SEARCH · PubMed Health

Results for “Metabolic dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed2000

Microvascular perfusion and transport in the diabetic heart.

Diabetes is a chronic disease of metabolic dysfunction that is increasing world-wide. The hyperglycemia associated with diabetes causes significant protein alterations and an oxidative stress. In the heart, all cell types are affected by diabetes: the myocyte, the vasculature and the blood cells. Four out of five diabetics die from ischemic heart disease and stroke, suggesting that the diabetic is quite vulnerable to ischemic injury. It is important to understand the pathophysiologic challenges that occur in the diabetic heart in order to develop thoughtful treatments to limit this serious complication. This review focuses on the anatomical and functional alterations that occur in the diabetic circulation of the heart, with emphasis on the coronary microcirculation. Coronary microvascular dysfunction combined with blood cellular alterations are presented to explain the amplified oxidative stress that occurs in the diabetic heart under ischemic conditions.

Animals↗

PubMedDate not supplied

[The informative value of biochemical and cytochemical markers in laboratory animals during field tests].

Field tests (delivery of animals to differently polluted areas having) were carried out. The criterial significance of biochemical and cytochemical tests of bronchoalveolar lavage (BAL) from the animals was defined. The biochemical tests revealed significant changes in total protein, cholesterol, phospholipids, phospholipase A, histamine, serotonin, and others, which indicates metabolic dysfunction in BAL. The findings suggest that the lysosomal cell membranes are disorganized and the permeability of cell mitochondrial membranes is impaired. Thus, analyzing the findings makes it possible to identify the key links of damages and to define the true significance of environmental factors in realizing the mechanisms of pulmonary preabnormality.

Animals↗

PubMedDate not supplied

Index of lipid peroxidation and glucose utilization in the cerebrospinal fluid in patients with cerebral infarction.

Cerebral ischemia could be observed as acute metabolic crisis, when oxygen and glucose supply is compromised and synthesis of energy is insufficient. Apart from the excitotoxicity, increased production of reactive oxygen species with consequent lipid peroxidation is also included in neuronal cell damage. Furthermore, these toxic compounds could also be produced during the process of secondary inflammation of ischemic tissue. In the early stage of ischemia, as a systemic response to acute stress, there is an increase in glucose level in cerebrospinal fluid (CSF) and peripheral blood. According to the metabolic crisis and acidosis in ischemic brain tissue we investigated index of lipid peroxidation (ILP) and glucose utilization (IGU) in CSF of 53 patients of both sexes, aged 55-70 years with cerebral infarction. Control group comprised 15 patients with sudden onset of motor deficit subjected to diagnostic lumbar radiculography and suspected on discal genesis. ILP in CSF, as the indicator and sequela of neuronal cell membranes damage, was two fold increased in the acute period of cerebral infarction and maximal values (3.5 times) were noticed 24 hours after the ischemic episode compared to controls. Besides the increase in glucose concentration in peripheral blood and CSF of patients with cerebral infarction, IGU was decreased (37%) with minimal values (32%) 24 hours after the ischemia. These changes indicate that glucose is available but cells are incapable to metabolize it. We concluded that ILP and IGU in CSF of patients with cerebral infarction could be indicators of metabolic dysfunction and neuronal cell damage. Also, these results suggest the significance of polyvalent therapy including antioxidative and antiinflammatory agents in acute phase of cerebral ischemia.

Aged↗

PubMed2001

Free radicals, exercise, apoptosis, and heat shock proteins.

Free radicals are an integral part of metabolism and are formed continuously in the body. Many sources of stress heat, irradiation, hyperoxia, inflammation and any increases in metabolism including exercise, injury, and even repair processes lead to increased production of free radicals and associated reactive oxygen or nitrogen species (ROS/RNS). Evidence is accumulating that free radicals have important functions in the signal network of cells, including induction of growth and apoptosis and as killing tools of immunocompetent cells. Endogenous and nutritional antioxidant systems have to be adjusted to ensure adequate removal of radicals during stress to prevent damage to membranes, proteins, or nucleic acids. Excessive stress will induce DNA damage in the form of oxidized nucleosides, strand breaks, or DNA-protein crosslinks. Possible consequences of DNA damage are repair, apoptosis/necrosis, or defective repair leading to DNA sequence alterations and possibly to the development of cancer or, in case of mitochondrial DNA, to metabolic dysfunction. Excessive exercise will also induce DNA damage in peripheral leukocytes. The good message is that moderate stress in form of regular exercise/training may have protective effects against exercise-induced DNA damage. Up-regulation of endogenous antioxidant defense systems and complex regulation of repair systems such as heat shock proteins (HSP 70, HSP 27, HO 1) are seen in response to training and exercise. Up-regulation of antioxidants and modulation of the repair response may be mechanisms by which exercise can beneficially influence our health. Massive intervention into the redox state by pharmaceutical doses of exogenous antioxidants should be regarded with caution due to the ambiguous role of free radicals in regulation of growth, apoptosis, and cytotoxicity by immunocompetent cells.

