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 217 records · Page 12Linked to original sources

PubMed1995

[Physiologic, biochemical and genetic aspects of malignant hyperthermia].

Malignant hyperthermic syndrome (MHS) is based on a metabolic dysfunction of the skeletal muscle. It is characterized by an elevation of muscle metabolism and rigidity, accompanied by an increase of arterial pCO2, lactate and potassium plasma concentration, and body temperature. In sensitive individuals, MHS can be evoked pharmacologically. To identify substances that evoke this syndrome or those useful for its therapy, MHS is modelled in pigs. The primary defect attributed to MHS is the impairment of sarcoplasmic calcium homeostasis based on a dysfunction of one of calcium ion channels. In some cases, genetic mapping has shown that MHS is related to changes in 19 chromosome (in humans). Abnormal function of the ion channel is probably not sufficient for the expression of MHS. The syndrome manifests only when several modifying factors coincide.

Animals↗

PubMed1995

[Physiologic, biochemical and genetic aspects of malignant hyperthermia].

Animals↗

PubMedDate not supplied

Intestinal mucosal enzymes in the diagnosis of gastrointestinal metabolic disease.

The small intestinal mucosa is an actively metabolizing, rapidly proliferating, absorptive epithelium with nutritional and homeostatic functions. A metabolic dysfunction of this organ might, therefore, be expected to cause not only gastrointestinal dysfunction, but also systemic symptoms. Several diseases characterized by primary or secondary gastrointestinal metabolic alterations are discussed.

Acrodermatitis↗

PubMed1991

Characterization of an endotoxemic baboon model of metabolic and organ dysfunction.

An anesthetized endotoxemic baboon model has been developed by infusing 2.0 mg E. coli endotoxin/kg i.v. over 1 hr (n = 7). Animals were monitored for 5-7 days with analyses of: cardiovascular, metabolic, and organ dysfunction; acid base, hemostatic, and hematological alterations; as well as tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels. Pathophysiologies detected at 2 hr included transient decreases in vascular resistance and blood pressure, a 157% increase in blood lactate, and a 90% decrease in circulating neutrophils. Organ dysfunction was not observed until 24 hr and, although thrombocytopenia was prevalent (-72% at 48 hr), disseminated intravascular coagulation (DIC) was not a major pathology. Hematocrit fell 21% by 24 hr and was -41% at 5-7 days. Serum TNF peaked at 90 min (7.8 +/- 0.2 ng/mL) and was undetectable after 3 hr. IL-6 also increased early, peaked at 3 hr (3872 +/- 846 U/mL) and was still detectable at 24 hr. A low mortality primate model of gram-negative sepsis has been developed that is characterized by early cardiovascular and metabolic dysfunction (2-6 hr), late organ dysfunction (24-48 hr), sub-clinical DIC, a prolonged anemia, and a 29% mortality between 48 and 72 hr.

Acid-Base Equilibrium↗

PubMed1998

Pharmacotherapy for traumatic brain injury: a review.

Traumatic brain injury in the United States is a serious health problem: it is a significant factor in approximately half of all trauma-related deaths, and, leads to persistent, long-term neurologic dysfunction in survivors. Physiological changes that accompany brain trauma such as cardiovascular alterations, hypercapnia, hypoxiaischemia, metabolic dysfunction, and alterations in the endogenous neurochemical systems are associated with poor clinical outcome. Using a variety of animal models, experimental studies have begun to elucidate these neurochemical disturbances that underlie the behavioral deficits and the pathologic outcome. Modification of the post-traumatic neurochemical milieu can promote functional recovery. While a number of currently available pharmaceutical compounds have been reported to be effective in various animal models of TBI, their utility in the clinical setting has been disappointing [119]. New hope has arisen for the treatment of TBI, based upon new research findings regarding the development of novel pharmacological therapies for brain trauma. Reduction of brain temperature can maintain relative tissue homeostasis by lowering metabolic activity. Hypothermia has been attempted in patients over the past 50 years and recent experimental evidence suggests that posttraumatic hypothermia can attenuate EAA release and free-radical production [120]. In animal models, hypothermic treatment has attenuated post-traumatic neurologic motor dysfunction [121,122], improved histopathologic damage [123,124], and reduced the extent of cytoskeletal damage [120]. In addition, the armamentarium of potentially neuroprotective compounds, which has increased rapidly in the recent years, provides promising pharmacological therapies for the treatment of TBI.

