Biochemical basis of permethrin resistance in Anopheles arabiensis from Lower Moshi, north-eastern Tanzania.

BACKGROUND: Development of resistance to different classes of insecticides is a potential threat to malaria control. With the increasing coverage of long-lasting insecticide-treated nets in Tanzania, the continued monitoring of resistance in vector populations is crucial. It may facilitate the development of novel strategies to prevent or minimize the spread of resistance. In this study, metabolic-based mechanisms conferring permethrin (pyrethroid) resistance were investigated in Anopheles arabiensis of Lower Moshi, Kilimanjaro region of north-eastern Tanzania. METHODS: WHO susceptibility test kits were used to detect resistance to permethrin in An. arabiensis. The levels and mechanisms of permethrin resistance were determined using CDC bottle bioassays and microplate (biochemical) assays. In bottle bioassays, piperonyl butoxide (PBO) and s,s,s-tributyl phosphorotrithioate (DEF) were used as synergists to inhibit mixed function oxidases and non-specific esterases respectively. Biochemical assays were carried out in individual mosquitoes to detect any increase in the activity of enzymes typically involved in insecticide metabolism (mixed function oxidases, alpha- and beta-esterases). RESULTS: Anopheles arabiensis from the study area was found to be partially resistant to permethrin, giving only 87% mortality in WHO test kits. Resistance ratios at KT50 and KT95 were 4.0 and 4.3 respectively. The permethrin resistance was partially synergized by DEF and by PBO when these were mixed with permethrin in bottle bioassays and was fully synergized when DEF and PBO were used together. The levels of oxidase and beta-esterase activity were significantly higher in An. arabiensis from Lower Moshi than in the laboratory susceptible strain. There was no difference in alpha-esterase activity between the two strains. CONCLUSION: Elevated levels of mixed function oxidases and beta-esterases play a role in detoxification of permethrin in the resistant An. arabiensis population of Lower Moshi.

Trapidil decreases the aggregation of platelets from heart transplant recipients ex vivo.

Heart transplant recipients show platelet hyperaggregability, which may be related to the incidence of graft vasculopathy. We investigated whether trapidil can inhibit the aggregation of platelets from these patients. Platelet count, mean platelet volume (MPV), and adenosine diphosphate (ADP)-induced platelet aggregation were determined in 18 heart transplant recipients and 12 healthy subjects. Additionally, platelet-rich plasma from the patients was incubated with trapidil or with saline, prior to measuring ADP-induced aggregation. The MPV was significantly greater in patients compared to controls (9.4+/-1.1 vs 8.5+/-0.7 fL; P=.01), and ADP-induced platelet aggregation was significantly increased in patients compared to controls (81.2%+/-13.1% vs 69.6%+/-16.2%; P=.04, respectively). The trapidil-treated samples showed significantly decreased platelet aggregation compared to the control samples (24.2%+/-12.6% vs 66.7%+/-11.7%; P<.001). Platelets from heart transplant recipients showed an increased MPV and increased ADP-induced aggregation. Trapidil effectively reduced the ADP-induced aggregation ex vivo.

Atrial fibrillation at discharge from the hospital in patients undergoing mitral valve repair.

BACKGROUND: Patients undergoing mitral valve repair (MVRr) are often discharged on oral anticoagulation with warfarin. Because the decision about oral anticoagulation is made at discharge from the hospital and because atrial fibrillation (AF) represents the only well-documented indication for oral anticoagulation in these patients, we studied the frequency of AF at discharge after MVRr. METHODS: We reviewed the records of 245 patients who underwent MVRr over the past 5 years and assessed the frequency of AF at discharge from the hospital and the factors that were associated with an increased risk for arrhythmia. RESULTS: The group comprised 95 women and 150 men with a mean age of 62.1 +/- 14 years. Seventy-three (30 %) patients were in and/or had a history of AF on admission. Sixty-five (27 %) patients had AF at discharge. Factors that were associated with AF at discharge were: AF on admission (odds ratio [OR] 57.1; confidence interval [CI] 20.8 - 157.3; p < 0.0001), enlarged left atrium (OR 3.2; CI 1.2 - 8.7; p = 0.025) and intake of ACE inhibitors (OR 3.9; CI 1.2 - 12.3; p = 0.022). The OR for AF at discharge in patients with none of the above risk factors was 0.02 (95 % CI 0.02 - 0.13; p < 0.0001). CONCLUSION: Only a relatively small proportion of the studied patients, especially patients with AF on admission, with larger atria and with a history of ACE inhibitors intake, were in AF at discharge after MVRr. Patients with none of these risk factors were at low risk for AF at discharge after MVRr and the optimal oral anticoagulation regimen for these low-risk patients needs to be determined.