Adaptation, Biological↗

PubMed2002

Soluble tumour necrosis factor alpha receptor 2, a serum marker of resistance to the anabolic actions of growth hormone in subjects with HIV disease.

Therapies are still being sought for the prevention of loss of body weight and lean body mass in HIV disease. The purpose of the present study was to identify a serum marker that would help in selecting patients who may be appropriate candidates for the use of anabolic agents, such as growth hormone, to restore lean body mass. This study included 26 HIV-infected patients and nine healthy controls, assessed previously for the effectiveness of 2 weeks of growth hormone administration in the stimulation of protein synthesis in skeletal muscle. Serum levels of interleukins-1beta, -6 and -10 were not useful predictors of the anabolic response to growth hormone. Serum concentrations of tumour necrosis factor alpha (TNFalpha) were significantly elevated (P<0.05) in patients with AIDS and AIDS-related weight loss, and there was a significant correlation between the serum concentration of interleukin-1 receptor antagonist and stage of disease (P=0.03). However, the serum concentration of the soluble TNFalpha receptor type 2 was most predictive of an inability of muscle protein synthesis to respond anabolically to growth hormone (r=-0.42, P=0.01). These data suggest that inflammation impacts on the responsiveness of muscle tissue to an anabolic stimulus, and that the soluble TNFalpha receptor type 2 provides a useful serum marker for metabolic dysfunction in HIV disease, which can be used to identify individuals likely to respond to growth hormone-based anabolic therapy.

Adult↗

PubMed2001

[Vitamin E: structure, metabolism, and functions].

Vitamin E is a generic term denoting eight different isomers among which alpha-tocopherol is the most important and most active. Vitamin E metabolism is closely linked to lipids during intestinal absorption, plasma secretion and transport, and tissue uptake. It is a key compound involved in many physiological processes, such as neurological and immune functions. The most common role of vitamin E is its antioxidant effect, protecting molecules and tissues against the deleterious effect of free radicals. Vitamin E also contributes to the stabilization of biological membranes. In addition, it intervenes in the regulation of several enzymes and probably has impact on gene expression. Advancing knowledge about vitamin E has been achieved with high performance liquid chromatography, making assay accessible to many laboratories, and the use of deuterated derivatives to better apprehend its metabolism. Certain issues remain unresolved concerning the molecular basis of vitamin E's mechanism of action and the exact nature of metabolic dysfunction leading to the clinical manifestations of severe vitamin E deficiency.

Humans↗

PubMed1979

[Progress in the field of parenteral feeding].

A calorie sufficient intravenous nutrition for the severely ill is possible today with practically no limitations. Carbohydrates and fats are available as energy-donators. The maximum administration rate for glucose is 0.5 g/kg/h, however, in the postoperative phase it is only 0.25 g/kg/h. The dosage limit for fructose and sorbitol is likewise 0.25 g/kg/h and only 0.125 g/kg/h for xylitol. By taking advantage of the various metabolic pathways for the individual carbohydrates, a mixed-carbohydrate solution has been developed which is utilizable in a dosage of 0.5 g/kg/h. The fat emulsions which are commercially available today consist of soy bean oil with egg lecithin or phosphatides as emulsifiers. They are well tolerated and offer several advantages in contrast to high-percentage carbohydrate solutions. In newer developments, MCT fats are added as quickly utilizable substrates. Only L-amino acids should be used today in parenteral nutrition because of their specific utilization by the organism. In addition to the administration rate (0.1 g/kg/h), the relationship between essential and non-essential amino acids is decisive for utilization, whereby the so-called E/T ratio should be as high as possible. Improved substrate utilization can be achieved through the simultaneous administration of carbohydrates, protein and fat as well as minerals and vitamins, whereby the total daily requirement can be administered within 12 hours without metabolic dysfunction.