Animals↗

PubMed2006

Plasma 5-hydroxytryptamine (5-HT) in migraine during an attack-free period.

OBJECTIVE: We measured the plasma 5-HT, 5-hydroxytryptophan (5-HTP), and tryptophan levels in controls, migraine patients with aura (MWA), and migraine patients without aura (MWoA) during an attack-free period. BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of migraine. The precise relationship between 5-HT and migraine, however, remains unclear. METHODS: Blood samples in controls, MWA, and MWoA patients during an attack-free period were collected from brachial arteries and analyzed using HPLC. RESULTS: The plasma tryptophan and 5-HTP levels were not significantly different between the controls and migraine patients (either MWA or MWoA). However, the plasma 5-HT level in the MWA patients was significantly lower than that in the controls and MWoA patients. CONCLUSIONS: The present data suggest that reduced levels of 5-HT in MWA may result from either a dysfunction in the enzymes involved in serotonin biosynthesis or a dysfunction in 5-HT release or uptake from platelets and lymphocytes. These findings indicate the existence of a serotonin metabolism dysfunction in MWA patients that may differ from the state of serotonin metabolism in MWoA patients.

5-Hydroxytryptophan↗

PubMed2005

A crossover study on lipid and weight changes associated with olanzapine and risperidone.

RATIONALE: The results from case-control and retrospective studies revealed that olanzapine might be associated with more increased risks of metabolic dysfunction than risperidone. The crossover design can minimize the influence of individual variation in metabolic profiles and demographic variables, such as age, sex, concomitant medication use and personal life styles. OBJECTIVES: We design a crossover study to evaluate the metabolic effect of olanzapine and risperidone. METHODS: Fifteen schizophrenic patients were shifted from olanzapine and risperidone or from risperidone and olanzapine due to poor treatment response. The body weights, lipid profiles and fasting glucose levels were assessed before medication switch and 3 months after crossover. RESULTS: In the seven patients taking risperidone at the time of inclusion (risperidone-first group), after shifting to olanzapine, there was a significant increase in triglyceride level (p=0.048) and body weight (p=0.008). In the other eight patients (olanzapine-first group), after shift to risperidone, there was a decrease in triglyceride level (p=0.009), body weight (p=0.049) and body mass index (BMI; p=0.04). When comparing the metabolic profiles in all patients after olanzapine and after risperidone (irrespective of the order of treatment), the mean triglyceride level (p=0.001), body weight (p=0.001) and BMI (p=0.015) were significantly higher in patients receiving olanzapine than in those receiving risperidone. Furthermore, there was a small increase in total cholesterol level (p=0.091) and a small decrease in high-density lipoprotein (HDL) level (p=0.061) in olanzapine group, but the differences did not reach a significant level. There was no significant difference between olanzapine and risperidone in fasting glucose and low-density lipoprotein (LDL). CONCLUSIONS: This study confirms that elevated levels of triglyceride and body weight could be associated with the use of olanzapine as compared with risperidone. The changes in body weights and lipid profiles should be closely monitored in patients during treatment with atypical antipsychotic drugs.

Adult↗

PubMed2004

Foetal growth of kidneys, liver and spleen in intrauterine growth restriction: "programming" causing "metabolic syndrome" in adult age.

