JOURNAL OF PHYCOLOGY, Issue 2 2007
T. Alwyn
Marine phytoplankton and macroalgae acquire important resources, such as inorganic nitrogen, from the surrounding seawater by uptake across their entire surface area. Rates of ammonium and nitrate uptake per unit surface area were remarkably similar for both marine phytoplankton and macroalgae at low external concentrations. At an external concentration of 1 ,M, the mean rate of nitrogen uptake was 10±2 nmol·cm,2·h,1 (n=36). There was a strong negative relationship between log surface area:volume (SA:V) quotient and log nitrogen content per cm2 of surface (slope=,0.77), but a positive relationship between log SA:V and log maximum specific growth rate (,max; slope=0.46). There was a strong negative relationship between log SA:V and log measured rate of ammonium assimilation per cm2 of surface, but the slope (,0.49) was steeper than that required to sustain ,max (,0.31). Calculated rates of ammonium assimilation required to sustain growth rates measured in natural populations were similar for both marine phytoplankton and macroalgae with an overall mean of 6.2±1.4 nmol·cm,2·h,1 (n=15). These values were similar to maximum rates of ammonium assimilation in phytoplankton with high SA:V, but the values for algae with low SA:V were substantially less than the maximum rate of ammonium assimilation. This suggests that the growth rates of both marine phytoplankton and macroalgae in nature are often constrained by rates of uptake and assimilation of nutrients per cm2 surface area. [source]

Greater growth hormone and insulin response in women than in men during repeated bouts of sprint exercise

ACTA PHYSIOLOGICA, Issue 2 2009
M. Esbjörnsson
Abstract Aim:, In a previous study, sprint training has been shown to increase muscle cross-sectional area in women but not in men [Eur J Appl Physiol Occup Physiol 74 (1996) 375]. We hypothesized that sprint exercise induces a different hormonal response in women than in men. Such a difference may contribute to explaining the observed gender difference in training response. Method:, Metabolic and hormonal response to three 30-s sprints with 20-min rest between the sprints was studied in 18 physically active men and women. Results:, Accumulation of blood lactate [interaction term gender (g) × time (t): P = 0.022], and plasma ammonia (g × t: P < 0.001) after sprint exercise was greater in men. Serum insulin increased after sprint exercise more so in women than in men (g × t: P = 0.020), while plasma glucose increased in men, but not in women (g × t: P < 0.001). Serum growth hormone (GH) increased in both women and men reaching similar peak levels, but with different time courses. In women the peak serum GH level was observed after sprint 1, whereas in men the peak was observed after sprint 3 (g × t; P < 0.001). Serum testosterone tended to decrease in men and increase in women (g × t: P = 0.065). Serum cortisol increased approx. 10,15% after sprint exercise, independent of gender (time: P = 0.005). Conclusion:, Women elicited a greater response of serum GH and insulin to sprint exercise. This may contribute to explaining the earlier observed muscle hypertrophy in women in response to sprint training. [source]

Metabolic, endocrine and haemodynamic risk factors in the patient with peripheral arterial disease

DIABETES OBESITY & METABOLISM, Issue 2002
Jill J. F. Belch
The morbidity and mortality associated with peripheral arterial disease (PAD) creates a huge burden in terms of costs both to the patient and to the health service. PAD is a deleterious and progressive condition that causes a marked increase in the risk of cardiovascular and cerebrovascular events. Further, PAD has a major negative impact on quality of life and mortality, and is associated with an increased risk of limb amputation. The clinical profile of patients at risk of PAD overlaps considerably with the known cardiovascular risk factors. These include, increasing age, smoking habit, diabetes, hypertension, dyslipidaemia, male sex and hyperhomocysteinaemia. For women, hormone replacement therapy appears to be associated with a reduced risk of PAD. Published PAD guidelines recommend aggressive management of risk factors, stressing the importance of lifestyle modification, antiplatelet agents, treating dyslipidaemia and diabetes. However, a large number of patients with PAD go undetected, either because they do not report their symptoms or because they are asymptomatic. It is therefore important to improve detection rates so that these patients can receive appropriate risk factor management. [source]

Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertension

DIABETES OBESITY & METABOLISM, Issue 5 2001
M. H. Uehara
SUMMARY Background Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p <,0.05), although HbA1c had decreased in both groups (PG: 6.7±3.0 to 5.9±2.6%; MG: 5.3±1.5 to 4.6±0.9%; p <,0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7±8.0 to 99.2±9.3 mmHg, p <,0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0±62.4 to 38.0±23.0 pmol/l, p <,0.05) and the insulin resistance index (3.5±2.7 to 1.8±1.0, p <,0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8±7.9 to 21.4±14.6 ,g/l; MG: 18.5±10.3 to 18.4±8.9 ,g/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels. [source]

