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Sample records for polyester-based long-lasting insecticidal

  1. Evidence for a useful life of more than three years for a polyester-based long-lasting insecticidal mosquito net in Western Uganda

    PubMed Central

    2011-01-01

    Background Long-lasting insecticidal nets (LLIN) are now standard for the prevention of malaria. However, only products with recommendation for public use from the World Health Organization should be used and this evaluation includes the assessment of net effectiveness after three years of field use. Results for one of the polyester-based products, Interceptor® is presented. Methods In five villages, 190 LLIN and 90 nets conventionally treated with the insecticide alpha-cypermethrin at 25 mg/m2 were distributed randomly and used by the families. Following a baseline household survey a net survey was carried out every six months to capture use, washing habits and physical condition of the nets. Randomly selected nets were collected after 6, 12, 24, 36 and 42 months and tested for remaining insecticide content and ability to knock-down and kill malaria transmitting mosquitoes. Results During the three and a half years of observation only 16 nets were lost to follow-up resulting in an estimated attrition rate of 12% after three and 20/% after 3.5 years. Nets were used regularly and washed on average 1.5 times per year. After three and a half years 29% of the nets were still in good condition while 13% were seriously torn with no difference between the LLIN and control nets. The conventionally treated nets quickly lost insecticide and after 24 months only 7% of the original dose remained (1.6 mg/m2). Baseline median concentration of alpha-cypermethrin for LLIN was 194.5 mg/m2 or 97% of the target dose with between and within net variation of 11% and 4% respectively (relative standard deviation). On the LLIN 73.8 mg/m2 alpha-cypermethrin remained after three years of use and 56.2 mg/m2 after three and a half and 94% and 81% of the LLIN still had > 15 mg/m2 left respectively. Optimal effectiveness in bio-assays (≥95% 60 minute knock-down or ≥ 80% 24 hour mortality) was found in 83% of the sampled LLIN after three and 71% after three and a half years. Conclusions

  2. Long-term field performance of a polyester-based long-lasting insecticidal mosquito net in rural Uganda

    PubMed Central

    Kilian, Albert; Byamukama, Wilson; Pigeon, Olivier; Atieli, Francis; Duchon, Stephan; Phan, Chi

    2008-01-01

    Background In order to evaluate whether criteria for LLIN field performance (phase III) set by the WHO Pesticide Evaluation Scheme are met, first and second generations of one of these products, PermaNet®, a polyester net using the coating technology were tested. Methods A randomized, double blinded study design was used comparing LLIN to conventionally treated nets and following LLIN for three years under regular household use in rural conditions. Primary outcome measures were deltamethrin residue and bioassay performance (60 minute knock-down and 24 hour mortality after a three minute exposure) using a strain of Anopheles gambiae s.s. sensitive to pyrethroid insecticides. Results Baseline concentration of deltamethrin was within targets for all net types but was rapidly lost in conventionally treated nets and first generation PermaNet® with median of 0.7 and 2.5 mg/m2 after six months respectively. In contrast, second generation PermaNet® retained insecticide well and had 41.5% of baseline dose after 36 months (28.7 mg/m2). Similarly, vector mortality and knockdown dropped to 18% and 70% respectively for first generation LLIN after six months but remained high (88.5% and 97.8% respectively) for second generation PermaNet® after 36 months of follow up at which time 90.0% of nets had either a knockdown rate ≥ 95% or mortality rate ≥ 80%. Conclusion Second generation PermaNet® showed excellent results after three years of field use and fulfilled the WHOPES criteria for LLIN. Loss of insecticide on LLIN using coating technology under field conditions was far more influenced by factors associated with handling rather than washing. PMID:18355408

  3. Evidence of man-vector contact in torn long-lasting insecticide-treated nets

    PubMed Central

    2013-01-01

    Background Studies indicate that physical damage to long-lasting insecticide-treated nets (LLINs) occurs at a surprisingly rapid rate following net distribution. To what extent does such damage affect the impact of LLINs? Can vectors pass a compromised LLIN barrier to bite? Do more resistant vectors enter the insecticide-treated nets (ITNs) through holes? Methods The study was carried out in three geo-locations. Two types of LLINs (polyester and polyethylene) with ‘standardized’ physical damage were compared with similarly damaged, but non-insecticidal (control) nets. The proportionate Holes Index (pHI) of each net was 276. Mosquitoes were captured inside the nets, identified taxonomically, and subjected to molecular analysis to estimate Knock-down resistance (Kdr) frequency. Results The most commonly observed species was Anopheles gambiae, accounting for approximately 70% (1,076/1,550) of the total mosquitoes collected both in LLINs and non-insecticidal nets. When compared with controls, number of vectors captured in torn LLINs was significantly reduced. Nonetheless in a night, an average of 5 An. gambiae s.l could enter the damaged LLINs to bite. Similar numbers of resistant mosquitoes were collected in both LLINs and non-insecticidal (control) nets (p > 0.05). Conclusions At a pHI of 276, man-vector contact was observed in torn LLINs. The insecticide at the surface of LLINs could only reduce the number of vectors. Resistant mosquitoes have opportunity to enter both non-insecticidal (control) nets and LLINs to bite. PMID:23941585

  4. Net Risk: A Risk Assessment of Long-Lasting Insecticide Bed Nets Used for Malaria Management

    PubMed Central

    Peterson, Robert K. D.; Barber, Loren M.; Schleier, Jerome J.

