INTRODUCTION AND OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH(4) and LDH(5) are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD.
PATIENTS AND METHODS: Eighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers.
RESULTS: Controls and patients had similar concentrations of total LDH (mean [SE], 130 [30]micromol/min/g vs 152 [50]micromol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH(1), LDH(2), and LDH(3), with decreased LDH(5) levels; these patients were women and had a lower oxygen saturation. The LDH(5) level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH(3) and LDH(4) concentrations whereas type IIX fibers were inversely correlated with LDH(3) concentration.
CONCLUSION: Measurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism.
Sección de Adaptación Muscular, Instituto de Medicina Experimental, Universidad Central de Venezuela, Caracas, Venezuela
Thursday
Lactate dehydrogenase isozymes in skeletal muscle of patients with chronic obstructive pulmonary disease]
Friday
Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors
BACKGROUND: Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of Lactate-dehydrogenase-5 (LDH-5) in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma.
METHODS: LDH-5 expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1alpha (HIF-1alpha) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.
RESULTS: There were 94 cases (61.8%) showing high LDH-5 expression, and 95 patients (62.5%) had high HIF-1alpha expression. Positive correlation was found between LDH-5 expression and HIF-1alpha, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1alpha expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.
CONCLUSION: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
METHODS: LDH-5 expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1alpha (HIF-1alpha) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.
RESULTS: There were 94 cases (61.8%) showing high LDH-5 expression, and 95 patients (62.5%) had high HIF-1alpha expression. Positive correlation was found between LDH-5 expression and HIF-1alpha, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1alpha expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.
CONCLUSION: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
Multipurpose peptide tags for protein isolation
A multifunctional peptide tag (HYDHYD) consisting of histidine, tyrosine and aspartate residues was fused to the N-terminal ends of green fluorescent protein (GFP), lactate dehydrogenase (LDH) and "http://www.leebio.com/products.php?search=hemoglobin">human hemoglobin (Hb), proteins which were subjected to ion-exchange chromatography (IEC), aqueous two-phase system partition, immobilized metal-ion affinity chromatography (IMAC), and hydrophobic interaction chromatography (HIC). Tagged GFP was retained significantly longer (>1 column volume) in both HIC and IEC. It exhibited 3× greater partition in favor of the hydrophobic phase in a two-phase system and 96% could be bound to an IMAC column which did not bind native GFP.
ARTICLE
ARTICLE
Thursday
A Nitric Oxide–Inducible Lactate Dehydrogenase Enables Staphylococcus aureus to Resist Innate Immunity
Staphylococcus aureus is one of the most successful human pathogens, colonizing 2 billion individuals worldwide and causing invasive infections even in immunocompetent hosts. S. aureus can evade multiple components of host innate immunity, including the antimicrobial radical nitric oxide (NO) produced by activated phagocytes. We show that S. aureus is capable of metabolically adapting to nitrosative stress by expressing an NO-inducible L-lactate dehydrogenase (ldh1, SACOL0222) divergently transcribed from the NO-detoxifying flavohemoglobin (hmp). L-Lactate production allows S. aureus to maintain redox homeostasis during nitrosative stress and is essential for virulence. NO-inducible lactate dehydrogenase activity and NO resistance distinguish S. aureus from the closely related commensal species S. epidermidis and S. saprophyticus.
Tuesday
A bioassay for the simultaneous measurement of metabolic activity, membrane integrity, and lysosomal activity in cell cultures
The aim of this study was the development of an in vitro bioassay that combines several endpoints of general cytotoxicity for the screening of compounds or mixtures of compounds with potential bioactivity. The Alamar Blue assay was employed to assess metabolic activity, the Neutral Red assay was used for the assessment of membrane function and lysosomal activity, and the lactate dehydrogenase leakage assay was employed for the assessment of membrane integrity. Each assay was performed separately and in combination using a human fibroblast cell line (MRC-5). Three fungal secondary metabolites of different chemistry that affect different cellular targets were tested as model compounds: deoxynivalenol, enniatin B1, and 2-amino-14,16-dimethyloctadecan-3-ol. The obtained inhibitive compound concentrations for the assays performed separately and in combination were not significantly different (P < 0.05, n = 9). The combination of several cytotoxicity endpoints in a single assay increases the chance that potential bioactive/cytotoxic compounds are discovered during the screening of mixtures of natural compounds (e.g., extracts from fungal cultures or plants) when one endpoint fails and, at the same time, might give some basic information on the cellular target.