Therapeutic targets in the management of Type 1 diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2002
P. D. Home
Abstract For historical reasons, diabetes has long been linked with blood and urine glucose control, partly because these were clearly linked to acute symptoms, and partly because glucose became measurable around 200 years ago. Today it is recognized that there is far more to diabetes than simply monitoring symptoms and blood glucose. Intensive management has an impact on the quality of life. Late complications have their own risk factors and markers. Monitoring and early detection of these risk factors and markers can lead to changes in treatment before tissue damage is too severe. Accordingly, professionals now find themselves monitoring a range of adverse outcomes, markers for adverse outcomes, risk factors and risk markers for microvascular and arterial disease, acute complications of therapy, and the care structures needed to deliver this. Adverse outcomes lend themselves to targets for complication control in populations, and markers of adverse outcomes (such as retinopathy and raised albumin excretion rate) in treatment cohorts. Surveillance systems will have targets for yearly recall and review of early complications. Metabolic (surrogate) outcomes can be monitored in individual patients, but monitoring is only of value in so far as it guides interventions, and this requires comparison to some intervention level or absolute target. Even for blood glucose control this is not easy, for conventional measures such as glycated haemoglobin have their own problems, and more modern approaches such as post-prandial glucose levels are controversial and less convenient to measure. In many people with type 1 diabetes targets for blood pressure, LDL cholesterol, and serum triglycerides will also be appropriate, and need to be part of any protocol of management. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Pharmacodynamics and pharmacokinetics of YM128, a GPIIb/IIIa antagonist prodrug

DRUG DEVELOPMENT RESEARCH, Issue 3 2002
Ken-ichi Suzuki
Abstract We examined the biochemical properties of YM-57029 ({4-[4-(4-Carbamimidoylphenyl)-3-oxopiperazin-1-yl]piperidino}acetic acid monohydrochloride trihydrate) and the pharmacodynamics and pharmacokinetics of its prodrug, YM128 (Ethyl (Z)-(4-{4-[4-(N2 -hydroxycarbamimidoyl)phenyl]-3-oxopiperazin-1-yl}piperidino)acetate), an orally-active glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist. YM-57029 strongly inhibited aggregation of human platelets induced by various agonists, with IC50 values ranging from 3.6 to 51 nM. YM-57029 specifically inhibited fibrinogen binding to purified GPIIb/IIIa about 1,000-fold more potently than Arg-Gly-Asp-Ser (RGDS). Moreover, YM-57029 effectively inhibited an Arg-Gly-Asp (RGD) peptide binding to platelets, suggesting that YM-57029 competed with the RGD sequence of ligand. YM-57029 or YM128 dose-dependently inhibited ex vivo platelet aggregation after iv bolus injection or oral administration to beagle dogs and cynomolgus monkeys. However, YM128 exerted more potent and prolonged inhibitory effects on platelet aggregation than YM-57029 after oral administration to cynomolgus monkeys. Furthermore, YM-57029 prolonged template bleeding time at a dose that inhibited ex vivo platelet aggregation during cumulative iv infusion to cynomolgus monkeys. Metabolic and pharmacokinetic studies showed that YM128 effectively converted into YM-57029 in liver microsomes from humans as well as dogs and monkeys, and that bioavailabilities of YM128 in dogs and monkeys were 32.3 and 22.2%, respectively. These results suggest that YM128, a prodrug of YM-57029, may be a valuable GPIIb/IIIa antagonist with good bioavailability in humans. Drug Dev. Res. 55:149,161, 2002. © 2002 Wiley-Liss, Inc. [source]

Expression of STAMP2 in monocytes associates with cardiovascular alterations

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2010
Zhi-Hao Wang
Eur J Clin Invest 2010; 40 (6): 490,496 Abstract Background, Metabolic and inflammatory pathways crosstalk at many levels. In this study, we aimed to investigate the expression of six-transmembrane protein of prostate 2 (STAMP2) in macrophages and tried to search for the association between the decreased STAMP2 expression, if any, and carotid atherosclerosis as well as cardiac adaptations. Materials and methods, A total of 97 unrelated Chinese subjects were recruited including 48 subjects with metabolic syndrome (MetS) and 49 controls. Clinical and biochemical characteristics were collected from subjects, with quantification of STAMP2 in monocyte/macrophages. All subjects underwent ultrasonography. Results, STAMP2 expression in macrophages was significantly decreased in MetS as compared with the control group (10·25 ± 9·20 vs. 15·20 ± 9·18, P = 0·009), especially in women patients. Partial correlation analysis showed that STAMP2 expression in macrophages correlated with BMI (r = ,0·375, P = 0·045), age (r = 0·414, P = 0·026) and HDL (r = 0·377, P = 0·044) after controlling for systolic blood pressure (SBP). Furthermore, STAMP2 expression was correlated with PI (r = ,0·454, P = 0·013), LVEF (r = ,0·503, P = 0·005), LA-ESR (r = ,0·424, P = 0·022), LA-S (r = 0·469, P = 0·010) and mitral E/A ratio (r = 0·492, P = 0·005) after controlling for SBP. Still, in multivariable analysis, STAMP2 expression was independently associated with IMTmean, PI and mitral E/A ratio. Conclusions, In MetS patients, especially women patients, STAMP2 expression was down-regulated in peripheral blood mononuclear cell, which was correlated with carotid atherosclerosis and cardiac adaptation. [source]

Metabolic and anti-inflammatory benefits of eccentric endurance exercise , a pilot study