    2011-01-01

    Despite the demonstrated ability of bed nets that have been factory-impregnated with long-lasting insecticides (LLINs) to protect people from malaria and despite the ambitious plans for their widespread use, the health risks from the LLINs themselves have not been adequately investigated and reported in the peer-reviewed science literature. Here, we use a probabilistic risk assessment approach to estimate the risks to Africans from inhalation, dermal, and oral exposures to the newer LLINs with permethrin, α-cypermethrin, or deltamethrin as the insecticide active ingredient. We estimated exposures to LLINs using 17 age groups to incorporate different body weights and sleeping behaviors. Risk quotients (exposure divided by toxic threshold) at the 50th and 90th percentiles for non-cancer risks were < 1.0 for lifetime adjusted risk and all youth and adult age groups. Risk quotients for infants and toddlers (0–3 years) and child groups from 3 to 10 years were ≥ 1.0 for specific bed nets. PMID:21633033

  5. The effects of washing and duration of use of long-lasting insecticidal nets (PermaNets) on insecticidal effectiveness.

    PubMed

    Msangi, S; Lyatuu, E; Masenga, C; Kihumo, E

    2008-07-01

    The use of insecticide-treated nets (ITNs) is one of the most feasible weapons available for malaria control in Africa today. One of the important requirements for ITN use is regular re-treatment at an appropriate time. As a response to the low re-treatment rate when the ITN users are expected to purchase insecticide and re-treat their nets, manufacturers have developed long-lasting insecticidal nets (LLIN) that are pre-treated in the factory, and are claimed to require no further treatment during their lifespan. A study was conducted to assess the possible effects of number of washings, frequency of washing and the duration of use on the effectiveness of PermaNets, a LLIN, against mosquitoes. The study was done for 9 months at Chekereni village, Northeastern Tanzania. The LLINs and untreated control nets were distributed to villagers in three groups. Group 1 nets were used without being washed for the whole study period. Group 2 nets received one wash per month, while group 3 received two washes per month. The effectiveness was assessed by contact bioassays using World Health Organization (WHO) bioassay cones. Mosquitoes were exposed to the netting for 3min. The knock down and mortality was scored after 3min and 24h, respectively. Results showed that the number and frequency of washes had no significant effect on the efficacy for up to 18 washes. Similarly, we could not detect a significant effect of duration of use and conditions of use on the efficacy for up to 9 months. PermaNets caused short-lived irritation and sneezing but appear to be well accepted by the community in which the study was conducted. PMID:18502395

  6. Africa's largest long-lasting insecticide-treated net producer: lessons from A to Z Textiles

    PubMed Central

    2010-01-01

    Background Field trials have demonstrated the efficacy of insecticide-treated nets, and the WHO has recently endorsed a shift toward Long-Lasting Insecticide Treated nets (LLINs) due to factors such as reduced distribution costs. However, the need for LLINs poses several challenges. Is it possible to manufacture LLINs in large quantities in the African continent, where malaria is most endemic? When production is located in low-income countries, what role is played by local funding and employment, scaling up manufacturing, and partnerships? What factors influence availability and pricing? Discussion A case study of A to Z Textiles was undertaken to answer the question of how large-scale production of LLINs can occur in a low income setting. One of the largest sources of bed nets for Africa, A to Z Textiles is Africa-based, and its Tanzanian operations have a production capacity of 30 million LLINs per year, along with full WHO recommendation for its nets. Our analysis is based on semi-structured interviews with key informants familiar with A to Z, site visits in Tanzania, and literature reviews. This paper discusses the history and current status of A to Z Textiles, identifies the factors that led to its success, and suggests policy considerations that could support similar initiatives in the future. Local funding, scaling up manufacturing, technology transfer, and partnerships all played important roles in A to Z’s ascent, as did perceived benefits of local employment and capacity-building. Regulatory issues and procurement rules acted as barriers. A to Z cost-effectively manufactures high-quality LLINs where malaria is most endemic. Summary With a production capacity of 30 million LLINs per year, and full WHOPES (WHO Pesticide Evaluation Scheme) certification, A to Z Textiles demonstrates how key health goods can be successfully produced in the low-income countries that use them. Its example may be instructive and of high interest to readers in the malaria

