMed2006

Evolving technology in bipolar perfused radiofrequency ablation: assessment of efficacy, predictability and safety in a pig liver model.

Bipolar radiofrequency (RF) ablation, especially with perfusion of saline, has been shown to increase volume over monopolar conventional methods. The aims of this study are to study whether this method is linked to too flattened thermal lesions and premature rise of impedance and to elucidate some safety concerns. Eighteen RF ablations were performed using a 1.8-mm-diameter bipolar applicator in the liver of nine healthy pigs through laparotomy with or without temporary vascular occlusion [the Pringle maneuver (PGM)]: group A (n=9), without PGM; group B (n=9), with PGM. Hypertonic saline solutions (3% and 20 %) were injected through the applicator at a rate of 400 ml/h during the procedure. The pigs were followed up and they were euthanased on the 15th day. Impedance, current, power output, energy output, temperatures, diameters of thermal lesion, volume, sphericity ratio of thermal lesion were correlated among groups. Impedance at the end of the procedure (50.00 Omega+/-28.39 and 52.88 Omega+/-26.77, for groups A and B, respectively) was very similar to the starting impedance (50 Omega). In a median of 1 (range, 0-6) time per RF ablation procedure a reduction of 30 W from the selected power supply was observed during the RF ablation procedure linked to a slight increase of impedance. Volume and short diameter of thermal lesion were 21.28 cm3+/-11.78 and 2.85 cm+/-0.87 for group A, 87.51 cm3+/-25.20 and 4.31 cm+/-0.65 for group B. Continuous thermal between both electrodes were described with a global sphericity ratio of 1.91. One major complication (thermal injury to the stomach) was encountered in a case of cross-sectional necrosis of the targeted liver and attributed to heat diffusion after the procedure. This method has been shown to determine: (1) the relative control of impedance during the procedure; (2) ovoid and relatively large thermal lesions with less dependence upon closest vessels.

Analysis of Variance↗
PubMed2006

Effects of gestational diabetes mellitus on proteins implicated in insulin signaling in human placenta.

OBJECTIVE: Placenta plays a central role in fetal nutrition. During gestational diabetes mellitus (GDM), it suffers structural and functional alterations which affect the health of both mother and fetus. In the present study we aimed to clarify if GDM modifies the amounts of leptin receptor (Ob-R) and of the main proteins implicated in insulin signal transmission (insulin receptor, insulin receptor substrate-1 and phosphatidylinositol-3-kinase subunit p85alpha) in human placenta; we also attempted to confirm the presence of estrogen receptor-alpha to determine the effect of GDM on its amount. METHODS: Placentas were recovered from 30 women with uncomplicated pregnancies and 20 women who developed GDM. Western blotting and immunocytochemistry experiments were performed to investigate the above-mentioned proteins. RESULTS: We observed that all proteins studied were increased in GDM. However, it is unknown if this is a consequence of GDM or the result of medical treatments used to mitigate the injurious effects of GDM. CONCLUSIONS: Probably, the changes we found are indicative of the protective role of the placenta prior to the injurious effects of GDM and/or an important indicator of placental aging. Some aspects related to the link between non-genomic estrogen action, the mitogenic action of insulin and the role of Ob-R in placenta from normal and GDM women need to be investigated in greater depth.

Adult↗
PubMed2006

Clinical and metabolic changes after conventional treatment of type 2 diabetic patients with chronic periodontitis.

BACKGROUND: The aim of this study was to compare the response to conventional periodontal treatment between patients with or without type 2 diabetes mellitus from a clinical and metabolic standpoint. METHODS: A prospective, parallel, comparative longitudinal clinical study was performed between type 2 diabetics and non-diabetics with moderate generalized chronic periodontitis. The study period was 6 months. Conventional periodontal scaling and root planing were performed, and the response to this treatment was compared between the groups at 3 and 6 months, measuring the plaque index, bleeding on probing, probing depth, level of clinical attachment, and gingival recession. In the diabetic patients, the clinical response was related to measurements of HbA1c and glucose in blood at 3 and 6 months. RESULTS: An improvement in all clinical variables was observed, with no statistically significant differences between the groups, with the exception of probing depth (P <0.0207). The improvement observed in blood HbA1c levels confirmed a positive metabolic response to periodontal treatment, with a lower value for this variable at each measurement time. CONCLUSIONS: Both groups of patients showed a clinical improvement after basic non-surgical periodontal treatment. The diabetic patients showed improved metabolic control (lower HbA1c) at 3 and 6 months after periodontal treatment.

Aged↗
PubMed2006

Application of Photoshop and Scion Image analysis to quantification of signals in histochemistry, immunocytochemistry and hybridocytochemistry.

OBJECTIVE: To describe a simple method to achieve the differential selection and subsequent quantification of the strength signal using only one section. STUDY DESIGN: Several methods for performing quantitative histochemistry, immunocytochemistry or hybridocytochemistry, without use of specific commercial image analysis systems, rely on pixel-counting algorithms, which do not provide information on the amount of chromogen present in the section. Other techniques use complex algorithms to calculate the cumulative signal strength using two consecutive sections. To separate the chromogen signal we used the "Color range" option of the Adobe Photoshop program, which provides a specific file for a particular chromogen selection that could be applied on similar sections. The measurement of the chromogen signal strength of the specific staining is achieved with the Scion Image software program. CONCLUSION: The method described in this paper can also be applied to simultaneous detection of different signals on the same section or different parameters (area of particles, number of particles, etc.) when the "Analyze particles" tool of the Scion program is used.