Amino Acids↗

PubMed2002

[Use of levofloxacin in the antibiotic prophylaxis for diagnostic procedures in urology].

Chemoprophylaxis is the use of antimicrobial agents before contamination in the hope of preventing infections. The need for prophylaxis depends on the type of procedure and the risk for each individual patient. The risk for infection from urethral catheterization in a hospital setting is 5% for men and 10-20% for women, after routine cystoscopy is 4.7%, after transurethral resection of the bladder (TURB) is 39%, after transurethral resection of the prostate (TURP) is 6-43%, after transrectal biopsy of the prostate is 6.2-87%, and after shock wave lithotripsy is 5.7%. On this basis prophylactic treatment is recommended in all patients for transrectal prostate biopsy and transurethral surgery and in patients with increased risk of infection for diagnostic endoscopy of the urinary tract and SWL. Risk factors such as age, immunosuppression, metabolic dysfunction (e.g., diabetes), reduced general condition, prolonged operative time and bleeding, should be considered. Broad-spectrum cephalosporin, penicillins and fluoroquinolones are most often used. The choice of the drug also depends on its pharmacokinetic properties that should secure effective tissue levels during the procedure. Levofloxacin meets these criteria and reduces the incidence of infection after transrectal prostate biopsy and endoscopy of the urinary tract.

Aged↗

PubMed2002

Changes in mitochondrial status associated with altered Ca2+ homeostasis in aged cerebellar granule neurons in brain slices.

In the present work, we investigated the relationship between mitochondrial function and Ca2+ homeostasis in brain slices obtained from mice that aged normally. In acute preparations, the cerebellar neurons had similar values for intracellular free Ca2+ ([Ca2+]i) regardless of their age (range, 6 weeks to 24 months). However, compared with the young slices, the aged neurons (20-24 months) showed an enhanced rate of [Ca2+]i increases as a function of the time the slices were maintained in vitro. When slices were stimulated (KCl depolarization), there were significant differences in the patterns of [Ca2+]i signal displayed by the young and old cerebellar granule neurons. More importantly, the aged neurons showed a significant delay in their capacity to recover the resting [Ca2+]i. The relationship between [Ca2+]i and mitochondrial membrane potential was assessed by recording both parameters simultaneously, using fura-2 and rhodamine-123. In both young and aged neurons, the cytosolic [Ca2+]i signal was associated with a mitochondrial depolarization response. In the aged neurons, the mitochondria had a significantly longer repolarization response, and quantitative analysis showed a direct correlation between the delays in mitochondrial repolarization and [Ca2+]i recovery, indicating the causal relationship between the two parameters. Thus, the present results show that the reported changes in Ca2+ homeostasis associated with aging, which manifest principally in a decreased capacity of maintaining a stable resting [Ca2+]i or recovering the resting [Ca2+]i values after stimulation, are primarily attributable to a metabolic dysfunction in which the mitochondrial impairment plays an important role.

Aging↗

PubMed2001

[Protective effect of Panax quinquefolium 20s-proto-panaxdiolsaponins on acute myocardial infarction in dogs].

OBJECTIVE: To study the protective effects of Panax quinquefolium 20s-protopanaxdiolsaponins extracted from leaves of P. quinquefolium (PQDS) on acute myocardial infarction(AMI) in dogs. METHOD: The parameters of myocardial infart size, the serum CK and LDH activity, myocardial metabolism, free radicals and coronary circulation etc were determined by using the model of ligation of LAD in the anaesthetized open-chest dogs. RESULT: In dogs treated with PQDS(in a dosage of 10 and 20 mg.kg-1 i.v. infusion), the myocardial infarct size, the activity of serum CK, LDH and the contents of serum FFA and LPO were decreased, whereas the activity of serum SOD and GSH-Px increased markedly. At the same time, myocardial blood flow was increased and coronary vascular resistance decreased significantly. CONCLUSION: PQDS has protective effect on myocardial ischemia by modifying metabolic dysfunction of FFA, inhibiting oxygen free radical mediated peroxidation of membrane lipids, enhancing endogenous antioxidase activity and increasing myocardial blood supply.

Animals↗

PubMed2002

MR spectroscopic pulvinar sign in a case of variant Creutzfeldt-Jakob disease.

