The outcomes of laparoscopic omentum-preserving gastrectomy compared to open surgery with omentectomy in gastric cancer patients: a propensity score matched study of 249 UICC stage 0-IV gastric cancer patients.

BACKGROUND: We performed a propensity score matched study comparing patients' short- and long-term results after laparoscopic omentum-preserving gastrectomy and open surgery with omentectomy with UICC stages 0-IV. METHODS: Between 2015 and 2022, 311 patients with gastric cancer underwent surgery at the University Clinical Centre Maribor. Of these, 249 met the inclusion criteria and 198 were included in the study group after PSM. RESULTS: Patients in both groups were well-balanced in demographic and pathological characteristics after PSM. There was no significant difference in the 5-year survival between groups (LAP: 62.2% vs. OPN: 54.4%; p = 0.950). The Cox regression model identified UICC stage and age as significant predictors for survival. In both groups, peritoneal dissemination was the most common site of recurrence. The multivariate analysis identified the UICC stage as a significant predictor for peritoneal recurrence, while omental preservation was not associated with a higher risk of peritoneal dissemination. Omentum preservation was not associated with more intestinal obstruction. Patients in the LAP group had significantly shorter hospital stays (LAP: 9(6) vs. OPN: 10(5); p = 0.009), less postoperative morbidity (LAP: 17% vs. OPN: 23.4%; p = 0.009), and significantly more extracted LNs per operation compared to open surgery (LAP: 31 ± 11 LNs vs. OPN: 25 ± 12 LNs; p = 0.002). CONCLUSION: Based on our results, we recommend the use of laparoscopic omentum-preserving gastrectomy in patients with early and advanced gastric cancer.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.

Evaluation of focused sentinel lymph node RT-qPCR screening for micrometastases with the use of the Maruyama computer program.

BACKGROUND: In this preliminary study, we investigated the sensitivity and specificity of reverse transcriptase (RT)-qPCR lymph node (LN) metastases detection, the accuracy of intraoperative dye navigation, and the incidence of micrometastasis (MM) detection with this protocol, compared to other published studies. METHODS: A total of 23 patients were enrolled in the study. The first stained LN was analyzed using RT-qPCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) expression, as markers for MM involvement. The Maruyama computer program was used to determine the most likely first metastatic site. These results were compared with the actual staining patterns to evaluate whether the first draining LN was extracted. We analyzed the correlations between MM and tumor characteristics. The incidence of MM detected with the present method was compared to other studies, as markers of the accuracy of the present protocol. RESULTS: At 35 threshold cycles, the RT-qPCR had a negative predictive value of 100 % and a positive predictive value of 83.3 %. MM were detected in 4 out of 14 node-negative patients (28.6 %). The extracted sentinel LN coincided in 76.9 % of cases with the most probable first metastatic LN predicted by the Maruyama program. MM were found more frequently in these 'high-risk' LNs. Significant differences were found in the Lauren's histological type distribution and the age distribution among the MM-positive and MM-negative groups. CONCLUSION: Our preliminary results confirm that RT-qPCR is an accurate method of MM detection, that the dye navigation enables the determination of the first draining LN, and that the incidence of MM detection with this focused sentinel LN protocol is comparable to other studies.

Neuropsychological assessment at school-age and prenatal low-level exposure to mercury through fish consumption in an Italian birth cohort living near a contaminated site.

