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PubMed2004

Serum concentrations of adiponectin and leptin in patients with thyroid dysfunctions.

Thyroid dysfunction is associated with metabolic changes that affect mass and adipocyte function, as well as lipid and carbohydrate metabolism. Adipose tissue performs complex metabolic and endocrine functions. Leptin and adiponectin are two of the most important adipocytokines, both involved in the regulation of intermediate metabolism. The aim of this study was to evaluate the relationships between thyroid status and circulating levels of the two adipose tissue hormones. We studied 15 patients with hyperthyroidism, 15 patients with hypothyroidism and 15 euthyroid subjects, all matched by sex, age and body mass index (BMI). Serum concentrations of free thyroxine, free tri-iodothyronine, thyrotropin, leptin and adiponectin and anthropometric parameters (weight, height, BMI) were assessed. No significant difference was found among the 3 groups, as assessed by Student's t-test, both for adiponectin and leptin. We conclude that metabolic changes associated with thyroid dysfunction are not related to variations in serum levels of adiponectin or leptin.

Adiponectin↗
PubMed1984

Cadmium and the kidney.

The paper is a review of certain aspects of importance of cadmium and the kidney regarding the assessment of risks and understanding of mechanisms of action. The review discusses the following topics: history and etiology of cadmium-induced kidney dysfunction and related disorders; cadmium metabolism, metallothionein and kidney dysfunction; cadmium in urine as indicator of body burden, exposure and kidney dysfunction; cadmium levels in kidney and liver as indicators of kidney dysfunction; characteristics of early kidney dysfunction; the critical concentration concept; critical concentrations of cadmium in kidney cortex; and prognosis.

Animals↗
PubMed2000

Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS.

OBJECTIVE: To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS. BACKGROUND: MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation. METHODS: Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects. RESULTS: Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP. CONCLUSION: Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.

Adult↗
PubMed2005

Endothelial dysfunction, cellular adhesion molecules and the metabolic syndrome.

Over the last two decades, it has become evident that the endothelium is more than an inert, single-cell lining covering the internal surface of blood vessels. Normally, the endothelium actively decreases vascular tone, maintains vascular permeability within narrow bounds, inhibits platelet adhesion and aggregation, limits activation of the coagulation system, and stimulates fibrinolysis. Endothelium dysfunction can be considered present when its functions, either in the basal state or after stimulation, are altered in a way that is inappropriate to the preservation of organ function. Endothelial dysfunction has been associated to many cardiovascular risk factors including diabetes, hypertension and hypercholesterolemia. In addition, endothelial dysfunction may play a crucial role in the development and progression of atherosclerosis. This review will give a brief overview of the different methods to assess endothelial function, and then will focus on the current knowledge on soluble cellular adhesion molecules in relation to the metabolic syndrome and type 2 diabetes.

Animals↗
PubMed1995

Beneficial effects of enteral fat administration on liver dysfunction, liver lipid accumulation, and protein metabolism in septic rats.

The purpose of this study was to examine the effect of different amounts of fat in enteral diets on liver function, liver lipid accumulation, and protein metabolism in septic rats. Sepsis was induced in Wistar rats by cecal ligation and puncture. The rats were divided into four groups and were fed enterally 0% (FO, n = 7), 10% (F10, n = 7), 20% (F20, n = 8), or 30% (F30, n = 9) of total calories as fat. The liquid diet consisted of medium-chain and long-chain triglyceride mixtures as the fat sources, casein oligopeptide, and dextrin (100 kcal/100 ml). Intraduodenum feeding was ended on the 6th day. Serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities, indices of liver dysfunction, were highest in the FO group, and triglycerides accumulated in the livers of that group, possibly because of the large proportion of carbohydrate in the diet. Value of nitrogen balance was highest in the F 10 group, and serum total protein and albumin concentration were higher in the F10 and F20 groups than in the FO and F30 groups. The liver protein content in the F10 and F20 groups was higher than in the FO and F30 groups. Serum triglyceride in the F30 group was about 2 times higher than in the F10 and F20 groups. These results indicate that enteral fat administration in septic rats as 30% of total calories reduced liver dysfunction and liver triglyceride accumulation, but might have been excessive for optimal protein metabolism. Therefore, the preferable amount may range from 10% to 20% of total calories.

Alanine Transaminase↗
PubMed2003

Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction.