We report MR spectroscopic findings in a patient hospitalized with biopsy-proven variant Creutzfeldt-Jakob (vCJD) disease. N-acetyl aspartate was markedly decreased in the postero-medial part of the thalami (pulvinar) but was not diminished in the parieto-occipital white matter and cortical grey matter. These observations, which are in accordance with the pathological findings in this disease, suggest that MR spectroscopy, a highly sensitive method for the detection of subtle brain metabolic dysfunction, could be of interest for the diagnosis, prognosis and therapeutic follow-up of vCJD.

Adult↗

PubMed1999

Biochemical changes and gene expression following traumatic brain injury: Role of spreading depression.

The effects of spreading depression-like DC depolarizations on biochemical changes and gene expression were examined following trau-matic neocortical lesions, as induced by transcranial cold injury. The surrounding of traumatic cold lesions was characterized by increased glu-cose and lactate contents, without major disturbances of protein synthesis or energy state. A transient pH decrease by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline values by 3 h. These changes were similar in animals with spontaneous spreading depression-like DC shifts (n = 14) and those without spreading depressions (n = 7), but there was a marked difference in the gene response. In injured animals without SD, only a short-lasting response of c-fos, junB, c-jun and MKP-1 mRNAs as well as c-Fos protein was bilaterally found in the piri-form cortex, and - with ipsilateral dominance - the dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injure d animals with spreading depressions, on the contrary, a strong elevation was seen in layers II-IV and VI of the injury-remote ipsilateral cerebral cortex, which persisted over as long as 6 h. The expression of c-fos, junB and MKP-1 mRNAs was closely related to the time interval between the last spreading depression and the end of the experiments. Levels were highest shortly after transient DC shifts, and decreased thereafter mono-exponentially with half-lives of 48, 75 and 58 min for c-fos, junB and MKP-1 mRNAs, respectively. Thus, spreading depression is a prominent factor influencing the trauma-related gene response, but - in contrast to focal ischemia - it does not aggravate the metabolic dysfunction.

Journal Article↗

PubMed2003

Severe anaemia in childhood cerebral malaria is associated with profound coma.

BACKGROUND: Severe anaemia in children with cerebral malaria has been associated with respiratory distress secondary to lactic acidosis and/or hypoxia. The ensuing metabolic derangement may further depress the level of consciousness culminating in presentation with profound coma. This association has poorly been studied. OBJECTIVE: To determine the relationship between profound coma at presentation and the presence of severe anaemia in children with cerebral malaria. METHODS: This cross-sectional study involved 100 children with cerebral malaria who were consecutively recruited at admission in the Paediatric emergency unit of Mulago hospital in Uganda from July to December 2000. Clinical and laboratory evaluation was done using the hospital's guidelines for the management of severe malaria. The exposure factor of interest was severe anaemia (Hb < 5.0 g/dl) and occurrence of profound coma (Blantyre coma Scale 0) was the outcome measure. RESULTS: Severe anaemia and profound coma were seen in 20% and 9% of the children respectively. Severe anaemia was independently associated with profound coma, adjusted OR 1.34 (CI 1.17 - 1.95), p = 0. 002 and age < 3 years, adjusted OR 1.42 (CI 1.13 - 1.54), p = 0.001). Thirty percent of those with severe anaemia had deep sighing (acidotic) breathing compared to only 15% of those with haemoglobin (Hb) > 5 g/dl, OR 1.21 (CI 0.90 - 1.64), p = 0.118. There was no association between the malaria parasite density and severe anaemia. A similar proportion of those with severe anaemia regained consciousness within 24 hours compared to those with Hb > 5 g/dl (30 vs 42.5%), OR 1.56 (0.65 - 3.71), p = 0.307. CONCLUSIONS: The findings suggest that profound coma in cerebral malaria may not only result from primary malaria encephalitis but possibly also from a metabolic dysfunction due to severe anaemia.

Anemia↗

PubMedDate not supplied

[Metabolic intolerance to exercise].

Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC.

Adenosine Deaminase↗

PubMed1992

[Drusen in Bruch's membrane. Their significance for the pathogenesis and therapy of age-associated macular degeneration].

