Search results for "ENERGETICS"

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment

2009

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem …

Altered Mitochondrial Function and Oxidative Stress in Leukocytes of Anorexia Nervosa Patients

2014

ContextAnorexia nervosa is a common illness among adolescents and is characterised by oxidative stress.ObjectiveThe effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated.Design and settingA multi-centre, cross-sectional case-control study was performed.PatientsOur study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women.Main outcome measuresAnthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumpt…

11,12-EET Stimulates the Association of BK Channel α and β1 Subunits in Mitochondria to Induce Pulmonary Vasoconstriction

2012

In the systemic circulation, 11,12-epoxyeicosatrienoic acid (11,12-EET) elicits nitric oxide (NO)- and prostacyclin-independent vascular relaxation, partially through the activation of large conductance Ca(2+)-activated potassium (BK) channels. However, in the lung 11,12-EET contributes to hypoxia-induced pulmonary vasoconstriction. Since pulmonary artery smooth muscle cells also express BK channels, we assessed the consequences of BKβ(1) subunit deletion on pulmonary responsiveness to 11,12-EET as well as to acute hypoxia. In buffer-perfused mouse lungs, hypoxia increased pulmonary artery pressure and this was significantly enhanced in the presence of NO synthase (NOS) and cyclooxygenase (…

Blood Flow and Tissue Oxygenation of Human Tumors: An Update

1992

It is generally accepted that tumor microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status (factors which are usually closely linked and which define the so-called cellular microenvironment) can markedly influence the therapeutic response of malignant tumors. Tumor blood flow is the major determinant for intra-tumor pharmacokinetics and (through modulation of the cellular microenvironment) of pharmacody-namics. The oxygen supply greatly determines the radiosensitivity of the tumors to be treated. The oxygen enhancement ratio, i.e., the ratio of doses with and without oxygen to produce the same biological effect is 2.7 to 3.0. O2 partial…

OXYGENATION AND BIOENERGETIC STATUS OF HUMAN TUMORS

1991

Oxygenation and Bioenergetic Status of Murine Fibrosarcomas

1992

The heterogeneity of cellular response to therapy is a major problem in non-surgical cancer therapy. This heterogeneity is influenced by both the genetic variability between different tumor cells and by epigenetic, physiological factors, such as the local metabolic milieu. A restriction of tumor microcirculation concomitant with regional hypoxia, nutrient depletion, accumulation of lactate, and an intensified tumor acidosis becomes evident during growth of many solid tumors1. These critical factors can greatly influence the efficiency of various non-surgical tumor therapies.

The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS

2021

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. It is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and paralysis. ALS is incurable and has a bleak prognosis, with median survival of 3–5 years after the initial symptomatology. In ALS, motor neurons gradually degenerate and die. Many features of mitochondrial dysfunction are manifested in neurodegenerative diseases, including ALS. Mitochondria have shown to be an early target in ALS pathophysiology and contribute to disease progression. Disruption of their axonal transport, excessive generation of reactive oxygen species, disruptio…

New evidence for the multiplicity of ubiquinone- and inhibitor-binding sites in the mitochondrial complex I.

2000

Determination of the number of ubiquinone- and inhibitor-binding sites in the mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a controversial question with a direct implication for elaborating a suitable model to explain the bioenergetic mechanism of this complicated enzyme. We have used combinations of both selective inhibitors and common ubiquinone-like substrates to demonstrate the multiplicity of the reaction centers in the complex I in contrast with competition studies that have suggested the existence of a unique binding site for ubiquinone. Our results provide new evidence for the existence of at least two freely exchangeable ubiquinone-binding sites with different specif…

Stable bioenergetic status despite substantial changes in blood flow and tissue oxygenation in a rat tumour.

1994

Experiments on s.c. rat tumours (DS sarcoma) were performed to determine whether chronic or acute changes in tumour perfusion necessarily lead to changes in tissue oxygenation and bioenergetic status since, as a rule, blood flow is thought to be the ultimate determinant of the tumour bioenergetic status. Based on this study, there is clear experimental evidence that growth-related or acute (following i.v. administration of tumour necrosis factor alpha) decreases in tumour blood flow are accompanied by parallel alterations in tissue oxygenation. In contrast, tumour energy status remains stable as long as flow values do not fall below 0.4-0.5 ml g-1 min-1, and provided that glucose as the mai…

Microregional distributions of glucose, lactate, ATP and tissue pH in experimental tumours upon local hyperthermia and/or hyperglycaemia

1993

Microregional distributions of glucose, lactate and ATP concentrations as well as tissue pH values were determined in subcutaneous rat tumours during normothermia and normoglycaemia, and upon local hyperthermia (HT) and/or hyperglycaemia (HG). Experiments were performed in order to investigate whether, and to what extent, these adjuvant therapeutic measures applied alone or in combination can modify the bioenergetic and metabolic status, parameters that are known to markedly influence the therapeutic response of tumours to heat. Local HT was performed in a saline bath (44 degrees C/2 h) and HG was induced by i.v. infusion of glucose for 2.5 h (blood glucose levels during heating: 35-40 mM).…