Prospects for control of African trypanosomiasis by tsetse vector manipulation

The extensive antigenic variation phenomena African trypanosomes display in their mammalian host have hampered efforts to develop effective vaccines against trypanosomiasis. Human disease management aims largely to treat infected hosts by chemotherapy, whereas control of animal diseases relies on reducing tsetse populations as well as on drug therapy. The control strategies for animal diseases are carried out and financed by livestock owners, who have an obvious economic incentive. Sustaining largely insecticide-based control at a local level and relying on drugs for treatment of infected hosts for a disease for which there is no evidence of acquired immunity could prove extremely costly in the long run. It is more likely that a combination of several methods in an integrated, phased and area-wide approach would be more effective in controlling these diseases and subsequently improving agricultural output. New approaches that are environmentally acceptable, efficacious and affordable are clearly desirable for control of various medically and agriculturally important insects including tsetse. Here, Serap Aksoy and colleagues discuss molecular genetic approaches to modulate tsetse vector competence.

Population subdivision in marine environments: the contributions of biogeography, geographic distance, and discontinuous habitat to genetic differentiation in a blennioid

The relative importance of factors that may promote genetic differentiation in marine organisms is largely unknown. Here, contributions to population structure from biogeography, habitat distribution, and isolation by distance were investigated in Axoclinus nigricaudus, a small subtidal rock reef fish, throughout its range in the Gulf of California. A 408 basepair fragment of the mitochondrial control region was sequenced from 105 individuals. Variation was significantly partitioned between many pairs of populations. Phylogenetic analyses, hierarchical analyses of variance, and general linear models substantiated a major break between two putative biogeographic regions. This genetic discontinuity coincides with an abrupt change in ecological characteristics (including temperature and salinity) but does not coincide with known oceanographic circulation patterns. Geographic distance and the nature of habitat separating populations (continuous habitat along a shoreline, discontinuous habitat along a shoreline, and open water) also contributed to population structure in general linear model analyses. To verify that local populations are genetically stable over time, one population was resampled on four occasions over eighteen months; it showed no evidence of a temporal component to diversity. These results indicate that having a planktonic life stage does not preclude geographically partitioned genetic variation over relatively small geographic distances in marine environments. Moreover, levels of genetic differentiation among populations of Axoclinus nigricaudus cannot be explained by a single factor, but are due to the combined influences of a biogeographic boundary, habitat, and geographic distance.

Incubation of turtle eggs at different temperatures: Do embryos compensate for temperature during development?

Freshwater turtle eggs are normally subjected to fluctuations in incubation temperature during natural incubation. Because of this, developing embryos may make physiological adjustments to growth and metabolism in response to incubation at different temperatures. I tested this hypothesis by incubating eggs of the Brisbane river turtle Emydura signata under four different temperature regimes, constant temperatures of 24 degrees C and 31 degrees C throughout incubation, and two swapped-temperature treatments where incubation temperature was changed approximately halfway through incubation. Incubation at 31 degrees C took 42 d, and incubation at 24 degrees C look 78 d, with intermediate incubation periods for the swapped-temperature treatments. Hatchling mass, hatchling size, and total oxygen consumed during development were similar for all incubation regimes. The pattern of oxygen consumption during the last phase of incubation as reflected by rate of increase of oxygen consumption, peak oxygen consumption, and fall in oxygen consumption before hatching was determined solely by the incubation temperature during the last phase of incubation; that is, incubation temperature during the first phase of incubation had no influence on these factors. Thus there is no evidence of temperature compensation in growth or development during embryonic development of E. signata eggs.

The treatment of tardive dyskinesia: A systematic review and meta-analysis

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for mete-analysis, Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Metaanalysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects. (C) 1999 Elsevier Science B.V. All rights reserved.

Delayed postural contraction of transversus abdominis in low back pain associated with movement of the lower limb

The temporal parameters of the response of the trunk muscles associated with movement of the lower limb were investigated in people with and without low back pain (LBP). The weight shift component of the task was completed voluntarily prior to a stimulus to move to allow investigation of the movement component of the response. In the control subjects the onset of electromyographic (EMG) activity of all trunk muscles preceded that of the muscle responsible for limb movement, thus contributing to the feed forward postural response. The EMG onset of transversus abdominis was delayed in the LBP subjects with movement in each direction, while the EMG onsets of rectus abdominis, erector spinae, and oblique abdominal muscles were delayed with specific movement directions. This result provides evidence of a change in the postural control of the trunk in people with LBP.

Targeting of a cholecystokinin-DNA complex to pancreatic cells in vitro and in vivo

The carboxy terminal octapeptide of cholecystokinin (CCK8) is a hormone that binds high affinity receptors in a number of tissues including pancreas and pancreatic tumours. As part of our studies to develop effective gene therapy for the treatment of pancreatic cancers, we have investigated various gene delivery systems that depend on CCK8 receptor targeting. In this paper,we describe the synthesis of a CCK8-DNA complex designed to deliver foreign DNA to cholecystokinin receptor-positive cells. CCK8 was ligated to avidin and then complexed to linearis biotinylated DNA (pSV-CAT). The uptake of P-32-labelled CCK8-DNA complex by rat pancreatic acini was linear with time over 4 h with 65-70% of uptake inhibited by 100 nM CCK8. The complex appeared to be internalised since it could not be removed by acid wash. When administered intra-arterially, the complex was rapidly removed from the circulation with no evidence of targeted delivery to the pancreas, However, following a single intraperitoneal dose, the pancreas accumulated-5- 8% of the total administered complex by 24 h. These results suggest that peptide-dependent gene delivery to CCK receptor positive cells in vivo is feasible but, when administered directly into the circulation, diffusional barriers across the endothelium may limit distribution to peripheral tissues. Intraperitoneal administration therefore may be a useful alternative for targeting the pancreas.