OBJECTIVES: We sought to assess myocardial perfusion and metabolism in patients with peculiar transient asynergy, which consisted of basal normokinesia and apical akinesia of the left ventricle (LV) at the same time. BACKGROUND: This asynergy has been widely called "tako-tsubo-like LV dysfunction" in Japan, but little is known about its pathophysiology. METHODS: We performed rest tallium-201 ((201)Tl) and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid ((123)I-BMIPP) dual-isotope myocardial single-photon emission computed tomography (SPECT) in 14 patients with tako-tsubo-like LV dysfunction. The LV was divided into 17 segments, and each segment was graded with scores between normal uptake (0) and defect (4). We also measured the Thrombolysis in Myocardial Infarction trial (TIMI) frame count in 28 patients and 20 control subjects. RESULTS: Early SPECT (5 +/- 3 days) revealed that the total defect score value with BMIPP was significantly higher than reduced uptake with (201)Tl (p < 0.01). Reduced uptake of BMIPP was observed in parallel with an apical akinetic region and usually involved uptake of (201)Tl. This discrepancy improved gradually during the follow-up period (29 +/- 6 days) (p = 0.36). Compared with control subjects, patients had a TIMI frame count that was significantly higher in all coronary arteries immediately after onset. This higher TIMI frame count decreased but was sustained even after resolution of tako-tsubo-like LV dysfunction. CONCLUSIONS: Our data suggest that myocardial fatty acid metabolism is more severely impaired than myocardial perfusion, in parallel with an apical akinetic region during the early phase, and that impaired multivessel coronary microcirculation is involved, at least in part, in tako-tsubo-like LV dysfunction.

Aged↗
PubMed2002

Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine.

Mitochondria are not only the principal source of high energy intermediates, but play an important role in intracellular calcium buffering, are main producers of reactive oxygen species, and are the source of pro- and antiapoptotic key factors. Moreover, the mitochondria are of a ubiquitous nature and the respiratory chain has a dual genetic basis, i.e. the mitochondrial and the nuclear DNAs. Thus mitochondrial impairment could provide an explanation for the tremendous heterogeneity of clinical and pathological manifestations in schizophrenia. This article reviews several independent lines of evidence that suggest an involvement of mitochondrial dysfunction in schizophrenia. Among them are altered cerebral energy metabolism, mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system and altered mitochondrial related gene expression. In addition, the interaction between dopamine, a predominant etiological factor in schizophrenia, and mitochondrial respiration is considered as a possible mechanism underlying the hyper- and hypo-activity cycling in schizophrenia. Understanding the role of mitochondria in schizophrenia may encourage novel treatment approaches, the identification of candidate genes and new insights into the pathophysiology and etiology of the disorder.

Animals↗
PubMed1999

Accumulation of glycolipids in mutant Chinese hamster ovary cells (Z65) with defective peroxisomal assembly and comparison of the metabolic rate of glycosphingolipids between Z65 cells and wild-type CHO-K1 cells.

The influence of peroxisomal dysfunction on glycosphingolipid metabolism was investigated using mutant Chinese hamster ovary (CHO) cells (Z65) with defective assembly of the peroxisomal membranes. In accordance with previous observations, the concentration of very long chain fatty acid (C24:0) was shown to be higher in Z65 cells than in control cells. We then compared the composition of glycolipids in Z65 cells with that in CHO-K1 cells, which are wild-type Chinese hamster ovary cells with intact peroxisomes, and found significantly increased concentrations of ceramide monohexoside (CMH) and ganglioside GM3 in Z65 cells. However, there were no differences in the concentrations of glycerophospholipids, triglycerides, free fatty acids and cholesterol between Z65 and CHO-K1 cells. Further, to investigate the metabolic rate of the major lipids, Z65 and CHO-K1 cells were pulse-labeled with [3-14C]serine. [3-14C]Serine was incorporated into phosphatidylserine, phosphatidylethanolamine and sphingomyelin more quickly in CHO-K1 than in Z65 cells. However, after 48 h, the radioactivity incorporated into those lipids, including CMH, was greater in Z65 cells than in CHO-K1 cells. Thus, the altered metabolism of glycosphingolipids, probably due to peroxisomal dysfunction, was thought to be responsible for the change in glycosphingolipid composition in Z65 cells.

Animals↗
PubMed1994

Cadmium-induced sexual dysfunction does not involve increased hepatic metabolism of testosterone nor increased circulating levels of corticosterone.

Sexually experienced male rats were injected IP with 0, 0.3, 1.5, 3.0, or 6.0 mg/kg cadmium chloride. The highest dose was fatal within 48 h of injection. A dose-related deficit in erectile function was observed in ex copula tests 48 h after injection. Copulatory dysfunction was evident in mating tests 72 h after injection. Hepatic mixed function oxidase activity after 0.3 mg/kg injections was not different from controls, but was diminished by 50% in rats treated with 3.0 mg/kg. The higher cadmium doses (1.5 and 3.0 mg/kg) were associated with equivalent and marked reductions in circulating testosterone levels, and lesser decrements in circulating corticosterone levels. The rats treated with 1.5 or 3.0 mg/kg cadmium chloride lost weight (32 +/- 12 and 39 +/- 9 g, respectively). Relative decapsulated adrenal gland weights were markedly increased in rats treated with 3.0 mg/kg. These data indicate that exposure to cadmium is associated with alterations in sexual, hepatic, and adrenal function, with erectile dysfunction occurring at the lowest dose. The effects on copulatory behavior are especially striking because it requires some weeks for copulatory behavior to wane following castration.