The relative effects of prenatal and postnatal low-level mercury exposure and fish intake on child neurodevelopment are still controversial. Limited evidence is available from Mediterranean populations. In this prospective study, we measured the Verbal and Performance IQ in Italian children at school-age who were resident in an area declared as a National contaminated site because of mercury pollution, taking into account the possible beneficial effect of fish consumption and potential confounders. A mother-child cohort made up of 242 children was established at birth in Northeastern Italy in 2001. Their mothers were interviewed approximately 2 months after delivery to determine type, quantity, and origin of fish consumed during pregnancy and about a number of mother, child and family characteristics. Total mercury (THg) and methyl mercury (MeHg) were assessed in maternal hair and breast milk and in the child's hair. When children reached 7-9 years of age, 154 (63.6%) parents gave consent to participate in a follow-up evaluation. On that occasion, a child's hair sample was collected to determine the current concentration of THg, mothers were asked to complete a self-administered questionnaire, and children underwent neuropsychological testing. Verbal IQ, performance IQ and full scale IQ were measured by the Wechsler Intelligence Scale for Children (WISC III) administered by psychologists at school or local health centers. Demographic, socioeconomic and lifestyle information, medical information of the child's family and the child's dietary habits were collected using a questionnaire filled in by mothers. Multivariable linear regression models were used to evaluate the association between prenatal THg exposure through fish consumption of mothers in pregnancy and children's IQ after adjustment for possible confounders such as fish consumption of mothers in pregnancy, child's fish consumption at follow-up, child's birthweight, maternal cigarette smoking during pregnancy, house size and property place of residence during pregnancy and gender. THg in the child's hair at 7 years of age was fairly correlated with THg in maternal hair at delivery (rs=0.35; p<0.0001) and was strongly correlated with child's seafood consumption (rs=0.50, p<0.0001). No differences in maternal THg levels were found when comparing children with low or extremely low or high or extremely high scores vs others, considering separately full scale, verbal, and performance IQs. Children born from mothers with hair THg levels greater than or equal to 2000ng/g had full scale, verbal and performance IQs which were 4-5 points lower than children born from women with lower THg levels, but these differences were not statistically significant. Fresh fish intake of mothers in pregnancy was slightly positively associated with full scale and performance but not so with verbal IQs. Canned fish showed to be negatively associated with all the outcome variables. Unexpectedly, children born to mothers from one town showed IQ scores significantly lower than the other children; however, none of the many variables considered in these analyses could explain this result. The relatively low Hg levels found in the biological samples did not provide evidence of high and extensive Hg exposure in this population. Although THg levels in maternal and child's biological samples are correlated with fish consumption, the effects of THg and fish on neurological outcomes go in opposite directions. These results do not allow to develop recommendations regarding fish consumption in pregnancy but suggest that keeping THg hair levels<2000ng/g might be desirable.

Evaluation of a focused sentinel lymph node protocol in node-negative gastric cancer patients.

BACKGROUND/AIMS: A specific preoperative work-up was used to access a limited number of high-risk lymph nodes with RT-qPCR for micrometastatic sentinel lymph node involvement. We validated our protocol with IHC screening for micrometastases and long-term survival analysis. METHODOLOGY: From the 32 patients included 22 were node-negative patients. With a specific preoperative protocol sentinel lymph nodes (1-2 per patient) were extracted for further RT-qPCR analysis for CEA and CK20 expression. In 10 patients from the study group, the remaining lymph nodes around the extracted sentinel lymph node from the first compartment were additionally screened using IHC for missed micrometastases. RESULTS: Micrometastases were detected in seven of 22 (31.8%) node-negative patients. RT-qPCR identified micrometastases in four of 10 haematoxylin-eosin-negative lymph nodes (40%), and in three of eight IHC negative lymph nodes (37.5%). The cumulative 3-year survival for the study group was 80.8%. The 3-year survival in the RT-qPCR-negative group was 90%, compared with 66.7% in the RT-qPCR-positive group (p=0.289). CONCLUSIONS: Encouraged by these results, we will include more patients in our focused sentinel lymph node protocol. With a refinement of our method, we believe the focused sentinel lymph node protocol can be implemented for intraoperative tailoring of extent of lymphadenectomy.

SU-E-J-106: Atlas-Based Segmentation: Evaluation of a Multi-Atlas Approach for Lung Cancer.