BACKGROUND/AIMS: Epidemiological studies in humans link adult disease to abnormal growth in utero. In addition to general malnutrition of the foetus, preferential blood flow to the brain and heart may furthermore deprive organs such as the liver, spleen and kidneys of oxygen and macro- and micronutrients. As a consequence, these organs may not develop normally, which predisposes the individual to the so-called metabolic syndrome (syndrome X) in later life. The effects of foetal undernutrition on the growth of some abdominal organs were investigated by comparing the volume of the kidneys, spleen and liver in small-for-gestational-age (SGA) newborn infants with that in appropriate-for-gestational-age (AGA) newborn infants. METHODS: In 25 randomly selected AGA infants and 25 SGA infants, who were subdivided into three gestational age groups (<30, 30-36 and 37-40 wk) the volumes of the liver, kidneys and spleen were determined by ultrasonography. Organ volumes were estimated using the standard ellipsoid formula (longitudinal x anteroposterior x transverse diameter x pi/6). Liver/kidney, liver/spleen and kidney/spleen volume ratios were also determined. RESULTS: The volumes of the kidneys and liver differed significantly between AGA and SGA infants in all three gestational age groups (p < 0.0018 and p < 0.029, respectively). The fact that the spleen volume differed only in the 37-40 wk group (p = 0.0002) may indicate that there is a graded relationship across the whole range of normal birthweight. The correlation between the liver volume and birthweight differed significantly between SGA and AGA infants (r = 0.56 vs 0.84, p = 0.04). On the other hand, the volume ratios between the three organs were the same in all groups (p > 0.15). CONCLUSION: In intrauterine growth retarded infants, foetal growth of the liver and kidneys is more impaired than the body as a whole. Retarded foetal development of these organs may cause metabolic dysfunction, which predisposes to the group of diseases included in the so-called metabolic syndrome or syndrome X.

Autopsy↗

PubMed2003

The effect of aldosterone on glucose metabolism.

There is an association of glucose intolerance and diabetes with primary aldosteronism, but the frequency and mechanisms are not clear. This paper reviews the possible mechanisms of impaired glucose metabolism in primary aldosteronism. Patients with primary aldosteronism can have impaired pancreatic insulin release and reduction in insulin sensitivity. These effects may be due to hypokalemia, but the evidence suggests other factors such as a direct impact of excess aldosterone on insulin action in contributing to the metabolic dysfunction. In general adrenal surgery in cases of aldosterone-producing adenoma will correct the metabolic abnormalities, but it is less sure if treatment with spironolactone in cases of idiopathic hyperplasia will correct impaired glucose tolerance.

Aldosterone↗

PubMed1990

Growth of Bacillus stearothermophilus on glycerol in chemostat culture: expression of an unusual phenotype.

Bacillus stearothermophilus grew readily on glycerol in carbon-limited chemostat culture and expressed a high carbon conversion efficiency. However, the strain of organism used (probably B. stearothermophilus var. nondiastaticus) proved particularly sensitive to glycerol, both respiration and growth being severely impeded by any surfeit of this compound. Sensitivity was found to correlate with an exceptionally high level of expression of glycerol kinase [activities of more than 80 mumol min-1 (mg protein)-1 were manifest in crude cell-free extracts], coupled with low activities of methylglyoxal synthase and of glyoxylase (enzymes of the methylglyoxal bypass). It is proposed that metabolic dysfunction results from an uncontrolled gross accumulation of glycerol phosphate (and early products of its metabolism) within the cells, coupled with depletion of the intracellular phosphate pool.

Carbon Dioxide↗

PubMed1996

Skeletal muscle metabolism as a target for drug therapy in peripheral arterial disease.

Peripheral arterial disease (PAD) is an atherosclerotic disease which modifies lower extremity hemodynamics. There is considerable evidence that skeletal muscle metabolism is altered in PAD. Several studies have demonstrated altered mitochondrial enzyme content in PAD muscle as compared with controls, and enzyme activity may not increase normally in PAD with exercise training. A variety of metabolic intermediates, including acylcarnitines, accumulate in muscle of PAD patients, suggesting incomplete oxidative metabolism. Studies employing 31P-NMR (nuclear magnetic resonance) also suggest a metabolic myopathy in PAD. Strikingly, while hemodynamics do not predict claudication-limited performance, metabolic injury as evidenced by acylcarnitine accumulation is strongly correlated with patients' functional status in PAD. Further, exercise rehabilitation improves claudication-limited performance without modifying large vessel hemodynamics. The stress placed on skeletal muscle during exercise in PAD and the observed evidence of metabolic dysfunction is similar to ischemia/reperfusion injury in cardiac muscle. Recognition of the role of cellular metabolic injury and function in PAD has formed the basis for novel therapeutic strategies in this disease.

