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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the role of odd and even short-chain fatty acid substrates on aerobic and glycolytic metabolism in well-aerated primary cultures of rabbit renal proximal tubule cells (RPTC). Increasing oxygen delivery to primary cultures of RPTC by shaking the dishes (SHAKE) reduced total lactate levels and lactate dehydrogenase (LDH) activity and reduced net glucose consumption compared to RPTC cultured under standard conditions (STILL). The addition of butyrate, valerate, heptanoate, or octanoate to SHAKE RPTC produced variable effects on glycolytic metabolism. Although butyrate and heptanoate further reduced total lactate levels and net glucose consumption during short-term culture (< 24 h), no fatty acid tested further reduced total lactate levels, net glucose consumption, or LDH activity during long-term culture (7 days). During the first 12 h of culture, maintenance of aerobic metabolism in SHAKE RPTC was dependent on medium supplementation with fatty acid substrates (2 mM). However, by 24 h, SHAKE RPTC did not require fatty acid substrates to maintain levels of aerobic metabolism equivalent to freshly isolated proximal tubules and greater than STILL RPTC. This suggests that SHAKE RPTC undergo adaptive changes between 12 and 24 h of culture, which give RPTC the ability to utilize other substrates for mitochondrial oxidation, therefore allowing greater expression of mitochondrial oxidative potential in SHAKE RPTC than in STILL RPTC.
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PMID:The role of short chain fatty acid substrates in aerobic and glycolytic metabolism in primary cultures of renal proximal tubule cells. 837 17

Simple cold storage of livers for transplantation activates glycolysis due to lack of oxygen. Energy derived from glycolysis may be critical for cell survival and liver cell death may occur once glycolysis is inhibited in the liver due to accumulation of end products or lack of substrates (glycogen). The relationship between cell death (lactate dehydrogenase, LDH release), anaerobic glycolysis (lactate production), and glycogen content of liver tissue was studied during cold incubation of liver slices in UW solution. Rat livers slices from male Sprague Dawley rats were incubated at 4 degrees C in UW solution, with continuous gentle shaking, under conditions of chemical hypoxia (KCN, 5 mM). The rate of lactate production, LDH release-ATP and glycogen content were measured spectrophotometrically and by HPLC. Lactate increased nearly linearly for the first 48 h of incubation; total lactate which had accumulated after 48 h was 33.9 +/- 0.81 mumol/g and at 96 h nearly the same, 31.3 +/- 1.2 mumol/g. Glycolysis stopped, apparently, because of the depletion of liver slice glycogen which was initially 228.8 +/- 1.7 mumol/g wet wt. It decreased to 34.7 +/- 2.7 mumol/g at 48 h and to 18.7 +/- 1.1 mumol/g at 72 h and remained at this level for the next 24 h. An increased leakage of LDH occurred once glycogen metabolism (and accumulation) ceased. LDH release could be stimulated after only a few hours of cold incubation of liver tissue slices by adding glycolysis inhibitor (iodoacetic acid) to the medium. After 24 h. LDH release was 24.4 +/- 1.8% and increased to 52.8 +/- 5.2% (P < 0.05, Student's t-text) with iodoacetic acid. Adding a glycolytic substrate (fructose, 10 mM) to the medium maintained lactate production for 96 h. The stimulation of glycolysis by fructose also reduced cell death: LDH release was significantly lower at 72- and 96-h incubation (P < 0.001, two-way ANOVA). The ATP content was significantly higher with fructose (P < 0.001). Adding glucose (20 mM) and fructose (10 mM) in combination resulted in prolonged cell survival, significantly delayed glycogen depletion and significantly higher ATP content at 48 and 72 h (two-way ANOVA). Livers from rats who had fasted for 24 h demonstrated the same LDH release at 48 h when incubated with glucose (20 mM) and fructose (10 mM). In conclusion, LDH leakage from hypoxic cold-stored liver slices is related to anaerobic glycolysis. Anaerobic glycolysis appears to continue slowly under hypothermia and provides sufficient energy for maintenance of cell viability. A stimulation of glycolysis in the cold is possible by fructose and results in prolonged cell survival under hypothermic conditions. Glycogen depletion can be slowed down by combining glucose and fructose.
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PMID:[Liver metabolism during cold ischemic incubation in UW solution in the rat model]. 949 7