ARTICLE
ARTICLE
Friday
Lactate Dehydrogenase-5 (LDH-5) Expression in Human Gastric Cancer: Association with Hypoxia-Inducible Factor (HIF-1alpha) Pathway, Angiogenic Factors
BACKGROUND:
Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma.
METHODS:
Lactate-dehydrogenase-5 (LDH-5) expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1alpha (HIF-1alpha) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.
RESULTS: There were 94 cases (61.8%) showing high Lactate-dehydrogenase-5 (LDH-5) expression, and 95 patients (62.5%) had high HIF-1alpha expression. Positive correlation was found between LDH-5 expression and HIF-1alpha, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1alpha expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.
CONCLUSION: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma.
METHODS:
Lactate-dehydrogenase-5 (LDH-5) expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1alpha (HIF-1alpha) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.
RESULTS: There were 94 cases (61.8%) showing high Lactate-dehydrogenase-5 (LDH-5) expression, and 95 patients (62.5%) had high HIF-1alpha expression. Positive correlation was found between LDH-5 expression and HIF-1alpha, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1alpha expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.
CONCLUSION: The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
Tuesday
Sport-related hyperhomocysteinemia: a putative marker of muscular demand to be noticed for cardiovascular risk.
OBJECTIVE: Regular physical activity is associated with a reduction of cardiovascular morbidity and mortality, however, evidences of unfortunate cardiovascular events , accompanying elite sport involvement, continue to accumulate. To date, no information are available upon possible peculiarities of the cardiovascular risk profile in athletes.
DESIGN: The aim of this study was to evaluate plasma homocysteine levels in a group of athletes and to search for relationship with vitamin status and other metabolic variables in order to confirm the existence of a "sport-related hyperhomocysteinemia" and to explain its clinical significance. The study population was composed by 82 athletes (59M and 23F) practising different sports and 70 healthy age matched subjects (40M and 30F) as control group. Besides the general clinical and analytical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol , Lactate dehydrogenase (LDH) , Creatine Kinase (CPK) and IL-6.
RESULTS: The prevalence of hyperhomocysteinemia (>15 micromol/L) in athletes and controls was 47 % and 15 %, respectively. No correlation was found between homocysteine and all the other investigated variables, in particular plasma folate, blood pressure, Lactate Dehydrogenase LDH, CPK total , total and HDL cholesterol and IL-6.
CONCLUSION: The results of this study confirm the existence of a sport-related hyperhomocysteinemia which appears linked neither to the same variables found in the general population, nor to specific training-related variables. We suggest that it would represent an adaptation to training but the possibility of a secondary vascular damage cannot be excluded.
Br J Sports Med. 2008 Jan 23
DESIGN: The aim of this study was to evaluate plasma homocysteine levels in a group of athletes and to search for relationship with vitamin status and other metabolic variables in order to confirm the existence of a "sport-related hyperhomocysteinemia" and to explain its clinical significance. The study population was composed by 82 athletes (59M and 23F) practising different sports and 70 healthy age matched subjects (40M and 30F) as control group. Besides the general clinical and analytical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol , Lactate dehydrogenase (LDH) , Creatine Kinase (CPK) and IL-6.
RESULTS: The prevalence of hyperhomocysteinemia (>15 micromol/L) in athletes and controls was 47 % and 15 %, respectively. No correlation was found between homocysteine and all the other investigated variables, in particular plasma folate, blood pressure, Lactate Dehydrogenase LDH, CPK total , total and HDL cholesterol and IL-6.
CONCLUSION: The results of this study confirm the existence of a sport-related hyperhomocysteinemia which appears linked neither to the same variables found in the general population, nor to specific training-related variables. We suggest that it would represent an adaptation to training but the possibility of a secondary vascular damage cannot be excluded.
Br J Sports Med. 2008 Jan 23
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