Evaluation of transgenic approaches for controlling tuber moth in potatoes.

A wide spectrum of strategies to genetically engineer potato plants resistant to potato tuber moth, Phthorimaea operculella (Zeller), have been investigated. The potato cv Iwa was transformed with a range of genes under the transcriptional control of the CaMV 35S promoter using Agrobacterium-mediated gene transfer. The transferred genes encode protease inhibitors (spleen inhibitor and alpha1-antitrypsin inhibitor), biotin-binding proteins (avidin and streptavidin) and Cry proteins (crylAc9, cry1Ba1, crylCa5 and cry9Aa2). Of these three transgenic approaches, cry genes have proved the most useful. In order to control the expression of the cry genes in foliage and not in the tubers a light-inducible Lhca3 promoter from potato was also used. The interaction of different cry genes was investigated using an experimental approach to simulate gene pyramiding in potato. Potato plants transgenic for both the crylAc9 and cryAa2 genes were developed and evaluated to help provide a more durable resistance to potato tuber moth.

A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country.

The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources.

Anti-tumor and anti-vascular effects of the novel tubulin-binding agent combretastatin A-1 phosphate.

The combretastatins are derived from an African medicinal plant Combretum caffrum (Combretaceae). They have previously been shown to be potent inhibitors of microtubule assembly that cause marked haemorrhagic necrosis in murine subcutaneous tumors. Promising clinical trial results with combretastatin A-4 phosphate led to this investigation of the anti-tumor and anti-vascular effects of a close structural analog, combretastatin A-1 phosphate. This compound caused identical disruption of the tubulin cytoskeleton in HUVECs in vitro at similar concentrations and duration of exposure as combretastatin A-4 phosphate. Treatment of a well-vascularised murine colon adenocarcinoma (MAC 29) with an effective dose (150 mg/kg) of combretastatin A-1 phosphate resulted in a dramatic decrease in functional vascular volume 2 hours after administration. Vascular shutdown was complete within 4 hours after treatment apart from in small areas of the tumor periphery. Morphological examination of hepatic deposits of HT29 and DLD-1 human colon tumors in nude mice demonstrated that combretastatin A-1 phosphate displays greater anti-tumor effects than the A-4 analog at the same dose and this order of activity (A-1 > A-4) is mirrored in the subcutaneous site with the same tumor type. In summary, combretastatin A-1 phosphate can exert its anti-tumor action via an anti-vascular mechanism. The results indicate that, despite having similar in vitro anti-tubulin properties, combretastatin A-1 phosphate seems to have greater in vivo anti-tumor activity than combretastatin A-4 phosphate at the same doses and may therefore be more successful in the clinic.

Comparative growth and biochemical response of very low birthweight infants fed own mother's milk, a premature infant formula, or one of two standard formulas.

Very low birthweight (VLBW) infants weighing less than 1,600 g at birth were fed their own mother's milk (OMM) or randomly assigned to receive one of three formulas: a "humanized" formula (SF), a partially modified casein-predominant cow's milk formula (CF), or a premature formula (PF). All infants were fed at 120 kcal/kg/day where possible. PF infants had significantly greater weight increments (28.0 g/day) than those on OMM (19.4 g/day), SF (18.9 g/day), and CF (18.2 g/day). Those on PF also had greater increments of length, head circumference, and skin-fold thickness than those on the other two formulas and greater length increments than those on OMM. Dynamic skinfold measurements suggested that no infants accumulated excessive amounts of interstitial fluid. Infants on the two standard formulas had significantly greater base deficits, whereas those on CF also had higher urea values. Those on OMM had lower phosphate and higher alkaline phosphatase values than the other groups. Thus VLBW infants fed a premature formula had better growth and fewer biochemical problems than those on standard formulas, whereas supplementation of OMM may be necessary to ensure optimal growth and bone mineralization.

Threshold for initiation of phototherapy in infants with non-haemolytic hyperbilirubinaemia.

The effect of initiating phototherapy at three different bilirubin concentrations in infants with physiological jaundice was studied in 98 clinically jaundiced term infants. Phototherapy was initiated at levels of 170, 257 and 300 mumol/l in groups A, B and C respectively. There was no difference between the groups in terms of days in hospital and bilirubin levels at entry or at exit from the study. Of group A, 97% received phototherapy v. 47% and 18% in groups B and C respectively. Peak bilirubin in those infants in group C receiving phototherapy was 318 mumol/l v. 282 mumol/l and 229 mumol/l in groups A and B. Two group C infants suffered complications of hyperbilirubinaemia. Rebound hyperbilirubinaemia was noted in infants with more severe jaundice after cessation of phototherapy. The threshold for toxicity in non-haemolytic hyperbilirubinaemia may be higher than the still widely accepted 340 mumol/l value, but pending definitive studies phototherapy will continue to be initiated at levels of greater than 257 mumol/l in term infants with hyperbilirubinaemia.