The primary objective of this study was to characterize an in-vitro model of the human placenta using morphological, biochemical and physiological parameters. Placental villi were obtained from normal first trimester and term pregnancies. The villi were incubated with Dulbecco's modified Eagle's medium: Ham's F12 nutrient mixture in a shaking water bath at 37 degrees C for up to 310 min. The viability was determined by the production of beta human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH) and the incorporation of [3H]thymidine, [3H]L-leucine and L-[U14C]arginine, while ultrastructure was assessed by transmission electron microscopy. In the first and third trimester group, the release into the medium of the intracellular enzyme LDH remained unaltered throughout the experiment. By contrast, beta-HCG concentrations increased linearly and concentrations were higher in the first trimester than term villi (354.5 +/- 37.8 versus 107 +/- 8.1 IU/g villi protein; P < 0.001). Electron microscopy confirmed preservation of tissue viability for up to 4 h of incubation. The incorporation of thymidine (12.2 +/- 2.9 versus 5.2 +/- 0.5 nmol/g villi protein; P < 0.05), leucine (9.4 +/- 2.1 versus 1.9 +/- 0.4 nmol/g villi protein; P < 0.02) and arginine (17 +/- 4.4 versus 4.2 +/- 0.5 nmol/g villi protein; P < 0.05) were markedly higher in early than in term placenta. Furthermore, placental uptake of L-leucine by the first (9.4 +/- 2.1 versus 17 + 4.4 mol/g villi protein; P < 0.001) and third trimester placental villi (1.9 +/- 0.4 versus 4.2 + 0.5 mol/g villi protein; P < 0.001) was less than that of L-arginine. This study describes a simple technique using placental explants to determine relative rates of uptake of substrate amino acids throughout gestation.
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PMID:Characterization of human placental explants: morphological, biochemical and physiological studies using first and third trimester placenta. 1010 6

The authors submit the case-history of a 29-year-old man, followed up on account of liver steatosis with a toxic-nutritional etiology who developed, after previous increased physical exertion and alcohol abuse, fever associated with major muscular weakness. Gradually he developed an amental delirious state which was evaluated as suspect delirium tremens. Fever of 40-41 degrees C continued, the patient developed muscular rigidity, tremor and hypotension. After intubation during which succinylcholine was administered, the patient's condition deteriorated further with a rise of temperature and muscular rigidity. The patient developed acute renal failure with anuria and the necessity of repeated haemodialyses and severe acidosis of the mixed type on account of which he was intubated and switched to artificial ventilation. According to the case-history clinical and laboratory picture of the disease (extremely high creatine kinase activity, hyperkalaemia, acidosis, hepatorenal failure) malignant hyperthermia was suspected. After a single intravenous injection of sodium dantrolene, 2.5 mg/kg, the temperature dropped and within 24 hours the patient was afebrile. Gradually the acidosis improved, the blood pressure became stabilized and artificial ventilation was no longer used. The patient was discharged after 34 days in hospital in a state of cardiopulmonary compensation with mild polyuria but without signs of retention of nitrogenous substances with sideropenic anaemia and marginal creatine kinase and lactate dehydrogenase values. Within one month after discharge the laboratory values reached normal levels and only slight muscular weakness and greater fatiguability persisted.
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PMID:[An attack of malignant hyperthermia caused by a combination of the effects of succinylcholine, increased physical exertion and alcohol abuse]. 1095 47

3,4-Dichlorophenylhydroxylamine (3,4-CPHA) is the N-hydroxyl metabolite of 3,4-dichloroaniline. 3,4-Dichloroaniline is a breakdown product of the herbicide Propanil. Previous work has shown that 3,4-dichloroaniline is acutely toxic to the kidney and bladder. The purpose of this study was to examine the in vitro toxicity of 3,4-dichlorophenylhydroxylamine. Renal cortical slices were prepared from male Fischer 344 rats (190-250 g) and were incubated with 0-0.5 mM 3,4-CPHA for 30-120 min under oxygen and constant shaking. 3,4-CPHA produced a concentration and time dependent alteration in lactate dehydrogenase (LDH) leakage, organic ion accumulation and pyruvate stimulated gluconeogenesis. Glutathione levels were diminished within 60 min below control values by 0.1 and 0.5 mM 3,4-CPHA. A 30 min pretreatment with 0.1 mM deferoxamine did not alter 3,4-CPHA toxicity. Alterations in pyruvate stimulated gluconeogenesis and LDH leakage were comparable between vehicle and deferoxamine pretreated tissues. Other studies examined the effect of (1 mM) glutathione, 2 mM ascorbic acid and 1 mM dithiothreitol (DTT) on toxicity. Pretreatment for 30 min with vehicle or 1 mM DTT induced comparable changes in LDH leakage and pyruvate stimulated gluconeogenesis. Pretreatment for 30 min with 1 mM glutathione or 2 mM ascorbic acid reduced 3,4-CPHA toxicity. LDH leakage was not elevated as markedly in renal slices pretreated with glutathione relative to slices pretreated with vehicle. These results indicate that 3,4-CPHA toxicity is through an iron independent mechanism. 3,4-CPHA cytotoxicity was reduced by pretreatment with glutathione or ascorbic acid suggesting formation of a reactive intermediate.
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PMID:3,4-Dichlorophenylhydroxylamine cytotoxicity in renal cortical slices from Fischer 344 rats. 1136 11