Adrenal Glands↗
PubMed2005

Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction.

Diabetic cardiomyopathy is characterized by excessive utilization of fatty acid substrate, diminished glucose transport, and mitochondrial dysfunction. However, the chemical mechanisms linking altered substrate utilization to mitochondrial dysfunction are unknown. Herein, we use shotgun lipidomics and multidimensional mass spectrometry to identify dramatic decreases in the critical mitochondrial inner membrane lipid, cardiolipin, in diabetic murine myocardium (from 7.2 +/- 0.3 nmol/mg of protein in control hearts to 3.1 +/- 0.1 nmol/mg of protein in diabetic myocardium; p < 0.001, n = 7). Moreover, the direct metabolic precursor of cardiolipin, phosphatidylglycerol, was also substantially depleted (2.5 +/- 0.2 nmol/mg of protein in control hearts vs 1.3 +/- 0.1 nmol/mg of protein in diabetic myocardium; p < 0.001, n = 7). Similarly, glycerol 3-phosphate, necessary for the penultimate step in phosphatidylglycerol production, decreased by 58% in diabetic myocardium (from 4.9 +/- 0.9 to 2.2 +/- 0.3 nmol/mg of protein; n = 4). Since Barth's syndrome (a disorder of cardiolipin metabolism) induces mitochondrial dysfunction and cardiomyopathy, and since decreases in cardiolipin content precipitate mitochondrial dysfunction, these results provide a unifying hypothesis linking altered substrate utilization and metabolic flux in diabetic myocardium with altered lipid metabolism, cardiolipin depletion, mitochondrial dysfunction, and resultant hemodynamic compromise.

Animals↗
PubMed2001

Inter-relationships between renal metabolism (both in physiology and renal dysfunction) and the liver.

Recently, evaluation of organ-specific glucose release showed that renal glucose release is of the same order of magnitude as splanchnic glucose release during the postabsorptive period. Moreover, renal glucose release appeared to be more sensitive to hormone action than did hepatic glucose release, and appeared to have a pre-eminent role during the adaptation to various physiological and pathological conditions. The kidney is now recognized as playing a key role in interorgan glucose metabolism, and particularly in the Cori cycle and glutamine-glucose cycle. During chronic renal failure the suppression of renal glucose release, together with impaired hormone action, decreased glycogen storage and abnormal liver gluconeogenesis, are responsible for an increased risk for hypoglycaemia.

Adaptation, Physiological↗
PubMed1991

Detection of hereditary metabolic disorders involving amino acids and organic acids.

Inherited disorders in the metabolism of amino acids and organic acids may cause neurological dysfunction and acute metabolic crises. For many of these disorders, early diagnosis and early treatment can greatly improve the outcome. A general description of the clinical manifestations and a discussion of selected techniques and approaches for the laboratory diagnosis are reviewed.

Amino Acids↗
PubMed2002

Abnormal carbohydrate metabolism during pregnancy : association with endothelial dysfunction.

OBJECTIVE: To evaluate whether abnormal endothelial function, a common finding in premenopausal women with type 2 diabetes, is present in early states of diabetes during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Brachial artery flow-mediated dilatation (FMD) (endothelium-dependent) and nitrate-induced dilatation (NID) (endothelium-independent) were measured in 23 pregnant subjects with carbohydrate abnormalities (10 IGT, 13 GDM) and in 15 pregnant control subjects during the third trimester of gestation. High-resolution vascular ultrasonography was used to perform these investigations. A fasting lipid panel was obtained, and glucose and insulin values in response to a 100-g oral glucose load were also measured. RESULTS: FMD was significantly reduced in both groups of women with abnormal carbohydrate metabolism compared with control subjects (7.6 +/- 1.1% in the IGT group and 4.1 +/- 0.9% in the GDM group vs. 10.9 +/- 1.1% in control subjects, P < 0.04 and P < 0.0001, respectively). Significant difference in FMD was also observed between IGT and GDM groups (P < 0.04). NID was comparable in the three groups. Among all subjects, FMD showed a strong independent negative correlation with glycemic area (r=-0.60, P < 0.0001). CONCLUSIONS: Endothelial dysfunction, an early marker of macrovascular disease, is present in pregnancies complicated by IGT and GDM. This alteration, which seems to be directly related to glycemic levels, could explain, at least in part, the increased risk for concurrent hypertensive disorders during pregnancy in these women.