Adenosine Triphosphate↗

PubMed1992

PET correlates of normal and impaired memory functions.

To date, positron emission tomography (PET) has been the only technology for the quantitative imaging of the changes of regional cerebral glucose (rCMRGl) or oxygen metabolism and blood flow (rCBF) associated with psychophysical stimulation and with the performance of mental tasks. So far, the majority of studies performed in healthy subjects demonstrated activation patterns involving not only certain limbic structures, most of all hippocampus, amygdala, parahippocampus, and cingulate, but also temporal, parietal, and occipital association cortex, depending on the applied paradigm. Indeed, the closest correlation between regional metabolism and memory test scores was found in mesiotemporal structures during the performance of memory tasks. Metabolic or CBF studies also seem to indicate that memorizing strategies may differ among individuals. PET was repeatedly used to investigate metabolic and/or blood flow abnormalities in patients with various amnestic syndromes. In cases with uni- or bilateral lesions of mesiotemporal structures, caused by surgery, herpes simplex encephalitis, or permanent ischemic, anoxic, or toxic damage, disturbances of metabolism and blood flow typically extended far beyond the morphological defects detected by computed tomography or magnetic resonance. In acute transient global amnesia, CBF and metabolism were decreased bilaterally in the mesiotemporal lobes, where hypometabolism persisted for some time, while higher values were observed in thalamus and some cortical areas. Diencephalic lesions causing Korsakoff's syndrome were associated with decreased rCMRGl in the hippocampal formation, upper brainstem, cingulate, and thalamus. Discrete thalamic infarcts caused amnesia and metabolic depression in the morphologically intact ipsilateral thalamus and in various projection areas of the infarcted nuclei. In ischemic forebrain lesions, amnestic deficits could be related to involvement of the anterior cingulate and of basal cholinergic nuclei. A large number of pathologies are diffusely spread out in the brain and affect partially or predominantly structures in memory processing. This holds true especially in the various dementias where memory disturbances are a consistent and often leading feature. Notably, Alzheimer's disease can be distinguished from other dementias by its characteristic pattern of metabolic dysfunction, with the most prominent changes occurring in parietotemporal and frontal association cortex whose residual metabolism is related to the severity of the disease. Therefore, activation studies using paradigms involving memory functions enhance that typical pattern. Only in the activated state is metabolism of mesiotemporal structures significantly correlated with the performance in memory tests. Other dementias also affect some of the distributed memory networks, with Huntington's disease suggesting a role of the striatum in memory processing.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

Ceramide 1-phosphate/ceramide, a switch between life and death.

Ceramide is a well-characterized sphingolipid metabolite and second messenger that participates in numerous biological processes. In addition to serving as a precursor to complex sphingolipids, ceramide is a potent signaling molecule capable of regulating vital cellular functions. Perhaps its major role in signal transduction is to induce cell cycle arrest, and promote apoptosis. In contrast, little is known about the metabolic or signaling pathways that are regulated by the phosphorylated form of ceramide. It was first demonstrated that ceramide-1-phosphate (C1P) had mitogenic properties, and more recently it has been described as potent inhibitor of apoptosis and inducer of cell survival. C1P and ceramide are antagonistic molecules that can be interconverted in cells by kinase and phosphatase activities. An appropriate balance between the levels of these two metabolites seems to be crucial for cell and tissue homeostasis. Switching this balance towards accumulation of one or the other may result in metabolic dysfunction, or disease. Therefore, the activity of the enzymes that are involved in C1P and ceramide metabolism must be efficiently coordinated to ensure normal cell functioning.

Ceramides↗

PubMed2004

Inhibition of peroxisomal functions due to oxidative imbalance induced by mistargeting of catalase to cytoplasm is restored by vitamin E treatment in skin fibroblasts from Zellweger syndrome-like patients.