PURPOSE: Previous studies have shown atlas-based segmentation using a single best matched (SBM) atlas subject can significantly reduce contouring time. A new multi-atlas approach has been shown to provide greater accuracy than SBM for cancer of the head and neck. The goal of this study was to evaluate the multi-atlas technique for lung cancer treatment planning. METHODS: An institution's SBRT lung atlas containing 82 subjects was utilized for atlas segmentation. Each atlas subject contained manually defined contours of the esophagus, cord, heart, left lung, right lung, and trachea. CT scans and contours for 16 subjects were evaluated. SBM used the one automatically determined best match for segmentation. Multi-atlas used multiple automatically determined best matches: 3, 4, and 5, respectively. The final segmentation for multi-atlas was generated using Majority Vote which comprises the area of overlap for at least half of the individual segmentations (2 of 3, 2 of 4, and 3 of 5, respectively). Average Dice Similarity Coefficients (DSC) were calculated for each structure to compare against manually defined 'gold' standard contours for that subject. Overall percent improvement was calculated as the proportion of the error corrected by the method, or % difference on 1-DSC. RESULTS: All multi-atlas methods were significantly more accurate than SBM (p-value < 0.0005) with average DSC of 0.802 +/- 0.172, 0.809 +/ 0.163, 0.802 +/- 0.182 respectively for Multi-3, Multi-4, and Multi-5 compared to 0.773 +/- 0.187 for SBM. No significant differences existed between the different multi-atlas approaches. Overall, Multi-4 showed the greatest improvement over SBM with 16% improvement followed by Multi-3 and Multi-5 at 12%. CONCLUSIONS: Each multi-atlas approach resulted in significantly more accurate contours compared to the SBM. While still requiring some editing, this method for segmentation using multiple atlases shows promise for further decreasing the contouring time required for lung cancer. MIM Software Inc.

Macromolecular prodrugs XI. Synthesis and characterization of polymer-estradiol conjugate.

Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl-DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.

Periprostatic local anesthesia eliminates pain of office-based transrectal prostate biopsy.

Up to 96% of patient who undergo prostate biopsy report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core biopsies were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy.A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P<0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic prostatectomy following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result.

Mercury, selenium, and cadmium in human autopsy samples from Idrija residents and mercury mine workers.

Total Hg and Se concentrations were determined in autopsy samples of retired Idrija mercury mine workers, Idrija residents living in a Hg-contaminated environment, and a control group with no known Hg exposure from the environment. In selected samples we also checked the presence of MeHg. The highest Hg concentrations were found in endocrine glands and kidney cortex, regardless of the group. MeHg contributed only to a negligible degree to the total mercury concentrations in all analyzed samples. In the Hg-exposed groups the coaccumulation and retention of mercury and selenium was confirmed. Selenium coaccumulation with a Hg/Se molar ratio near 1 or higher was notable only in those tissue samples (thyroid, pituitary, kidney cortex, nucleus dentatus) where the mercury concentrations were >1 microg/g. After tissue separation of such samples the majority of these elements were found in the cell pellet. Because the general population is continuously exposed to Cd and possibly also to Pb from water, food, and/or air, in some samples the levels of these elements were also followed. In all examined control tissue samples the average values of Cd (kidney cortex, thyroid, hippocampus, cortex cerebellum, nucleus dentatus) and Pb (thyroid, hippocampus) exceeded the average values of Hg. Cd concentrations were the highest, particularly in kidney cortex and thyroids (microg/g), but no relationship between Cd and Se concentration was evident at the tissue level. Regarding the results in the control group, it is debatable which element is the more hazardous for the general population as concerns neurotoxicity.

Effects of PDH activation by dichloroacetate in human skeletal muscle during exercise in hypoxia.

During the onset of exercise in hypoxia, the increased lactate accumulation is associated with a delayed activation of pyruvate dehydrogenase (PDH; Parolin ML, Spreit LL, Hultman E, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Am J Physiol Endocrinol Metab 278: E522-E534, 2000). The present study investigated whether activation of PDH with dichloroacetate (DCA) before exercise would reduce lactate accumulation during exercise in acute hypoxia by increasing oxidative phosphorylation. Six subjects cycled on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake after a saline (control) or DCA infusion while breathing 11% O(2). Muscle biopsies of the vastus lateralis were taken at rest and after 1 and 15 min of exercise. DCA increased PDH activity at rest and at 1 min of exercise, resulting in increased acetyl-CoA concentration and acetylcarnitine concentration at rest and at 1 min. In the first minute of exercise, there was a trend toward a lower phosphocreatine (PCr) breakdown with DCA compared with control. Glycogenolysis was lower with DCA, resulting in reduced lactate concentration ([lactate]), despite similar phosphorylase a mole fractions and posttransformational regulators. During the subsequent 14 min of exercise, PDH activity was similar, whereas PCr breakdown and muscle [lactate] were reduced with DCA. Glycogenolysis was lower with DCA, despite similar mole fractions of phosphorylase a, and was due to reduced posttransformational regulators. The results from the present study support the hypothesis that lactate production is due in part to metabolic inertia and cannot solely be explained by an oxygen limitation, even under conditions of acute hypoxia.

Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia.

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O(2) (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free P(i), in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDH(a)) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [P(i)]. At the end of exercise, PDH(a) was greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.

Effect of induced metabolic alkalosis on human skeletal muscle metabolism during exercise.

The purpose of the study was to examine the roles of active pyruvate dehydrogenase (PDH(a)), glycogen phosphorylase (Phos), and their regulators in lactate (Lac(-)) metabolism during incremental exercise after ingestion of 0.3 g/kg of either NaHCO(3) [metabolic alkalosis (ALK)] or CaCO(3) [control (CON)]. Subjects (n = 8) were studied at rest, rest postingestion, and during constant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O(2) uptake (VO(2 max)). Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ALK resulted in significantly (P < 0.05) higher intramuscular Lac(-) concentration ([Lac(-)]; ALK 72.8 vs. CON 65.2 mmol/kg dry wt), arterial whole blood [Lac(-)] (ALK 8.7 vs. CON 7.0 mmol/l), and leg Lac(-) efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75% VO(2 max). The increased intramuscular [Lac(-)] resulted from increased pyruvate production due to stimulation of glycogenolysis at the level of Phos a and phosphofructokinase due to allosteric regulation mediated by increased free ADP (ADP(f)), free AMP (AMP(f)), and free P(i) concentrations. PDH(a) increased with ALK at 60% VO(2 max) but was similar to CON at 75% VO(2 max). The increased PDH(a) may have resulted from alterations in the acetyl-CoA, ADP(f), pyruvate, NADH, and H(+) concentrations leading to a lower relative activity of PDH kinase, whereas the similar values at 75% VO(2 max) may have reflected maximal activation. The results demonstrate that imposed metabolic alkalosis in skeletal muscle results in acceleration of glycogenolysis at the level of Phos relative to maximal PDH activation, resulting in a mismatch between the rates of pyruvate production and oxidation resulting in an increase in Lac(-) production.

Mercury and other elements in lichens near the INA Naftaplin gas treatment plant, Molve, Croatia.

This paper describes the use of epiphytic lichens as bioindicators for spatial monitoring of mercury and other elements in air near the natural gas treatment facilities at Molve, Croatia. It is well known that at this location the concentration of mercury in natural gas is very high and therefore it has to be removed from natural gas before further processing in order to prevent technological and environmental problems. In order to monitor the efficiency of an industrial facility for removal of mercury from natural gas, mercury measurements in air and lichens were performed during 9 months in 1997/1998. In situ lichens Parmelia sulcata, Xantoria parientina and Hypogymnia physodes and transplanted lichen species Hypogymnia physodes were used. A good correlation between mercury concentrations in air and lichens was found. The concentrations of barium and bromium were also significantly elevated in transplanted lichens, most probably related to technological process at the gas treatment plant and/or other geological factors. It was confirmed that lichens can successfully be used as bioindicators, provided a careful experiment is designed, particularly the amount of lichens transplanted, the duration of exposure and the initial levels and homogeneity of transplanted lichens.

Determination of mercury in crude oil by in-situ thermal decomposition using a simple lab built system.

A simple system based on thermal decomposition for the one step determination of mercury has been built. This system was applied to the analysis of crude oil and related products. Samples were directly introduced into the system without the use of chemicals and digestion procedures. After 4 min, matrices and mercury compounds were decomposed, and elemental mercury was collected on a gold sand trap, and then detected by atomic fluorescence spectroscopy (AFS). In principle, any sample can be analyzed by this method provided the sample can be introduced into the system quantitatively. The method detection limit was approximately 0.2 ng/g for 0.04 g of crude oil introduced to the system. Various other samples including, biological, environmental, and general merchandise have been analyzed. Results obtained have been compared with established traditional methods including radiochemical neutron activation analysis (RNAA). Good agreement of results between methods was found. Recoveries were close to 100% for certified reference materials. Results were independent of mercury species and sample types.