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2008
H. Drexel
ABSTRACT Background, Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown. Materials and methods, We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. Fasting and postprandial metabolic profiles were obtained at baseline and after the two month periods of eccentric and concentric exercise, respectively. Results, Forty-two of the 45 participants completed the study; the compliance rate was therefore 93%. Compared with baseline, eccentric exercise lowered total cholesterol (by 4·1%; P = 0·026), low-density lipoprotein (LDL) cholesterol (by 8·4%, P = 0·001), Apolipoprotein B/Apolipoprotein A1 ratio (by 10·9%, P < 0·001), homeostasis model assessment of insulin resistance scores (by 26·2%, P = 0·017) and C-reactive protein (by 30·0%; P = 0·007); the magnitude of these changes was comparable to that of concentric exercise. Eccentric exercise improved glucose tolerance (by 6·2%, P = 0·023), whereas concentric exercise improved triglyceride tolerance (by 14·9%, P = 0·022). Conclusions, Eccentric endurance exercise is a promising new exercise modality with favourable metabolic and anti-inflammatory effects and is well applicable to sedentary individuals. [source]

Sulfate-reducing bacterial community response to carbon source amendments in contaminated aquifer microcosms

FEMS MICROBIOLOGY ECOLOGY, Issue 1 2002
Jutta Kleikemper
Abstract Microbial sulfate reduction is an important metabolic activity in many reduced habitats. However, little is known about the sulfate-reducing communities inhabiting petroleum hydrocarbon (PHC)-contaminated freshwater aquifer sediments. The purpose of this study was to identify the groups of sulfate-reducing bacteria (SRB) selectively stimulated when sediment from a PHC-contaminated freshwater aquifer was incubated in sulfate-reducing aquifer microcosms that were amended with specific carbon sources (acetate, butyrate, propionate, lactate, and citrate). After 2 months of incubation, the SRB community was characterized using phospholipid fatty acid (PLFA) analysis combined with multivariate statistics as well as fluorescence in situ hybridization (FISH). Molybdate was used to specifically inhibit SRB in separate microcosms to investigate the contribution of non-SRB to carbon source degradation. Results indicated that sulfate reduction in the original sediment was an important process but was limited by the availability of sulfate. Substantially lower amounts of acetate and butyrate were degraded in molybdate treatments as compared to treatments without molybdate, suggesting that SRB were the major bacterial group responsible for carbon source turnover in microcosms. All of the added carbon sources induced changes in the SRB community structure. Members of the genus Desulfobulbus were present but not active in the original sediment but an increase of the fatty acids 15:1,6c and 17:1,6c and FISH results showed an enrichment of these bacteria in microcosms amended with propionate or lactate. The appearance of cy17:0 revealed that bacteria affiliated with the Desulfobacteriaceae were responsible for acetate degradation. Desulfovibrio and Desulfotomaculum spp. were not important populations within the SRB community in microcosms because they did not proliferate on carbon sources usually favored by these organisms. Metabolic, PLFA, and FISH results provided information on the SRB community in a PHC-contaminated freshwater environment, which exhibited stimulation patterns similar to other (e.g. marine) environments. [source]

Effects of augmentation of coarse particulate organic matter on metabolism and nutrient retention in hyporheic sediments

FRESHWATER BIOLOGY, Issue 10 2002
C. L. Crenshaw
SUMMARY 1.,Metabolic and biogeochemical processes in hyporheic zones may depend on inputs of coarse particulate organic matter. Our research focused on how differing quantity and quality of organic matter affects metabolism and nutrient retention in the hyporheic zone of a first-order Appalachian stream. 2.,Sixteen plots were established on a tributary of Hugh White Creek, NC, U.S.A. Sediment was extracted and treated with leaves, wood, plastic strips or remained unamended. Following treatment, sediment was returned to the stream and, approximately 3 months later, samples were removed from each plot. 3.,Aerobic and anaerobic metabolism were measured as the change in O2 and CO2 in recirculating microcosms. At the same time, we monitored other possible terminal electron accepting processes and changes in nutrient concentrations. Aerobic metabolism was low in all treatments and respiratory quotients calculated for all treatments indicated that metabolism was dominated by anaerobic processes. 4.,Rates of anaerobic respiration and total (combined aerobic and anaerobic) respiration were significantly greater (P < 0.05) in plots treated with leaf organic matter compared to controls. 5.,Addition of leaves, which had a low C:N ratio, stimulated respiration in hyporheic sediments. Anaerobic processes dominated metabolism in both control and amended sediments. Enhanced metabolic rates increased retention of many solutes, indicating that energy flow and nutrient dynamics in the subsurface of streams may depend upon the quantity and quality of imported carbon. [source]

Metabolic and luteal function in winter-calving Spanish beef cows as affected by calf management and breed