The drusen found in Bruch's membrane represent precursors for the development of age-related macular degeneration. The pathogenetic concepts are summarized: 1. As a result of aging changes in the metabolism of the pigment epithelium with age, the normal structure of Bruch's membrane is destroyed. This process is associated with lipid accumulation and the development of drusen. The lipids deposited are predominantly phospholipids or neutral lipids. 2. The clinical appearance of drusen can also vary from one person to another, but individually a significant symmetry of drusen characteristics can be seen, demonstrating that drusen are the results of specific metabolic dysfunctions rather than non-specific aging products. 3. The development of specific forms of age-related macular degeneration corresponds with different drusen. Larger, more confluent and hypofluorescent drusen are associated with the development of pigment epithelium detachments. In eyes with smaller, scattered and hyperfluorescent drusen, choroidal neovascularizations are more likely. 4. Histochemically, larger, hypofluorescent drusen contain predominantly neutral lipids. In contrast, smaller, hyperfluorescent drusen consist predominantly of phospholipids. 5. The accumulation of neutral lipids in Bruch's membrane is therefore associated with Pigment epithelium detachments. These apolar lipids may produce a hydrophobic barrier in Bruch's membrane for the water transport from the retina towards the choroid. A pigment epithelium detachment can develop. 6. The deposition of polar phospholipids predisposes to the development of choroidal neovascularization. These lipids in association with the changed structure of Bruch's membrane may induce an inflammation--like reaction, resulting in the in-growth of choroidal capillaries under the pigment epithelium. The analysis of the relationship between subclinical aging changes in Bruch's membrane and different forms of age-related macular degeneration may help to identify specific risk factors and to predict the future outcome in individual eyes. This may result in differentiated treatment concepts adapted to the specific aging changes in each person.

Adolescent↗

PubMed1977

[Parasitic calcifications: elements for diagnostic (author's transl)].

Among the radiologic calcifications, those of parasitic etiology are rather commonly found. They are heterotopic dystrophic calcifications, their late apparition in the evolution of the parasitic disease is not subordinate to any metabolic dysfunction. The authors describe the morphologic and the topographic criteria of different parasitic calcifications except the fungic ones and protozoaire. Moreover they state for each parasite some epidemiological, biological and clinical facts which can be helpful for the diagnosis.

Acanthocephala↗

PubMed1992

Efficacy of monoclonal antibody against tumor necrosis factor alpha in an endotoxemic baboon model.

Tumor necrosis factor alpha (TNF) has been described as a primary mediator of the pathophysiology associated with bacterial sepsis/endotoxemia. We tested the efficacy and possible mechanisms of protection of a monoclonal antibody against TNF (TNF Mab) in a low mortality (29%), endotoxemic baboon model. A number of parameters were monitored at days 0, 1, 2 and 5-7 after challenge with 2 mg E. coli endotoxin/kg. TNF Mab pretreatment (15 mg/kg) prevented the increase in detectable serum TNF and the early perturbations in cardiovascular function which occurred in the control group. Early metabolic dysfunction was delayed in the TNF MAb group and was attenuated thereafter. Dysfunction of the kidney, liver, and coagulation systems and the increased IL-6 levels were significantly attenuated in the TNF MAb group; neutrophil activation was not affected by TNF MAb. No deaths occurred in the TNF MAb group. These results support the hypothesis that TNF plays a central role in the pathophysiology of endotoxic shock.

Animals↗

PubMed2003

Consequences of intra-uterine growth retardation for postnatal growth, metabolism and pathophysiology.

Intra-uterine growth retardation (IUGR), caused by maternal undernutrition or placental insufficiency, is usually associated with disproportionately large reductions in the growth of some fetal organs and tissues (thymus, liver, spleen, thyroid) and impaired cellular development of other tissues (small intestine, secondary wool follicles, skeletal muscle). Growth of other tissues, most notably brain, is relatively unimpaired. In our restudy of postnatal consequences of IUGR in the offspring of prolific ewes, growth-retarded newborn lambs tended to be hypoglycaemic and showed sluggish postnatal engagement of the growth hormone (GH)-insulin-like growth factor (IGF) system. When artificially reared in an optimum environment, low birth weight lambs grew at rates similar to those of normal lambs. However, low birth weight lambs were fatter at any given weight, apparently related to their high energy intakes, especially soon after birth, had low maintenance energy requirements, and limited capacity for bone and muscle growth. These growth characteristics were accompanied by higher plasma concentrations of GH and leptin, and lower concentrations of insulin-like growth factor I (IGF-I) during the first 2 weeks of postnatal life, and higher concentrations of insulin during subsequent growth up to 20 kg body weight. Emerging evidence indicates that in sheep, as in rodents, fetal programming of postnatal cardiovascular and metabolic dysfunctions is associated with IUGR and may be mediated partly by overexposure of the fetus to cortisol. Similar postnatal responses can be elicited by maternal undernutrition or cortisol treatment in early to mid-pregnancy without changing the growth of the fetus or placenta.

Animals↗