Many of the peroxisomal diseases exhibit excessive oxidative stress leading to neurological alterations and dysfunction. The role of peroxisomal oxidative stress in cellular function was highlighted by the loss of metabolic functions in peroxisomes of mutant cell lines, where catalase is mistargeted to the cytoplasm, but restored to peroxisomes by genetic manipulation (Sheikh et al. [Proc. Natl. Acad. Sci. USA 95 (1998) 2961)]. We report here that two human skin fibroblast cell lines from Zellweger syndrome-like patients are defective in the import of catalase into peroxisomes, causing impairment of metabolic function of this organelle. However, by lowering the cell culturing temperature (30 degrees C) the targeting of catalase to peroxisomes was restored, and with it the metabolic functions. Furthermore, mislocalization of catalase induces an oxidative imbalance in the cells which on treatment with a natural antioxidant, alpha-tocopherol (vitamin E), resulted in reduction of the oxidative levels and restoration of metabolic function (peroxisomal beta-oxidation and levels of very long chain fatty acids and plasmalogen as well as alpha-oxidation of branched-chain fatty acids). However, restoration of peroxisomal functions was not associated with the targeting of catalase to peroxisomes. Therefore, our finding suggests that correction of mistargeted catalase to peroxisomes is a temperature sensitive event and supports the hypotheses that its location outside peroxisomes induces an oxidative imbalance that results in metabolic dysfunction. The imbalance can be reversed by treatment with vitamin E, leading to normalization of peroxisomal functions. These findings open a novel approach for therapeutic treatment of certain peroxisomal disorders where gene or hypothermic therapies are not an option.

Antioxidants↗

PubMed1998

Costello syndrome: phenotype, natural history, differential diagnosis, and possible cause.

We describe 8 patients affected with Costello syndrome including an affected sib pair and review the literature on 29 previously reported cases. We emphasize an association with advanced parental age, which is consistent with autosomal dominant inheritance with germline mosaicism. The pathogenesis appears to involve metabolic dysfunction, with growth disturbance, storage disorder appearance, acanthosis nigricans, hypertrophic cardiomyopathy, and occasional abnormalities of glucose metabolism. Although the cause is currently unknown, Costello syndrome is interesting because of a potential genetic-metabolic etiology.

Acanthosis Nigricans↗

PubMed2002

Advances in polycystic ovary syndrome treatment: metformin and ovarian diathermy.

Polycystic ovary syndrome (PCOS) affects approximately 6% of women in their reproductive years. The symptoms of the syndrome are chronic anovulation and androgen excess. Infertility due to ovulatory dysfunction is a common problem for women with PCOS. Metformin, an antihyperglycemic agent, can correct the metabolic dysfunction that occurs with PCOS, and also stimulate folliculogenesis. The drug is effective alone and in combination with clomiphene citrate. An alternative option, ovarian diathermy, also promotes ovulation through changes in the intraovarian hormonal environment. Both techniques provide promising and effective alternatives for women with PCOS who do not respond to traditional oral ovulation induction agents.

Algorithms↗

PubMed2001

Targeting ceramide metabolism--a strategy for overcoming drug resistance.

Inherent or acquired drug resistance, which frequently characterizes cancer cells, is caused by multiple mechanisms, including dysfunctional metabolism of the lipid second messenger ceramide. Ceramide, the basic structural unit of the sphingolipids, plays a role in activating cell death signals initiated by cytokines, chemotherapeutic agents, and ionizing radiation. Recent discoveries about the metabolism of ceramide suggest that this agent may have an important influence on the effectiveness of various cancer therapeutics. In particular, the cytotoxic effect of chemotherapy is decreased when generation of ceramide is impaired but is increased when the degradation of ceramide is blocked. Herein, we review the mechanisms of resistance to chemotherapeutic agents in terms of ceramide metabolism.

Animals↗

PubMed2006

Early intervention to achieve optimal outcomes in type 2 diabetes: a case presentation.

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.

Diabetes Mellitus, Type 2↗