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2010
J. Álvarez-Rodríguez
Summary This experiment aimed at evaluating the effect of calf management and breed on the metabolic and luteal function of post-partum beef cows fed at maintenance. Fifty multiparous cows, 22 Parda de Montaña (PA) and 28 Pirenaica (PI), were assigned to either suckling once-daily for 30 min (RESTR) or ad libitum (ADLIB) from the day after calving. Blood samples were collected to analyse metabolites [non-esterified fatty acids (NEFA), ,-hydroxybutyrate, total protein and urea)], insulin-like growth factor-I (IGF-I) and progesterone (P4) at different intervals. Cows from RESTR maintained their live-weight (LW) over the first 3 months post-partum, whereas ADLIB cows lost nearly 4% LW. Both genotypes showed similar LW gains during this period (p > 0.10). Calf daily gains were lower in RESTR than in ADLIB treatment (p < 0.05), but similar across breeds (p > 0.10). Milk and lactose production were lower in RESTR cows than in ADLIB (p < 0.05). Milk and protein yield were greater in PA than in PI breed (p < 0.05). Serum NEFA, total protein and urea were higher in PI cows suckling ADLIB than in the rest (p < 0.05). Cows from PI breed had greater NEFA values than PA ones on the first week post-partum (p < 0.001). Circulating IGF-I was not affected by suckling frequency, breed nor their interaction (p > 0.10). Suckling frequency, but not breed, affected the interval from calving to first ovulation (p < 0.001), being shorter in RESTR than in ADLIB cows. In conclusion, the ad libitum suckling practice improved cow milk yield and offspring gain compared to once-daily suckling for 30 min from the day after calving, at the expense of impairing the onset of cyclicity. The effect of calf management was confounded with breed on the studied blood biochemical constituents, but any of these metabolites influenced the role of endocrine IGF-I in these genotypes. [source]

Metabolic and productive response to ruminal protein degradability in early lactation cows fed untreated or xylose-treated soybean meal-based diets

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 6 2009
M. Jahani-Moghadam
Summary Effects of different dietary rumen undegradable (RUP) to degradable (RDP) protein ratios on ruminal nutrient degradation, feed intake, blood metabolites and milk production were determined in early lactation cows. Four multiparous (43 ± 5 days in milk) and four primiparous (40 ± 6 days in milk) tie-stall-housed Holstein cows were used in a duplicated 4 × 4 Latin square design with four 21-day periods. Each period had 14-day of adaptation and 7-day of sampling. Diets contained on a dry matter (DM) basis, 23.3% alfalfa hay, 20% corn silage and 56.7% concentrate. Cows were first offered alfalfa hay at 7:00, 15:00 and 23:00 hours, and 30 min after each alfalfa hay delivery were offered a mixture of corn silage and concentrate. Treatments were diets with RUP:RDP ratios of (i) 5.2:11.6 (control), (ii) 6.1:10.6, (iii) 7.1:9.5 and (iv) 8.1:8.5, on a dietary DM% basis. Different RUP:RDP ratios were obtained by partial and total replacement of untreated soybean meal (SBM) with xylose-treated SBM (XSBM). In situ study using three rumen-cannulated non-lactating cows showed that DM and crude protein (CP) of SBM had greater rapidly degradable fractions. The potentially degradable fractions were degraded more slowly in XSBM. Treatment cows produced greater milk, protein, lactose, solids-non-fat and total solids than control cows. Increasing RUP:RDP reduced blood urea linearly. Feed costs dropped at RUP:RDP ratios of 6.1:10.6 and 7.1:9.5, but not at 8.1:8.5, compared with the 5.2:11.6 ratio. Intake of DM and CP, rumen pH, blood glucose, albumin and total protein, faecal and urine pH, changes in body weight and body condition score, and milk lactose and solids-non-fat percentages did not differ among treatments. Results provide evidence that increasing dietary RUP:RDP ratio from 5.2:11.6 to 7.1:9.5 optimizes nitrogen metabolism and milk production and reduces feed costs in early lactation cows. Reduced blood urea suggests reprodutive benefits. [source]

Adduct-forming tendencies of cationic triarylmethane dyes with proteins: Metabolic and toxicological implications

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2004
Özden Tacal
Abstract The formation of colorless adducts by four cationic triarylmethane dyes (TAM+s), methyl green (MeG+), malachite green (MG+), pararosaniline (PR+), and crystal violet (CV+) was studied spectrophotometrically at 25°C, in 50 mM 3-(N-morpholino)propanesulfonic acid (MOPS) buffer (pH 8), by monitoring the loss in TAM+ color in the absence and presence of human serum proteins as potential addends. Unfractionated serum caused a rapid bleaching of MeG+ and MG+, while PR+ and CV+ were unaffected. Sephacryl S200 HR chromatographic screening of the serum revealed two composite peaks of MeG+ -bleaching activity. The major peak (Mr range, 40,000,130,000) overlapped with and extended on either side of the albumin peak. The minor peak corresponding to ca. 10% of the total MeG+ -bleaching capacity had Mr > 230,000. MG+ -bleaching activity dominated the entire chromatographic profile and implicated a multitude of minority proteins with a high capacity to form colorless MG adducts. It is concluded that highly electrophilic TAM+s such as MeG+ and MG+ must be quantitatively trapped in the form of dye,protein adducts in biological fluids and that the primary in vivo effects (e.g. toxicity) of such dyes most likely arise from ligand-type effects on multiple protein targets. Mechanisms that call for unmodified TAM+ structure (radical-mediated redox changes, DNA intercalation) may be more relevant to the in vivo impact of dyes such as PR+ and CV+ that have a lower tendency to form adducts. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:253,256, 2004 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20034 [source]

Twenty-Four Hours Postoperative Results After Orthotopic Cardiac Transplantation in Swine

