Variability in dust exposure in a cement factory in Tanzania

Dust exposure levels were studied in a cement factory in Dar es Salaam, Tanzania, as part of an epidemiological study assessing chronic respiratory health effects. One hundred and twenty personal 'total' dust samples were collected from 80 randomly selected workers from eight a priori occupational groups (OGs) based on work areas using a 37 mm Millipore sampler. The between-group, within-group and within-worker variances were determined to assess the contrast in exposure level between the OGs and to estimate the attenuation and standard error of the theoretical exposure-response slope. Using mixed-effect model estimates, the probability of overexposure relative to the occupational exposure limit (OEL) was assessed for each OG. The geometric means of total dust exposure were higher in the cranes (38.64 mg m(-3)), packing (21.30 mg m(-3)) and crusher (13.48 mg m(-3)) than in the cement mill (3.23 mg m(-3)), kiln (2.87 mg m(-3)), raw mill (1.85 mg m(-3)), maintenance (1.16 mg m(-3)) and administration (0.29 mg m(-3)). The a priori grouping scheme seems to be an efficient scheme because of the high contrast in exposure level between the OGs (0.78) and minimal attenuation of the theoretical exposure-response slope (1.0%). When using the reduced mixed-effect model, the probabilities of overexposure () relative to the OEL of 10 mg m(-3) for total cement dust were higher in the crane (96%), packing (88%) and crusher (73%) than in the cement mill (16%), kiln (14%), raw mill (5%), maintenance (2%) and administration (0.01%).     

Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation

Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-alpha (TNF-alpha) concentrations have been implicated in the development of insulin resistance, but direct evidence in humans is lacking. Here, we demonstrate that TNF-alpha infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method. TNF-alpha directly impairs glucose uptake and metabolism by altering insulin signal transduction. TNF-alpha infusion increases phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, and c-Jun NH(2)-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1. These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake. Thus, excessive concentrations of TNF-alpha negatively regulate insulin signaling and whole-body glucose uptake in humans. Our results provide a molecular link between low-grade systemic inflammation and the metabolic syndrome.     

Genetic background determines the size and structure of the endocrine pancreas

Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred mice were included in the study. For all parameters investigated, there was a pronounced interstrain variation. ANCOVA showed that only mouse strain was statistically significant as an explanatory parameter for the number of islets. Mouse strain, body weight, and pancreas mass reached statistical significance as explanatory parameters for the islet mass, with mouse strain as the most significant predictor. These data show that genetic background is the most important predictor of both the number of islets and total islet volume. We also conclude that inbred mice could be a valuable resource to identify the genes responsible for the size and structure of the endocrine pancreas.     

Intramuscular triacylglycerol in energy metabolism during exercise in humans

Intramuscular triacylglycerol (IMTG) represents an energy store that can be used during exercise, when it may contribute up to 20% of total energy turnover depending on diet, gender, and exercise type. It is important to consider how measurements of IMTG have been performed. Hormone-sensitive lipase is thought to regulate breakdown of IMTG during exercise.     

Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets

Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O2 compared with 21% O2. Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p=0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O(2) (p=0.003) and 100% O2 (p=0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O2 as compared with 21% O2 (p < 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O2 were considerably reduced compared with both baseline (p=0.001) and piglets that were resuscitated with 21% O2 (p=0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Our findings suggest that resuscitation of asphyxiated piglets with 100% O2 is detrimental to the piglet brain compared with resuscitation with 21% O2.     

Immuno-endocrine and metabolic responses to long distance ski racing in world-class male and female cross-country skiers

The purpose of this study was to characterize the extent of immune, endocrine, substrate and metabolic changes during a long-distance cross-country ski race in extremely well-trained athletes and evaluate if the blood perturbations would indicate signs of health risk. Ten male (M) and six female (F) national team skiers were investigated as they followed their usual routines of race preparations. Blood samples were drawn before and immediately after a World Cup 50-km M and 30-km F ski race with a mean finish time of 142 and 104 min, respectively. Hemoglobin, electrolytes, and C-reactive protein remained unchanged for both M and F. Serum testosterone remained unchanged in M, but doubled in F. Significant increases were observed in concentrations of granulocytes (F: 5 x, M: 5 x), natural killer cells (F: 2 x, M: 1.5 x), adrenaline (F: 12 x, M:10 x), noradrenaline (F: 7 x, M:5 x), growth hormone (F: 30 x, M: 2 x), cortisol (F: 1.5 x, M:2 x), glucose (F: 2 x, M:1.5 x), creatine kinase (F: 2 x, M:2 x), uric acid (F: 1.5 x, M: 1.5 x) and non-organic phosphate (F:2 x, M:2 x), while insulin concentration decreased (F: 0.5x, M: 0.8 x). Free fatty acid (FFA) concentration increased (F:2 x, M: 3 x). In conclusion, we observed substantial changes in several immuno-endocrine, substrate and metabolic measurements after long distance cross-country ski racing and suggest that some of these marked changes may reflect the large amount of muscle mass involved during skiing.     

Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction

The mechanisms that mediate the tightly controlled production and clearance of glucose during muscular work are unclear, and it has been suggested that an unidentified "work factor" exists that influences the contraction-induced increase in endogenous glucose production (EGP). The cytokine interleukin (IL)-6 is released from skeletal muscle during contraction. Here we show that IL-6 contributes to the contraction-induced increase in EGP. Six men performed 2 h of bicycle exercise on three separate occasions, at a relatively high intensity (HI) or at a low intensity with (LO + IL-6) or without (LO) an infusion of recombinant human IL-6 that matched the circulating concentration of IL-6 seen in HI exercise. The stable isotope 6,6 (2)H(2) glucose was infused to calculate EGP (rate of glucose appearance [R(a)]), whole-body glucose disposal (rate of glucose disappearance [R(d)]), and metabolic clearance rate (MCR) of glucose. Glucose R(a), R(d), and MCR were higher (P < 0.05) at HI than at LO. Throughout exercise at LO + IL-6, glucose R(a) and R(d) were higher (P < 0.05) than LO, even though the exercise intensity was identical. In addition, MCR was higher (P < 0.05) at LO + IL-6 than at LO at 90 min. Insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone were identical when comparing LO + IL-6 with LO. These data suggest that IL-6 influences glucose homeostasis during exercise. Our results provide potential new insights into factors that mediate glucose production and disposal and implicates IL-6 in the so-called "work factor."