Defining the cost of the Egyptian lymphatic filariasis elimination programme

BACKGROUND: Ultrasonography (USG) is known to be a suitable tool for diagnosis in lymphatic filariasis as the adult filarial nematode Wuchereria bancrofti in scrotal lymphatic vessels of infected men can be detected by the characteristic pattern of movement, the Filaria Dance Sign. In onchocerciasis, moving adult worms have not yet been demonstrated by USG. In addition the verification of drug effects on living adult Onchocerca volvulus filariae in trials is hampered by the lack of tools for longitudinal observation of alterations induced by potentially macrofilaricidal drugs in vivo. The present study was carried out to determine the frequency of detection of moving adult filariae of O. volvulus by USG. METHODS: In an endemic region for onchocerciasis in Ghana, 61 patients infected with onchocerciasis were recruited by palpation and onchocercomas examined by USG using an ultrasound system equipped with a 7.5 - 10 MHz linear transducer. Onchocercomas were recorded on videotape and evaluated with regard to location, number and size, as well as to movements of adult filariae. RESULTS: In the 61 patients 303 onchocercomas were found by palpation and 401 onchocercomas were detected by USG. In 18 out of 61 patients (29.5%), altogether 22 nodules with moving adult O. volvulus filariae were detected and are presented in animated ultrasound images as mp-4 videos. CONCLUSION: Ultrasonographical examinations of onchocercomas where living adult filariae can be displayed may serve as a new tool for the longitudinal observation in vivo of patients with onchocerciasis undergoing treatment and as an adjunct to histological evaluation.     

Hypoxic stress in diabetic pregnancy contributes to impaired embryo gene expression and defective development by inducing oxidative stress

We have shown that neural tube defects (NTD) in a mouse model of diabetic embryopathy are associated with deficient expression of Pax3, a gene required for neural tube closure. Hyperglycemia-induced oxidative stress is responsible. Before organogenesis, the avascular embryo is physiologically hypoxic (2-5% O(2)). Here we hypothesized that, because O(2) delivery is limited at this stage of development, excess glucose metabolism could accelerate the rate of O(2) consumption, thereby exacerbating the hypoxic state. Because hypoxia can increase mitochondrial superoxide production, excessive hypoxia may contribute to oxidative stress. To test this, we assayed O(2) flux, an indicator of O(2) availability, in embryos of glucose-injected hyperglycemic or saline-injected mice. O(2) flux was reduced by 30% in embryos of hyperglycemic mice. To test whether hypoxia replicates, and hyperoxia suppresses, the effects of maternal hyperglycemia, pregnant mice were housed in controlled O(2) chambers on embryonic day 7.5. Housing pregnant mice in 12% O(2), or induction of maternal hyperglycemia (>250 mg/dl), decreased Pax3 expression fivefold, and increased NTD eightfold. Conversely, housing pregnant diabetic mice in 30% O(2) significantly suppressed the effect of maternal diabetes to increase NTD. These effects of hypoxia appear to be the result of increased production of mitochondrial superoxide, as indicated by assay of lipid peroxidation, reduced glutathione, and H(2)O(2). Further support of this interpretation was the effect of antioxidants, which blocked the effects of maternal hypoxia, as well as hyperglycemia, on Pax3 expression and NTD. These observations suggest that maternal hyperglycemia depletes O(2) in the embryo and that this contributes to oxidative stress and the adverse effects of maternal hyperglycemia on embryo development.     

Evidence for an early evolutionary emergence of γ-type carbonic anhydrases as components of mitochondrial respiratory complex I

Background  

The complexity of mitochondrial complex I (CI; NADH:ubiquinone oxidoreductase) has increased considerably relative to the homologous complex in bacteria. Comparative analyses of CI composition in animals, fungi and land plants/green algae suggest that novel components of mitochondrial CI include a set of 18 proteins common to all eukaryotes and a variable number of lineage-specific subunits. In plants and green algae, several purportedly plant-specific proteins homologous to γ-type carbonic anhydrases (γCA) have been identified as components of CI. However, relatively little is known about CI composition in the unicellular protists, the characterizations of which are essential to our understanding of CI evolution.     

Establishment of new mouse embryonic stem cell lines is improved by physiological glucose and oxygen

Embryonic stem cell lines are routinely selected and cultured in glucose and oxygen concentrations that are well above those of the intrauterine environment. Supraphysiological glucose and hyperoxia each increase oxidative stress, which could be detrimental to survival in vitro by inhibiting proliferation and/or inducing cell death. The aim of this study was to test whether isolation of new embryonic stem cell lines from murine blastocysts is improved by culture in physiological (5%) oxygen instead of approximately 20%, the concentration of oxygen in room air, or in media containing physiological (100 mg/dL) instead of 450 mg/dL glucose. We found that culturing in either physiological oxygen or physiological glucose improved the success of establishing new murine embryonic stem cell lines, and that culture when concentrations of both oxygen and glucose were physiological improved the success of establishing new lines more than culture in either alone. Physiological oxygen and glucose reduce oxidative stress, as determined by 2',7'-dichloro-dihydrofluorescein fluorescence. BrdU incorporation suggests that physiological oxygen and glucose increase the pool of proliferating cells. Cells isolated in physiological oxygen and glucose are capable of self-renewal and differentiation into all three germ layers in vitro. However, none of the culture conditions prevents cytogenetic instability with prolonged passage. These results suggest that culture of cells derived from murine blastocysts in physiological oxygen and glucose reduces oxidant stress, which increases the success of establishing new embryonic stem cell lines.