Feeding response of Aedes aegypti and Anopheles dirus (Diptera: Culicidae) using out-of-date human blood in a membrane feeding apparatus.

The colonization of Aedes aegypti and Anopheles dirus was performed using out-of-date human blood from a blood bank as a nutritional supply dispensed from a common artificial feeder. Preserved human blood was collected and used for feeding on days 5, 15, and 25 after date of expiration and dispensed from a common artificial feeder to rear the mosquitoes. Ae. aegypti had a feeding rate of 78.7, 62, and 18% at the respective intervals while An. dirus had a rate of 80, 56.8, and 7.3% on the same respective days. Direct feeding on live hamsters resulted in a rate of 96 and 90% for Ae. aegypti and An. dirus, respectively. Although egg production rates decreased from the day 5 feeding to the day 25 feeding, all of the developmental stages resulting from An. dirus fed at day 5 and 15 showed insignificant differences when compared with direct feeding on the blood of a hamster.

Susceptibility of various mosquitoes of Thailand to nocturnal subperiodic Wuchereria bancrofti.

Ten different mosquito species representing five genera were allowed to feed on human blood containing microfilariae (5.5-6.5 mf/microl) of nocturnal subperiodic Wuchereria bancrofti from Kanchanaburi Province, Thailand. Aedes aegypti, Aedes albopictus, Aedes desmotes, Downsiomyia species (=Finlaya Niveus Group), Culex quinquefasciatus, Anopheles dirus A, An. maculatus, An. minimus, Armigeres subalbatus, and Mansonia uniformis were fed under laboratory conditions using an artificial membrane feeding procedure. All species had adequate feeding responses (68-87.3%) and survival (66.4-81.3%) 12-15 days post-feeding. Anopheles maculatus was the most susceptible (73.1%) for development of infective third-stage larvae (L3), followed by An. minimus (61.0%), Downsiomyia species (27.3%), Ae. desmotes (24.2%), An. dirus A (24.7%), Cx. quinquefasciatus (19.2%), Ma. uniformis (9.2%), and Ae. albopictus (0.01%). Aedes aegypti and Ar. subalbatus were found to be completely refractory. An. maculatus produced the greatest mean number of L3 per infective mosquito (5.6 L3) and Ae. albopictus the least (1 L3). The two Anopheles demonstrated significantly greater susceptibility (P<0.05%) to W. bancrofti than the two Aedes species regarded as natural vectors.

Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease.

Studies on postmortem brains from Parkinson's patients reveal elevated iron in the substantia nigra (SN). Selective cell death in this brain region is associated with oxidative stress, which may be exacerbated by the presence of excess iron. Whether iron plays a causative role in cell death, however, is controversial. Here, we explore the effects of iron chelation via either transgenic expression of the iron binding protein ferritin or oral administration of the bioavailable metal chelator clioquinol (CQ) on susceptibility to the Parkinson's-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrapyridine (MPTP). Reduction in reactive iron by either genetic or pharmacological means was found to be well tolerated in animals in our studies and to result in protection against the toxin, suggesting that iron chelation may be an effective therapy for prevention and treatment of the disease.

Inhibition of caspases protects cerebellar granule cells of the weaver mouse from apoptosis and improves behavioral phenotype.

The homozygous mouse mutant weaver exhibits a massive loss of cerebellar granule neurons postnatally. The death of these cells is associated with a single amino acid mutation in the G protein-activated inwardly rectifying potassium channel, Girk2. Evidence suggests that both the mutated Girk2 channel and the calcium channel-associated N-methyl-d-aspartate receptor play important roles in the apoptotic death of weaver cerebellar granule cells, but the downstream events associated with this process are unknown. In this study, we demonstrate that the consequences of the mutation result in caspase activation. In addition, our results show that caspase inhibition in vivo decreases caspase activation and granule cell apoptosis and significantly improves behavioral deficits associated with the weaver's phenotype.

Glutathione decreases in dopaminergic PC12 cells interfere with the ubiquitin protein degradation pathway: relevance for Parkinson's disease?

Parkinson's disease (PD) is characterized by the presence of proteinaceous neuronal inclusions called Lewy bodies in susceptible dopaminergic midbrain neurons. Inhibition of the ubiquitin-proteasome protein degradation pathway may contribute to protein build-up and subsequent cell death. Ubiquitin is normally activated for transfer to substrate proteins by interaction with the E1 ubiquitin ligase enzyme via a thiol ester bond. Parkinson's disease is also characterized by decreases in midbrain levels of total glutathione which could impact on E1 enzyme activity via oxidation of the active site sulfhydryl. We have demonstrated that increasing reductions in total glutathione in dopaminergic PC12 cells results in corresponding decreases in ubiquitin-protein conjugate levels suggesting that ubiquitination of proteins is inhibited in a glutathione-dependent fashion. Decreased ubiquitinated protein levels appears to be due to inhibition of E1 activity as demonstrated by reductions in endogenous E1-ubiquitin conjugate levels as well as decreases in the production of de novo E1-ubiquitin conjugates when glutathione is depleted. This is a reversible process as E1 activity increases upon glutathione restoration. Our data suggests that decreases in cellular glutathione in dopaminergic cells results in decreased E1 activity and subsequent disruption of the ubiquitin pathway. This may have implications for neuronal degeneration in PD.