The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5.

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases.

Involvement of caspase-8 in chemotherapy-induced apoptosis of patient derived leukemia cell lines independent of the death receptor pathway and downstream from mitochondria.

Resistance of leukemic cells to chemotherapy frequently occurs in patients with acute leukemia, which may be caused by alterations in common apoptotic pathways. Controversy exists whether cytostatic agents induce the mitochondrial or death receptor pathway of apoptosis. In the mitochondrial pathway cytochrome C release and caspase-9 activation play a central role in the induction of apoptosis, while formation of a Death Inducing Signaling Complex (DISC) and caspase-8 activation have been reported to be essential in death receptor-induced apoptosis. Here, we show in human derived myeloid and lymphoblastic leukemia cell lines that caspase-8 plays a more important role than previously expected in apoptosis mediated via the mitochondrial pathway. We demonstrated in these malignant cells chemotherapy-induced apoptosis independent of the death receptor pathway, since blocking this pathway using a retroviral construct encoding Flice inhibitory protein (FLIP) did not inhibit drug-induced apoptosis or caspase-8 activation, while overexpression of Bcl-2 completely inhibited both events. Furthermore, we showed that activation of caspase-8 by cytostatic agents occurred downstream from mitochondria. Since caspase-8 plays a central role in both death receptor- and chemotherapy-induced apoptosis of malignant cells from patients with acute leukemia, therapeutic strategies focusing at modulation and activation of caspase-8 may be successful in the treatment of drug-resistant malignancies.

Vapour transfer in two-layer clothing due to diffusion and ventilation.

An experiment was carried out to measure the vapour resistance of two-layer clothing ensembles as a function of air permeability of the outer layer, open or closed apertures, wind, and walking, both for the total ensemble and for the outer garment alone. Six subjects walked on a treadmill (0.0, 2.5, and 5 km.h-1) which was placed in a wind tunnel (0.2, 0.7, and 3.0 m.s-1). They wore long underwear and an outer garment made of impermeable (imp), microporous (mpo), low air permeable (loa), or high air permeable (hia) fabric. Vapour resistances were determined by a trace gas method, calibrated against water vapour resistance. The vapour resistances of the underclothing and the outer garment were calculated from the measured data, as was the ventilation through the apertures. The vapour resistance of the underclothing was almost constant at 5 mm air equivalent. The ventilation was strongly dependent on wind and motion but still so low (54 l.min-1) that only the impermeable garment could benefit from it noticeably. The vapour resistance of the garments also varied strongly (imp 55-200 mm, mpo 12-20 mm, loa and hia 1-14 mm air equivalent). For the imp garment, this is due to leakage of air, whereas the vapour permeable garments were dominated by the diffusion and air penetration through the fabric. It is concluded that ventilation with vents cannot match the effect of vapour permeability, and that real low vapour resistances are only possible with air permeable fabrics.

Physiological strain due to load carrying in heavy footwear.

To determine the effects of wearing heavy footwear on physiological responses five male and five female subjects were measured while walking on a treadmill (4, 5.25, and 6.5 km.h-1) with different external loads (barefooted, combat boots, and waist pack). While walking without an external load the oxygen uptake, as a percentage of maximal oxygen uptake (%VO2max) of the men increased from 25% VO2max at 4 km.h-1 to 31% VO2max at 5.25 km.h-1 and to 42% VO2max at 6.5 km.h-1. The women had a significantly higher oxygen uptake of 30%, 40%, and 55% VO2max, respectively. In the most strenuous condition, walking at 6.5 km.h-1 with combat boots and waist pack (12 kg), the oxygen uptake for the men and women amounted to 53% and 75% VO2max, respectively. The heart rate showed a similar response to the oxygen uptake, the women having a heart rate which was 15-40 beats.min-1 higher than that of the men, depending on the experimental condition. The perceived exertion was shown to be greatly dependent on the oxygen uptake. From the results a regression formula was calculated predicting the oxygen uptake depending on the mass of the footwear, walking speed and body mass. It was concluded that the mass of footwear resulted in an increase in the energy expenditure which was a factor 1.9-4.7 times greater than that of a kilogram of body mass, depending on sex and walking speed.