Animals↗
PubMed2005

Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice.

Male mice receiving vitamin E (5.0 g alpha-tocopherol acetate/kg of food) from 28 wk of age showed a 40% increased median life span, from 61 +/- 4 wk to 85 +/- 4 wk, and 17% increased maximal life span, whereas female mice equally supplemented exhibited only 14% increased median life span. The alpha-tocopherol content of brain and liver was 2.5-times and 7-times increased in male mice, respectively. Vitamin E-supplemented male mice showed a better performance in the tight-rope (neuromuscular function) and the T-maze (exploratory activity) tests with improvements of 9-24% at 52 wk and of 28-45% at 78 wk. The rates of electron transfer in brain mitochondria, determined as state 3 oxygen uptake and as NADH-cytochrome c reductase and cytochrome oxidase activities, were 16-25% and 35-38% diminished at 52-78 wk. These losses of mitochondrial function were ameliorated by vitamin E supplementation by 37-56% and by 60-66% at the two time points considered. The activities of mitochondrial nitric oxide synthase and Mn-SOD decreased 28-67% upon aging and these effects were partially (41-68%) prevented by vitamin E treatment. Liver mitochondrial activities showed similar effects of aging and of vitamin E supplementation, although less marked. Brain mitochondrial enzymatic activities correlated negatively with the mitochondrial content of protein and lipid oxidation products (r2 = 0.58-0.99, P < 0.01), and the rates of respiration and of complex I and IV activities correlated positively (r2 = 0.74-0.80, P < 0.01) with success in the behavioral tests and with maximal life span.

Aging↗
PubMed2005

Mitochondrial function and mitochondria-induced apoptosis in an overstimulated rat ovarian cycle.

Female rats were treated with FSH (40 IU/kg) on the first and second diestrus days (D1 and D2) and with LH (40 IU/kg) on the proestrus (P) day to synchronize and maximize ovarian changes. Follicle area increased by 50% from D1 to P, and the estrus (E) phase showed multiple corpora lutea and massive apoptosis. Increased oxygen uptakes (42-102%) were determined in ovary slices and in isolated mitochondria in active state 3 along the proliferation phase (D1-D2-P) that returned to initial values in the E phase. Mitochondrial content and the electron transfer activities of complexes I and IV were also maximal in the P phase (20-79% higher than in D1). Production of NO by mitochondrial nitric oxide synthase (mtNOS), biochemically determined, and the mtNOS functional activity in regulating state 3 oxygen uptake were also maximal at P and 79-88% higher than at D1. The moderately increased rate of NO in the proliferative phase is associated with mitochondrial biogenesis, whereas the high rate of NO generation by mtNOS at phase P appears to trigger mitochondria-dependent apoptosis. The calculated fraction of ovary mitochondria in state 3 was at a minimal value at the P phase. Mitochondrial oxidative damage, with increased thiobarbituric acid-reactive substances and protein carbonyls, indicates progressive mitochondrial dysfunction between phases P and E. The roles of mitochondria as ATP provider, as a source of NO to signal for mitochondrial proliferation and mitochondria-dependent apoptosis, and as a source of O(2)(-) and H(2)O(2) appear well adapted to serve the proliferation-apoptosis sequence of the ovarian cycle.

Animals↗
PubMed2004

Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging.

The mitochondrial mass of rat brain and liver remained unchanged on aging in young adults, old adults, and senescent animals (28, 60, and 92 wk of age); the values were 15-17 and 29-31 mg protein/g for brain and liver, respectively. The whole aging process was associated with an increased content of the oxidation products, thiobarbituric acid-reactive substances and protein carbonyls, by 61-69% in brain and 36-45% in liver, respectively. The activities of critical enzymes for mitochondrial function, mitochondrial nitric oxide synthase, Mn-superoxide dismutase, complex I, and complex IV, decreased progressively during aging with activity losses of 73, 37, 29, and 28%, respectively, in the brain and 47, 46, 30, and 24% in the liver of senescent rats compared with young adults. Brain mitochondria isolated from aged rats showed increased mitochondrial fragility, as assayed by mitochondrial marker enzyme activities in the postmitochondrial supernatant, and increased volume and water permeability, as assayed by light scattering. Liver mitochondria isolated from young and old rats did not show differences in fragility and water permeability. A subpopulation of brain mitochondria with increased size and fragility was differentiated in aging rats, whereas liver showed a homogeneous mitochondrial population.

Aging↗
PubMed2004

Differential expression of apolipoprotein d in human astroglial and oligodendroglial cells.

Apolipoprotein D (Apo D) is a secreted lipocalin in the nervous system that may be related to processes of reinnervation and regeneration. Under normal conditions, Apo D is present in the central nervous system in oligodendrocytes, astrocytes, and some scattered neurons. To elucidate the regional and cellular distribution of Apo D in normal human brain, we performed double immunohistochemistry for glial fibrillary acidic protein (GFAP) and Apo D in samples of postmortem human cerebral and cerebellar cortices. Most of the GFAP-positive cells in the gray matter had features of protoplasmic astrocytes and were mainly Apo D-positive. Apo D staining was mostly confined to the cell soma and proximal processes, whereas GFAP extended to a rich and extensive array of processes. The fibrous astrocytes in the white matter were immunoreactive for GFAP but not for Apo D. In the white matter, Apo D was mainly detected in oligodendrocytes and extracellularly in the neuropil. The results of the present study support a specific behavior for each astrocyte type. These findings suggest that Apo D expression may be cell-specific, depending on the particular tissue physiology at the time of examination.

Adult↗