JOURNAL OF CARDIAC SURGERY, Issue 4 2007
Matthias Siepe M.D.
However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation.Materials and Methods: Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. Results: The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. Conclusions: For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated. [source]

Chronic Intermittent Injections of High-Dose Ethanol During Adolescence Produce Metabolic, Hypnotic, and Cognitive Tolerance in Rats

ALCOHOLISM, Issue 10 2003
Janelle M. Silvers
Background: Many humans are first exposed to ethanol during adolescence, the time at which they are most likely to binge drink ethanol. Chronic intermittent ethanol (CIE) exposure produces ethanol tolerance in adolescent rodents. Recent studies suggested that adolescent animals administered CIE experienced increased cognitive impairment following an ethanol challenge. These studies further explore development of ethanol tolerance caused by CIE in adolescence, and whether CIE during adolescence leads to altered ethanol response in adulthood. Methods: Beginning postnatal day (P) 30, adolescent rats were administered 5.0 g/kg ethanol or saline every 48 hours for 20 days. In experiment I, animals were tested for differential weight gain. In experiment II, loss of righting reflex (LORR) was observed after each injection, then at completion of pretreatment all animals were tested with 5.0 g/kg ethanol and LORR was observed. In experiment III, blood ethanol levels were observed and elimination rates calculated after the first and fifth pretreatments. All animals were tested with 5.0 g/kg at completion of pretreatment and elimination rates were recalculated. In experiment IV, animals were trained on the spatial version of the Morris Water Maze Task (MWMT) on non-treatment days. Following completion of pretreatment and training, animals were tested after receiving an ethanol (1.0, 1.5, or 2.0 g/kg), or saline. Tests for experiments II, III, and IV were repeated in the same animals following 12 ethanol-free days. Results: Chronic intermittent ethanol exposure during adolescence caused differential weight gain (experiment I). Adolescent rats developed tolerance to ethanol-induced LORR (experiment II) and metabolic tolerance to ethanol (experiment III). This tolerance was seen after 12 ethanol-free days. CIE also attenuated ethanol-induced spatial memory deficits in the MWMT (experiment IV). This effect was not long-lasting. Conclusions: Following CIE pretreatment during adolescence, tolerance developed to the hypnotic and cognitive impairing effects of ethanol, along with increased metabolic rate and decreased weight gain. These results further emphasize the ability of CIE to produce a variety of effects during adolescence, some having long-lasting consequences. [source]

Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009
V. W.-S.
Summary Background, Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear. Aim, To evaluate the metabolic and histological features of NAFLD patients with different ALT levels. Methods, A total of 173 consecutive patients with biopsy-proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared. Results, Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within-patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis. Discussion, Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non-alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level. [source]

The repeatability of submaximal endurance exercise testing in cystic fibrosis,

PEDIATRIC PULMONOLOGY, Issue 1 2007
MB BCh BAO, Sinead C. Barry BSc
Abstract Submaximal endurance cycle ergometer exercise tests are used to measure the efficacy of an exercise intervention, but the repeatability of these tests in patients with cystic fibrosis (CF) has not been established. The purpose of this study was to examine the repeatability of submaximal endurance testing in stable CF. Fifteen adults with CF underwent two submaximal endurance tests carried out over a 7-day period. A subset of six subjects returned 28 days later for a third submaximal endurance test. Workload was set at 80% of maximum workload and exercise was performed to exhaustion. Oxygen consumption, minute ventilation, tidal volume, carbon dioxide output, respiratory rate, heart rate, and oxygen saturation were measured at rest, at end exercise and at four matched times during the submaximal endurance tests (20, 40, 60, and 80% of exercise duration calculated from the first endurance test). Submaximal endurance test time was highly repeatable with no significant learning effect identified on multiple testing. Submaximal endurance exercise time demonstrated a variability of 5.7% which is consistent with high levels of repeatability. Metabolic, ventilatory and cardiac variables were all also highly reproducible between test days. Submaximal endurance testing is repeatable in stable CF, confirming that submaximal endurance tests are a reliable tool for assessment of therapeutic benefit in patients with CF. Pediatr Pulmonol. 2007; 42:75,82. © 2006 Wiley-Liss, Inc. [source]

Crayfish Procambarus clarkii Retina and Nervous System Exhibit Antioxidant Circadian Rhythms Coupled with Metabolic and Luminous Daily Cycles

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2009
María Luisa Fanjul-Moles
Based on previous work in which we proposed midgut as a putative peripheral oscillator responsible for circadian reduced glutathione (GSH) crayfish status, herein we investigated the retina and optic lobe-brain (OL-B) circadian GSH system and its ability to deal with reactive oxygen species (ROS) produced as a consequence of metabolic rhythms and light variations. We characterized daily and antioxidant circadian variations of the different parameters of the glutathione system, including GSH, oxidized glutathione (GSSG), glutathione reductase (GR) and glutathione peroxidase (GPx), as well as metabolic and lipoperoxidative circadian oscillations in retina and OL-B, determining internal and external GSH-system synchrony. The results demonstrate statistically significant bi- and unimodal daily and circadian rhythms in all GSH-cycle parameters, substrates and enzymes in OL-B and retina, as well as an apparent direct effect of light on these rhythms, especially in the retina. The luminous condition appears to stimulate the GSH system to antagonize ROS and lipid peroxidation (LPO) daily and circadian rhythms occurring in both structures, oscillating with higher LPO under dark conditions. We suggest that the difference in the effect of light on GSH rhythmic mechanisms of both structures for antagonizing ROS could be due to differences in glutathione-system coupling strength with the circadian clock. [source]

Ferrocenyl Quinone Methides as Strong Antiproliferative Agents: Formation by Metabolic and Chemical Oxidation of Ferrocenyl Phenols,

ANGEWANDTE CHEMIE, Issue 48 2009
Didier Hamels
Schwer verdaulich für Krebszellen: Potenziell zytotoxische Ferrocenylchinonmethide entstehen durch metabolische oder chemische Oxidation von Ferrocenylphenolen. Die Spezies wirken stark proliferationshemmend. [source]

Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: A randomized clinical study

ANZ JOURNAL OF SURGERY, Issue 8 2001
Susan J. Neuhaus
Background: Previous studies using animal models have demonstrated that carbon dioxide (CO2) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO2 insufflation on intraperitoneal markers of immunological and metabolic function. Methods: Eighteen patients undergoing elective upper gastrointestinal laparoscopic surgery were randomized to have insufflation achieved by using either helium (n = 8) or CO2 (n = 10) gas. Intraperitoneal pH was monitored continuously during surgery, and peritoneal macrophage function was determined by harvesting peritoneal macrophages at 5 min and 30 min after commencing laparoscopy, and then assessing their ability to produce tumour necrosis factor-, (TNF-,), and their phagocytic function. Results: Carbon dioxide laparoscopy was associated with a lower intraperitoneal pH at the commencement of laparoscopy, although this difference disappeared as surgery progressed. The production of TNF-, was better preserved by CO2 laparoscopy, but the insufflation gas used did not affect macrophage phagocytosis. Patients undergoing helium laparoscopy required less postoperative analgesia. Conclusion: The choice of insufflation gas can affect intraperitoneal macrophage function in the clinical setting, and possibly acid,base balance. The present study suggested no immunological advantages for the clinical use of helium as an insufflation gas. The outcomes of the present study, however, are different to those obtained from previous laboratory studies and further research is needed to confirm this outcome. [source]

Cardiorespiratory, Metabolic, and Biomechanical Responses During Functional Electrical Stimulation Leg Exercise: Health and Fitness Benefits

ARTIFICIAL ORGANS, Issue 4 2009
Fahad Aziz MD
No abstract is available for this article. [source]

Metabolic and transcriptional response of recombinant Escherichia coli to elevated dissolved carbon dioxide concentrations

BIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009
Antonino Baez
Abstract The effect of dissolved carbon dioxide (dCO2) concentration on the stoichiometric and kinetic constants and by-product accumulation was determined for Escherichia coli cells producing recombinant green fluorescent protein (GFP). Constant dCO2, in the range of 20,300,mbar, was maintained during batch cultures by manipulating the inlet gas composition. As dCO2 increased, specific growth rate (µ) decreased, and acetate accumulation and the time for onset of GFP production increased. Maximum biomass yield on glucose and GFP concentration were affected for dCO2 above 70 and 150,mbar, respectively. Expression analysis of 16 representative genes showed that E. coli can respond at the transcriptional level upon exposure to increasing dCO2, and revealed possible mechanisms responsible for the detrimental effects of high dCO2. Genes studied included those involved in decarboxylation reactions (aceF, icdA, lpdA, sucA, sucB), genes from pathways of production and consumption of acetate (ackA, poxB, acs, aceA, fadR), genes from gluconeogenic and anaplerotic metabolism (pckA, ppc), genes from the acid resistance (AR) systems (adiA, gadA, gadC), and the heterologous gene (gfp). The transcription levels of tricarboxylic acid (TCA) cycle genes (icdA, sucA, sucB) and glyoxylate shunt (aceA) decreased as dCO2 increased, whereas fadR (that codes for a negative regulator of the glyoxylate operon) and poxB (that codes for PoxB which is involved in acetate production from pyruvate) were up-regulated as dCO2 increased up to 150,mbar. Furthermore, transcription levels of genes from the AR systems increased as dCO2 increased up to 150,mbar, indicating that elevated dCO2 triggers an acid stress response in E. coli cells. Altogether, such results suggest that the increased acetate accumulation and reduction in µ, biomass yield and maximum GFP concentration under high dCO2 resulted from a lower carbon flux to TCA cycle, the concomitant accumulation of acetyl-CoA or pyruvate, and the acidification of the cytoplasm. Biotechnol. Bioeng. 2009; 104: 102,110 © 2009 Wiley Periodicals, Inc. [source]

New Fatty Acid Oxidation Inhibitors with Increased Potency Lacking Adverse Metabolic and Electrophysiological Properties.