Profound circulatory shock following heroin overdose.

A 17-year-old previously healthy girl with profound circulatory shock following a heroin overdose is reported. Except for opiates no other substances and specifically no cocaine were found in the blood and urine samples. Even though the mechanism of shock is not completely understood, severe depression of left ventricular contractility seems to be the predominant reason. Acute right heart failure with decreased pulmonary capillary wedge pressure and arterial vasodilatation resulting in maldistribution of cardiac output cannot be ruled out as possible contributing factors. The shock was successfully reversed with volume loading and a high dose of dobutamine. The recovery was uneventful and the patient was discharged with normal cardiac function.

Comparison of porcine hepatocytes with human hepatoma (C3A) cells for use in a bioartificial liver support system.

Cells from primary porcine hepatocytes (PPH) and the immortalized human hepatoma cell line C3A are both used in bioartificial liver support systems (BALSS). In this work the viability and metabolic capacity of PPH and C3A cells cultured in different media were compared. Also, because the cells come into direct or indirect contact with human blood components in BALSS, the effects of human complement on survival and functions of the cells was evaluated. For short-term culture, maintenance of PPH viability was essential for retention of P450IA1 activity (r = 0.882, p < 0.01) and effective ammonia clearance (r = -0.791, p < 0.01). When cell viability was below 60% P450IA1 activity could not be recorded and nitrogen elimination activity significantly diminished. In contrast to PPH, ammonia levels were markedly increased for C3A cells in all culture media tested (p < 0.01). Ammonia increase correlated with C3A viability (r = 0.896, p < 0.05). PPH metabolic function was superior to that of the C3A cell line when evaluated by P450IA1 activity, ammonia removal, and amino acid metabolism. When PPH were incubated in human plasma (HP) or human serum (HS) there was rapid and irreversible deterioration of viability occurring within 9 h. This toxic effect could be prevented by the inactivation of complement. When sodium citrate dissolved in dextrose was added to medium, there was considerable damage to both PPH and the C3A cell line. However, there was no demonstrable toxic effect when hepatic cells of either type were exposed to heparin. We conclude that PPH cultivated in complement-inactivated HP or HS are to be preferred to C3A for clinical application of BALSS, and that heparin should be preferred for anticoagulation in BALSS.

Effects of short-term submaximal training in humans on muscle metabolism in exercise.

Muscle metabolism, including the role of pyruvate dehydrogenase (PDH) in muscle lactate (Lac-) production, was examined during incremental exercise before and after 7 days of submaximal training on a cycle ergometer [2 h daily at 60% peak O2 uptake (VO2 max)]. Subjects were studied at rest and during continuous steady-state cycling at three stages (15 min each): 30, 65, and 75% of the pretraining VO2 max. Blood was sampled from brachial artery and femoral vein, and leg blood flow was measured by thermodilution. Biopsies of the vastus lateralis were obtained at rest and during steady-state exercise at the end of each stage. VO2 max, leg O2 uptake, and the maximum activities of citrate synthase and PDH were not altered by training; muscle glycogen concentration was higher. During rest and cycling at 30% VO2 max, muscle Lac- concentration ([Lac-]) and leg efflux were similar. At 65% VO2 max, muscle [Lac-] was lower (11.9 +/- 3.2 vs. 20.0 +/- 5.8 mmol/kg dry wt) and Lac- efflux was less [-0.22 +/- 0.24 (one leg) vs. 1.42 +/- 0.33 mmol/min] after training. Similarly, at 75% VO2 max, lower muscle [Lac-] (17.2 +/- 4.4 vs. 45.2 +/- 6.6 mmol/kg dry wt) accompanied less release (0.41 +/- 0.53 vs. 1.32 +/- 0.65 mmol/min) after training. PDH in its active form (PDHa) was not different between conditions. Calculated pyruvate production at 75% VO2 max fell by 33%, pyruvate reduction to lactate fell by 59%, and pyruvate oxidation fell by 24% compared with before training. Muscle contents of coenzyme A and phosphocreatine were higher during exercise after training. Lower muscle lactate production after training resulted from improved matching of glycolytic and PDHa fluxes, independently of changes in muscle O2 consumption, and was associated with greater phosphorylation potential.