Experimental infection of BALB/c mice with the Gram-positive bacterium Nocardia asteroides (strain GUH-2) results in life-long movement abnormalities including head shaking and spinning when held by the tail. The head shaking is temporarily inhibited by treatment with dopamine's precursor levodopa, suggesting that abnormalities in dopaminergic neurotransmission may be involved in these movement abnormalities. Cell-free filtrates from N. asteroides cultures induce > 70% dopamine depletion in rat pheochromocytoma PC12 cells, suggesting that Nocardia's effects on dopamine neurons may result in part from secreted factors. The nature of this dopamine-depleting activity was examined in the present study. Dopamine-depleting activity in N. asteroides culture filtrate was resistant to heat (100 degrees C x 30 min), proteases, and chloroform extraction, and was present in a low molecular mass (< 3 kDa) fraction. It was partially inhibited by decreasing (to 4.0) or increasing (to 10.0) the filtrate pH. GUH-2 filtrate increased cellular lactate dehydrogenase release by only 2%, and induced apoptotic morphology in only 11% of PC12 cells, suggesting that dopamine-depleting activity was not due to either cell injury or induction of apoptosis. These results suggest that a protease-resistant, low molecular mass substance secreted by N. asteroides may be responsible for its dopamine-depleting effects.
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PMID:Characterization of dopamine-depleting activity of Nocardia asteroides strain GUH-2 culture filtrate on PC12 cells. 1531 47

p-Aminophenol (PAP), a metabolite of acetaminophen, is nephrotoxic. This study investigated PAP-mediated changes as a function of time that occur prior to loss of membrane integrity. Experiments further evaluated the development of oxidative stress by PAP. Renal slices from male Fischer 344 (F344) rats (N = 4-6) were exposed to 0.1, 0.25, and 0.5 mM PAP for 15-120 min under oxygen and constant shaking at 37 degrees C. Pyruvate-stimulated gluconeogenesis, adenine nucleotide levels, and total glutathione (GSH) levels were diminished in a concentration- and time-dependent manner prior to detection of a rise in lactate dehydrogenase (LDH) leakage. Glutathione disulfide (GSSG) levels were increased by PAP suggesting the induction of oxidative stress. Western blot analysis confirmed a rise in 4-hydroxynonenal (4-HNE)-adducted proteins in tissues exposed to 0.1 and 0.25 mM PAP for 90 min. The appearance of 4-HNE-adducted proteins at the 0.1 mM concentration of PAP occurred prior to development of increased LDH leakage. Pretreatment with 1 mM glutathione (GSH) for 30 min only partially reduced PAP toxicity as LDH values were less severely depleted relative to tissues not pretreated with GSH. In contrast, pretreatment for 15 min with 2 mM ascorbic acid completely protected against PAP toxicity. Further studies showed that ascorbic acid pretreatment prevented PAP-mediated depletion of GSH. In summary, PAP rapidly depletes GSH and adenine nucleotides and inhibits gluconeogenesis prior to a rise in LDH leakage. PAP induces oxidative stress as indicated by an increase in GSSG and 4-HNE-adducted proteins. Ascorbic acid pretreatment prevents PAP toxicity by maintaining GSH status.
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PMID:Time-dependent effect of p-aminophenol (PAP) toxicity in renal slices and development of oxidative stress. 1627 24