Adult↗
PubMed1981

Influence of early phases of paralysis on microcirculation of rat skeletal muscle.

By combining tissue pO2 measurements with morphological visualization and counting of perfused capillaries, early microvascular changes were investigated in paralysis of skeletal muscle of the rat. The models included experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), 6-aminonicotinamide intoxication, and peripheral denervation. The results showed that in all models tissue oxygenation was either normal or elevated. In most cases this was accompanied by a reduced perfusion of the capillary bed, supporting the hypothesis of a dysfunction in oxidative metabolism. The effects of paralysis on capillary perfusion were more marked in red than in white muscles, except in spastic paresis. Flaccid paralysis had more deleterious effects on muscle microcirculation than spastic paralysis. Our data suggest that: (1) microvascular changes occur very early after the onset of paralysis and (2) later developing changes in the skeletal muscle such as atrophy cannot be ascribed to a lack of oxygen supply but rather, at least in part, to a dysfunction in oxidative metabolism.

6-Aminonicotinamide↗
PubMed1990

A psychometric evaluation of adult patients with type 1 (insulin-dependent) diabetes mellitus: prevalence of psychological dysfunction and relationship to demographic variables, metabolic control and complications.

The relationship between psychosocial traits and glycaemic control and complications was examined in 130 adults (83 men, 47 women) with insulin-dependent diabetes mellitus. Abnormal depression ratings were observed in more women (19.1%) than men (12.0%), p less than 0.01, whilst obsessive symptoms were recorded more frequently in men (41.0 v 21.3%, p less than 0.01). Abnormal anxiety ratings were present in roughly 8-13% of men and women, although a notably low feeling of insecurity rating was observed more frequently in men (56.5%) than in women (38.3% of cases), p less than 0.05. Psychological scores were related to age, employment status and social class, but not to duration of diabetes or glycaemic control. The anxiety, depression and obsessive ratings correlated with one another (rs range 0.24-0.62, all p less than 0.001). Higher anxiety and depression ratings or overt psychological dysfunction was recorded in patients with neuropathic symptoms and signs, impotence, macrovascular disease or proliferative retinopathy. It is concluded that the presence of diabetic complications and adverse social circumstances are more relevant to psychological status than glycaemic control.

Adolescent↗
PubMed1989

Leukocyte endogenous mediator fails to alter protein dynamics in a model of liver dysfunction.

This study examines the effect of a purified leukocyte-derived endogenous mediator (LEM) on protein metabolism during liver dysfunction and after sham surgery and the role of a nonsteroidal, antiinflammatory drug (indomethacin sodium trihydrate) in modifying this response. Febrile response, protein kinetics, urinary end products of protein metabolism, and plasma acute phase protein levels were studied in rats given a pyrogenic dose of LEM or saline solution, and these same indicators were studied after the administration of the same dose of LEM plus 2 mg/kg indomethacin 3 weeks after a portacaval shunt (PCS) or sham operation. In both surgical groups given LEM, a maximum of 1.1 degrees C fever was observed. LEM increased protein turnover and urinary excretion of nitrogen and urea in sham-operated rats but not in the PCS animals. Administration of indomethacin decreased the plasma oxidation of L[1-14C]leucine and prevented the increased excretion of total nitrogen and urea in sham-operated animals treated with LEM. PCS animals showed a constant excretion of nitrogen and urea independent of treatment. alpha 1-Acid glycoprotein levels increased significantly in sham-operated animals treated with LEM but not in the PCS group until indomethacin was added. The coadministration of LEM and indomethacin in shams also enhanced the levels of alpha 2-macroglobulin and alpha 1-acid glycoprotein over values found with LEM alone. These findings confirm the catabolic effect of LEM in normal animals and identify the essential role of the liver in the acute phase response. The data also suggest that indomethacin may modify the acute phase response by reducing plasma amino acid oxidation as well as enhancing the levels of some specific acute phase proteins.

Acute-Phase Proteins↗
PubMed1989

Memory impairment in patients with progressive supranuclear palsy.

Verbal memory was compared in 12 patients with progressive supranuclear palsy and 12 healthy control subjects matched for age, sex, and education. Learning, consolidation, and retrieval were significantly impaired in patients with progressive supranuclear palsy. Information scanning, which requires the use of short-term memory processes, remained intact. Duration of symptoms and degree of motor dysfunction correlated with intrusions during learning. No relation between central dopamine metabolism and memory dysfunction could be established.

Aged↗