Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes

Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes

Improvement in Renal Function and Reduction in Serum Uric Acid with Intensive Statin Therapy in Older Patients: A Post Hoc Analysis of the SAGE Trial

BACKGROUND: Improvement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65–85 years) with or without chronic kidney disease (CKD). METHODS: Patients were randomized to atorvastatin 80 mg/day or pravastatin 40 mg/day and treated for 12 months. Patients were stratified using Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rates (eGFRs) in CKD (eGFR <60 mL/min/1.73 m(2)) and non-CKD populations. RESULTS: Of the 893 patients randomized, 858 had complete renal data and 418 of 858 (49 %) had CKD (99 % Stage 3). Over 12 months, eGFR increased with atorvastatin and remained stable with pravastatin (+2.38 vs. +0.18 mL/min/1.73 m(2), respectively; p < 0.0001). MDRD eGFR improved significantly in both CKD treatment arms; however, the increased eGFR in patients without CKD was significantly greater with atorvastatin (+2.08 mL/min/1.73 m(2)) than with pravastatin (−1.04 mL/min/1.73 m(2)). Modest reductions in SUA were observed in both treatment arms, but a greater fall occurred with atorvastatin than with pravastatin (−0.52 vs. −0.09 mg/dL, p < 0.0001). Change in SUA correlated negatively with changes in eGFR and positively with changes in low-density lipoprotein cholesterol. Reports of myalgia were rare (3.6 % CKD; 5.7 % non-CKD), and there were no episodes of rhabdomyolysis. Elevated serum alanine and aspartate transaminase to >3 times the upper limit of normal occurred in 4.4 % of atorvastatin- and 0.2 % of pravastatin-treated patients. CONCLUSION: Intensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA