Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive Helicoverpa pest species.

BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. RESULTS: We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.

The use of a dental implant as an abutment in three unit implant-tooth supported fixed partial denture: a case report and 32 month follow-up.

The combined use of dental implants and teeth as abutments in fixed partial dentures may offer advantages to both patients and practitioners in certain clinical situations. An implant-tooth retained prosthesis may reduce surgical intervention and cost to the patient. It may also mean that anatomical restrictions to the provision of an implant-retained fixed prosthesis may be overcome. In this case report, the steps in provision of a three unit implant-to-tooth fixed partial denture are described and the treatment planning and prognosis of a restoration of this type are discussed.

Nevirapine: pharmacokinetic considerations in children and pregnant women.

Nevirapine is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase. It is effective when used as part of combination therapy to treat HIV-1-infected individuals and as monotherapy for prevention of mother-to-child HIV-1 transmission. Nevirapine pharmacokinetics are characterised by rapid absorption and distribution, followed by prolonged elimination. Nevirapine is generally well tolerated. The most common toxicity is rash, which is usually mild and self-limiting. The primary route of nevirapine elimination is through metabolism by the cytochrome P450 enzyme system. Nevirapine elimination accelerates during long term administration because of autoinduction of the enzymes involved in its elimination pathway. The recommended regimen for adults is nevirapine 200mg once daily for 2 weeks, followed by 200mg twice daily. Nevirapine elimination is prolonged in pregnant women during labour and in newborns. A regimen of a single 200mg oral dose administered to the mother during labour and a single 2 mg/kg dose administered to the newborn at 48 to 72 hours after birth maintains serum nevirapine concentrations above 100 microg/L (10 times the in vitro 50% inhibitory concentration against wild-type HIV-1) throughout the first week of life. This limited regimen has been shown to be extremely well tolerated and to reduce mother-to-child transmission by nearly 50% in mothers and infants receiving no other antiretrovirals. There are few data describing the safety and pharmacokinetics of nevirapine during long term use in pregnancy. In children, nevirapine elimination accelerates during the first years of life, reaching a maximum at around 2 years of age, followed by a gradual decline during the rest of childhood. Children should receive 4 mg/kg once daily for the first 2 weeks of therapy, followed by 7 mg/kg doses twice daily if below the age of 8 years or 4 mg/kg twice daily if older than 8 years. Alternatively, children may receive 150 mg/m2 across all ages, once daily for the first 2 weeks of therapy followed by the same dose twice daily.

Bioequivalence of a propylene glycol-based liquid dapsone preparation and dapsone tablets.

The bioequivalence of a proprietary liquid dapsone preparation and commercially available dapsone tablets was studied. Twelve adult volunteers received dapsone doses with 8 oz of water one to two hours after their usual breakfast. Each subject received an initial 100-mg dose of a propylene glycol-based liquid preparation of dapsone and, two weeks later, a 100-mg dapsone tablet (both from Jacobus Pharmaceutical Company, Princeton, NJ). Blood samples were collected before and at intervals up to 96 hours after the administration of each dose. Serum dapsone concentrations were determined by high-performance liquid chromatography, and pharmacokinetic values were calculated by model-independent analysis. The area under the concentration-versus-time curve and the maximum serum concentration for the two formulations met the criteria for bioequivalence. Time to maximum serum concentration tended to be lower for the liquid, but not significantly. The liquid and tablet formulations of dapsone studied were found to be bioequivalent and may be used interchangeably.

Comparison between two procion dyes and alizarin red to assess marginal leakage in resin restorations. A laboratory study.

To assess the width of the gaps that may occur in resin restorations bonded to dentine, buccal and lingual cavities were prepared in 18 caries- and restoration-free extracted molar teeth. All teeth were restored with composite resin. Nine of the teeth were then thermocycled for five hours. All teeth were stained with 0.5 per cent, 1.0 per cent or 1.5 per cent solutions of chloro-s-triazinyl dyes (Reactive Red and Reactive Orange 14) or Alizarin Red in order to assess the effectiveness of each stain in detecting marginal leakage. Quantitative assessment indicated that Reactive Orange 14 was superior to the other two stains as it more clearly defined the marginal gaps of the restorations. This superiority was evident for both thermocycled and nonthermocycled teeth.

Conversion from intravenous to sustained-release oral theophylline in pediatric patients with asthma.

A method for converting pediatric patients from intravenous aminophylline to sustained-release oral theophylline was evaluated in eight asthmatic children. The administration of Theo-Dur tablets two hours before discontinuation of a continuous intravenous aminophylline infusion resulted in a peak rise of 5.6 +/- 3.0 micrograms/ml over steady-state serum theophylline concentrations. This method of conversion is acceptable in children with equivalent oral and intravenous doses of theophylline and serum theophylline concentrations less than 15 micrograms/ml. Children with steady-state theophylline concentrations greater than 15 micrograms/ml are likely to develop concentrations exceeding the therapeutic range using this conversion method.

Sulfasalazine metabolite pharmacokinetics in pediatric patients with inflammatory bowel disease: effects of disease activity, acetylator phenotype, and age.

The pharmacokinetics and protein binding of sulfapyridine (SP) and its major metabolite, acetylsulfapyridine (ACSP) were examined in 17 prepubertal children and 4 postpubertal adolescents receiving sulfasalazine (SASP) for treatment of inflammatory bowel disease (IBD). Five patients were studied in both active disease and remission. Comparisons were made with a group of 24 outpatients (9-62 years) with IBD controlled on SASP and in remission. Acetylator phenotype was calculated from plasma metabolite ratios. Slow acetylators had increased plasma concentrations of SP and ACSP + SP (P less than 0.05). Apparent SP clearance (clearance/availability) was increased in active disease (P less than 0.05) and AUCSP + ACSP and AUCSP were decreased (P less than 0.05). There were no age-related alterations in apparent SP clearance. Side effects were frequent but were unrelated to SASP dose, SP concentrations, or acetylator phenotype. Disease activity did not significantly alter the serum protein binding of SP or ACSP. The decreased SP and ACSP concentrations seen in active disease may be due to a combination of disease related alterations in either cleavage of SASP or absorption and clearance of SP.