CHEMINFORM, Issue 16 2004
Dmitry O. Koltun
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

Metabolic and cardiopulmonary effects of detraining after a structured exercise training programme in young PCOS women

CLINICAL ENDOCRINOLOGY, Issue 6 2008
Francesco Orio
Summary Objective The aim of the present study was to determine if the favourable cardiopulmonary and metabolic benefits induced by exercise training (ET) programme are maintained after its cessation. Patients Thirty-two young overweight polycystic ovary syndrome (PCOS) women matched for age and body mass index (BMI) with other 32 PCOS patients was enrolled. The first group [PCOS-T (trained)] underwent 24-week ET programme, whereas the second [PCOS-DT (detrained)] underwent 12-week ET programme followed by 12-week detraining period. Methods At baseline, after 12- and 24-week follow-up, all PCOS women were studied for their hormonal (ovarian and adrenal androgens), metabolic (glucose and insulin) and lipid profile, and underwent cardiopulmonary exercise test. Results After the initial 12-week ET programme, both PCOS-T and PCOS-DT groups, without differences between groups, showed a similar significant (P < 0·05) improvement in BMI, fasting insulin, areas under curve insulin (AUCINS), glucose and insulin AUC (AUCGLU/INS), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and maximal oxygen consumption at cardiopulmonary exercise test (VO2max). At 24-week follow-up, PCOS-T group showed a significant (P < 0·05) improvement in BMI, fasting insulin, AUCINS, AUCGLU/INS, LDL-C, HDL-C and VO2max, in comparison to baseline and 12-week follow-up. At same follow-up visit, the all parameters resulted significantly (P < 0·05) worsened in PCOS-DT group in comparison to 12-week follow-up and PCOS-T group. In PCOS-DT group, no parameter assessed at 24-week follow-up was significantly different in comparison with baseline. Conclusion In young PCOS women, 12-week detraining resulted in a complete loss of the favourable adaptations obtained after ET. [source]

Impaired cardiac functional reserve in type 2 diabetic db/db mice is associated with metabolic, but not structural, remodelling

ACTA PHYSIOLOGICA, Issue 1 2010
A. Daniels
Abstract Aim:, To identify the initial alterations in myocardial tissue associated with the early signs of diabetic cardiac haemodynamic dysfunction, we monitored changes in cardiac function, structural remodelling and gene expression in hearts of type 2 diabetic db/db mice. Methods:, Cardiac dimensions and function were determined echocardiographically at 8, 12, 16 and 18 weeks of age. Left ventricular pressure characteristics were measured at 18 weeks under baseline conditions and upon dobutamine infusion. Results:, The db/db mice were severely diabetic already at 8 weeks after birth, showing elevated fasting blood glucose levels and albuminuria. Nevertheless, echocardiography revealed no significant changes in cardiac function up to 18 weeks of age. At 18 weeks of age, left ventricular pressure characteristics were not significantly different at baseline between diabetic and control mice. However, dobutamine stress test revealed significantly attenuated cardiac inotropic and lusitropic responses in db/db mice. Post-mortem cardiac tissue analyses showed minor structural remodelling and no significant changes in gene expression levels of the sarcoplasmic reticulum calcium ATPase (SERCA2a) or ,1-adrenoceptor (,1-AR). Moreover, the phosphorylation state of known contractile protein targets of protein kinase A (PKA) was not altered, indicating unaffected cardiac ,-adrenergic signalling activity in diabetic animals. By contrast, the substantially increased expression of uncoupling protein-3 (UCP3) and angiopoietin-like-4 (Angptl4), along with decreased phosphorylation of AMP-activated protein kinase (AMPK) in the diabetic heart, is indicative of marked changes in cardiac metabolism. Conclusion:, db/db mice show impaired cardiac functional reserve capacity during maximal ,-adrenergic stimulation which is associated with unfavourable changes in cardiac energy metabolism. [source]

Diabetic embryopathy: Studies using a rat embryo culture system and an animal model

CONGENITAL ANOMALIES, Issue 3 2005
Shoichi Akazawa
ABSTRACT The mechanism of diabetic embryopathy was investigated using in vitro experiments in a rat embryo culture system and in streptozotocin-induced diabetic pregnant rats. The energy metabolism in embryos during early organogenesis was characterized by a high rate of glucose utilization and lactic acid production (anaerobic glycolysis). Embryos uninterruptedly underwent glycolysis. When embryos were cultured with hypoglycemic serum, such embryos showed malformations in association with a significant reduction in glycolysis. In a diabetic environment, hyperglycemia caused an increased glucose flux into embryonic cells without a down-regulation of GLUT1 and an increased metabolic overload on mitochondria, leading to an increased formation of reactive oxygen species (ROS). Activation of the hexamine pathway, subsequently occurring with increased protein carbonylation and increased lipid peroxidation, also contributed to the increased generation of ROS. Hyperglycemia also caused a myo-inositol deficiency with a competitive inhibition of ambient glucose, which might have been associated with a diminished phosphoinositide signal transduction. In the presence of low activity of the mitochondrial oxidative glucose metabolism, the ROS scavenging system in the embryo was not sufficiently developed. Diabetes further weakened the antioxidant system, especially, the enzyme for GSH synthesis, ,-GCS, thereby reducing the GSH concentration. GSH depletion also disturbed prostaglandin biosynthesis. An increased formation of ROS in a diminished GSH-dependent antioxidant system may, therefore, play an important role in the development of embryonic malformations in diabetes. [source]