Antisynthetase syndrome is a type of Idiopathic Inflammatory Myopathy (IIM) associated with anti-Jo1 antibody. Kennedy's disease or X-linked spinal and bulbar muscular atrophy (SBMA) is a rare neuromuscular disease. We describe the case report of a 53-year-old man who presented with proximal muscle weakness and a history of bilateral hand tremor. Initial physical examination demonstrated "mechanic's hands", Raynaud's phenomenon, having elevated creatine kinase and lactate dehydrogenase levels and anti-Jo1 antibody positivity. His muscle biopsy demonstrated inflammatory infiltrate characteristic of IIM. Considering these findings, we reached the diagnosis of antisynthetase syndrome and commenced immunosuppressive therapy. On follow-up examination, he had developed dysphagia, and his tremor had worsened. His electroneurogram result was characteristic of Kennedy's disease, and the genetic test result showed an allele with 44 CAG repeat expansion in the androgen receptor gene of the X chromosome. This confirmed that in addition to antisynthetase syndrome, he also had Kennedy's disease. This patient now receives immunology and neurology follow-up. His symptoms have improved with low dose corticosteroids, propranolol for tremor, vitamin B supplementation, and physiotherapy. This article presents a rare case report of a patient with concurrent antisynthetase syndrome and Kennedy's disease, both of which lead to elevated creatine kinase levels and muscle weakness, thus, underpinning the importance of careful follow-up of patients with IIM and maintaining an open mind to other diagnoses when faced with refractory and/or new symptoms.
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PMID:Rare association of antisynthetase syndrome and Kennedy's disease. 1859 36

Neuroblastoma cells, cultivated on plastic dishes, in presence of 15 mM glucose resist very well to hypoxia. Cells incubated on plastic dishes, if left unshaken, showed a Pasteur effect at an oxygen concentration below 10%. Oxygen diffusion was the limiting factor in these plastic dishes since improved oxygen diffusion, as a result of shaking, decreased the lactate production considerably at all oxygen concentrations used. When cells were cultivated on Petriperm((R)) dishes, coated with polylysine, oxygen diffusion was no longer a rate-limiting factor: less lactate was produced at 21% O(2) and hypoxia, down to 2.5% O(2) did not show any increase in the rate of lactate production, while Antimycin A drastically increased the glycolytic rate. A situation of limited oxygen availability resulted in two different kinds of adaptation of the neuroblastoma cells: first an instantaneous metabolic regulation leading to an increased glycolytic rate-the Pasteur effect-followed later by an increase in the activities of the glycolytic enzymes-hexokinase (EC 2.7.1.1), phosphoglucose isomerase (EC 5.3.1.9), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40) and lactate dehydrogenase (EC 1.1.1.27) and a simultaneous decrease of the mitochondrial cytochrome c oxidase (EC 1.9.3.1) activity. However, when the glucose concentration in the medium was decreased to 5 mM the cells were affected by hypoxia already at 5% O(2): cells released lactate dehydrogenase extracellularly and their protein content was decreased. This toxic effect of hypoxia was related to the exhaustion of the glucose supply.
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PMID:Effect of oxygen and glucose availability on the glycolytic rate in neuroblastoma cells under different conditions of culture. 2048 70

Idiopathic Parkinson's disease (PD) is a progressive neurodegenerative disorder, clinically manifested by cardinal motor symptoms including tremor at rest, bradykinesia, and muscle rigidity. Transplantation of dopaminergic (DAergic) neurons is an experimental therapy for PD, however, it is limited by suboptimal integration and low survival of grafts. Pretreatment of donor tissue may offer a strategy to improve properties of transplanted DAergic neurons and thereby clinical outcome. We have previously shown that a combination of neurotrophin-4/5 (NT-4/5) and glial cell line-derived neurotrophic factor (GDNF) demonstrated additive effects on rat ventral mesencephalic (VM) tissue. The present study investigated the effects of NT-4/5 and GDNF as single factors, or in combination on DAergic neurons, in organotypic explant cultures of fetal human ventral mesencephalon. For that purpose, free-floating roller-tube cultures were prepared from VM and the equally sized pieces grown for 1 week in the presence or absence of neurotrophic factors. Both neurotrophic factors increased dopamine content in the culture medium and in the number of tyrosine hydroxylase immunoreactive neurons, most prominently after combined GDNF + NT-4/5 treatment. Culture volumes did not differ between groups while content of lactate dehydrogenase in the culture medium was moderately reduced in all treated groups. In conclusion, we identified that a combination of GDNF and NT-4/5 robustly promoted differentiation and survival of human fetal VM DAergic neurons, an observation with potential promising impact for cell replacement approaches in PD.
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PMID:A Combination of NT-4/5 and GDNF Is Favorable for Cultured Human Nigral Neural Progenitor Cells. 2970 Oct 77


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