Impaired contractile function and mitochondrial respiratory capacity in response to oxygen deprivation in a rat model of pre-diabetes

ACTA PHYSIOLOGICA, Issue 4 2009
M. F. Essop
Abstract Aim:, Obesity is a major contributor to the global burden of disease and is closely associated with the development of type 2 diabetes and cardiovascular diseases. This study tested the hypothesis that mitochondrial respiratory capacity of the pre-diabetic heart is decreased leading to impaired contractile function and tolerance to ischaemia/reperfusion. Methods:, Eight-week-old male Wistar rats were fed a high caloric diet for 16 weeks after which anthropometric, metabolic, cardiac and mitochondrial parameters were evaluated vs. age-matched lean controls. Cardiac function (working heart perfusions) and mitochondrial respiratory capacity were assessed at baseline and in response to acute oxygen deprivation. Results:, Rats fed the high caloric diet exhibited increased body weight and visceral fat vs. the control group. Heart weights of obese rats were also increased. Triglyceride, fasting plasma insulin and free fatty acid levels were elevated, while high-density lipoprotein cholesterol levels were reduced in the obese group. Contractile function was attenuated at baseline and further decreased after subjecting hearts to ischaemia-reperfusion. Myocardial infarct sizes were increased while ADP phosphorylation rates were diminished in obese rats. However, no differences were found for mtDNA levels and the degree of oxidative stress-induced damage. Conclusions:, These data show that decreased mitochondrial bioenergetic capacity in pre-diabetic rat hearts may impair respiratory capacity and reduce basal contractile function and tolerance to acute oxygen deprivation. [source]

AMPK activators , potential therapeutics for metabolic and other diseases

ACTA PHYSIOLOGICA, Issue 1 2009
G. Zhou
Abstract AMP-activated protein kinase (AMPK)-mediated cellular metabolic responses to tissue-specific and whole-body stimuli play a vital role in the control of energy homeostasis. As a cellular energy-sensing mechanism, AMPK activation stimulates glucose uptake and fat oxidation, while it suppresses lipogenesis and gluconeogenesis. The cumulative effects of AMPK activation lead to beneficial metabolic states in liver, muscle and other peripheral tissues that are critical in the pathogenesis of obesity, type 2 diabetes and related metabolic disorders. Activators of AMPK that target selected tissues hold potential as novel therapeutics for diseases in which altered energy metabolism contributes to aetiology. [source]

Bioenergetics and the epigenome: Interface between the environment and genes in common diseases

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2010
Douglas C. Wallace
Abstract Extensive efforts have been directed at using genome-wide association studies (GWAS) to identify the genes responsible for common metabolic and degenerative diseases, cancer, and aging, but with limited success. While environmental factors have been evoked to explain this conundrum, the nature of these environmental factors remains unexplained. The availability of and demands for energy constitute one of the most important aspects of the environment. The flow of energy through the cell is primarily mediated by the mitochondrion, which oxidizes reducing equivalents from hydrocarbons via acetyl-CoA, NADH + H+, and FADH2 to generate ATP through oxidative phosphorylation (OXPHOS). The mitochondrial genome encompasses hundreds of nuclear DNA (nDNA)-encoded genes plus 37 mitochondrial DNA (mtDNA)-encoded genes. Although the mtDNA has a high mutation rate, only milder, potentially adaptive mutations are introduced into the population through female oocytes. In contrast, nDNA-encoded bioenergetic genes have a low mutation rate. However, their expression is modulated by histone phosphorylation and acetylation using mitochondrially-generated ATP and acetyl-CoA, which permits increased gene expression, growth, and reproduction when calories are abundant. Phosphorylation, acetylaton, and cellular redox state also regulate most signal transduction pathways and activities of multiple transcription factors. Thus, mtDNA mutations provide heritable and stable adaptation to regional differences while mitochondrially-mediated changes in the epigenome permit reversible modulation of gene expression in response to fluctuations in the energy environment. The most common genomic changes that interface with the environment and cause complex disease must, therefore, be mitochondrial and epigenomic in origin. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:114,119. [source]

Activity-based restorative therapies: Concepts and applications in spinal cord injury-related neurorehabilitation

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2009
Cristina L. Sadowsky
Abstract Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to CNS plasticity, repair, and regeneration, all related to persistently maintaining appropriate levels of neurological activity both below and above the area where the damage occurred. It is now possible to envision functional repair of the nervous system by implementing rehabilitative interventions. Making the transition from "bench to bedside" requires careful analysis of existing basic science evidence, strategic focus of clinical research, and pragmatic implementation of new therapeutic tools. Activity, defined as both function specific motor task and exercise appears to be a necessity for optimization of functional, metabolic, and neurological status in chronic paralysis. Crafting a comprehensive rehabilitative intervention focused on functional improvement through neurological gains seems logical. The terms activity-based restorative therapies, activity-based therapies, and activity-based rehabilitation have been coined in the last 10 years to describe a new fundamental approach to deficits induced by neurological paralysis. The goal of this approach is to achieve activation of the neurological levels located both above and below the injury level using rehabilitation therapies. This article reviews basic and clinical science evidence pertaining to implementation of physical activity and exercise as a therapeutic tool in the management of chronic spinal cord-related neurological paralysis. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:112,116. [source]