  7. System effectiveness of a targeted free mass distribution of long lasting insecticidal nets in Zanzibar, Tanzania

    PubMed Central

    2010-01-01

    Background Insecticide-treated nets (ITN) and long-lasting insecticidal treated nets (LLIN) are important means of malaria prevention. Although there is consensus regarding their importance, there is uncertainty as to which delivery strategies are optimal for dispensing these life saving interventions. A targeted mass distribution of free LLINs to children under five and pregnant women was implemented in Zanzibar between August 2005 and January 2006. The outcomes of this distribution among children under five were evaluated, four to nine months after implementation. Methods Two cross-sectional surveys were conducted in May 2006 in two districts of Zanzibar: Micheweni (MI) on Pemba Island and North A (NA) on Unguja Island. Household interviews were conducted with 509 caretakers of under-five children, who were surveyed for socio-economic status, the net distribution process, perceptions and use of bed nets. Each step in the distribution process was assessed in all children one to five years of age for unconditional and conditional proportion of success. System effectiveness (the accumulated proportion of success) and equity effectiveness were calculated, and predictors for LLIN use were identified. Results The overall proportion of children under five sleeping under any type of treated net was 83.7% (318/380) in MI and 91.8% (357/389) in NA. The LLIN usage was 56.8% (216/380) in MI and 86.9% (338/389) in NA. Overall system effectiveness was 49% in MI and 87% in NA, and equity was found in the distribution scale-up in NA. In both districts, the predicting factor of a child sleeping under an LLIN was caretakers thinking that LLINs are better than conventional nets (OR = 2.8, p = 0.005 in MI and 2.5, p = 0.041 in NA), in addition to receiving an LLIN (OR = 4.9, p < 0.001 in MI and in OR = 30.1, p = 0.001 in NA). Conclusions Targeted free mass distribution of LLINs can result in high and equitable bed net coverage among children under five. However, in order to sustain

  8. Planning long lasting insecticide treated net campaigns: should households’ existing nets be taken into account?

    PubMed Central

    2013-01-01

    Background Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. Methods A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net ‘decay’ parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered

  9. Long-Lasting Insecticidal Nets Are Synergistic with Mass Drug Administration for Interruption of Lymphatic Filariasis Transmission in Nigeria

    PubMed Central

    Eigege, Abel; Miri, Emmanuel; Sallau, Adamu; Umaru, John; Mafuyai, Hayward; Chuwang, Yohanna S.; Danjuma, Goshit; Danboyi, Jacob; Adelamo, Solomon E.; Mancha, Bulus S.; Okoeguale, Bridget; Patterson, Amy E.; Rakers, Lindsay; Richards, Frank O.

    2013-01-01

    In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission. PMID:24205421

  10. The effect of long-lasting insecticidal water container covers on field populations of Aedes aegypti (L.) mosquitoes in Cambodia.

    PubMed

    Seng, Chang Moh; Setha, To; Nealon, Joshua; Chantha, Ngan; Socheat, Doung; Nathan, Michael B

    2008-12-01

    Dengue in Cambodia is mainly transmitted by Aedes aegypti (L.) mosquitoes that primarily breed in large, concrete jars (> or =200 liters) used for the storage of water for domestic use. Following a preliminary risk assessment, long-lasting insecticidal netting (LN) treated with deltamethrin was incorporated into the design of the covers for these jars. Their effect on immature and adult female populations of Ae. aegypti in six villages in a peri-urban area of Cambodia were compared with populations in six nearby control villages before and for 22 weeks after distribution of the jar covers. There were significantly fewer pupae per house in intervention villages than in control villages (6.6 and 31.9, respectively, p<0.01). Fewer pupae were recovered from intervention houses than from control houses at every post-intervention assessment. Two weeks after the intervention, the average number of indoor resting female Ae. aegypti per house in the intervention villages had declined approximately three-fold, whereas in the controls there was only a slight reduction (16%). The magnitude of the difference between the two areas diminished over time, which contact bioassays confirmed was likely due to a gradual reduction of insecticidal effect of the jar covers. In the study area, insecticide-treated covers for large concrete water storage jars were efficacious for controlling Ae. aegypti in the protected water jars and with a demonstrable effect on adult densities and survival. Further studies of this targeted container strategy in Cambodia, and elsewhere, are recommended. However, improvements in technology that would extend the duration of insecticidal effectiveness of LN materials may be needed for the development of cost-effective public health applications. PMID:19263854

  11. Community-wide distribution of long-lasting insecticidal nets can halt transmission of lymphatic filariasis in southeastern Nigeria.

    PubMed

    Richards, Frank O; Emukah, Emmanuel; Graves, Patricia M; Nkwocha, Omeni; Nwankwo, Lawrence; Rakers, Lindsay; Mosher, Aryc; Patterson, Amy; Ozaki, Masayo; Nwoke, Bertram E B; Ukaga, Chinyere N; Njoku, Chidiebere; Nwodu, Kenrick; Obasi, Andrew; Miri, Emmanuel S

    2013-09-01

    Lymphatic filariasis (LF) in rural southeastern Nigeria is transmitted mainly by Anopheles spp. mosquitoes. Potential coinfection with Loa loa in this area has prevented use of ivermectin in the mass drug administration (MDA) strategy for LF elimination because of potential severe adverse L. loa-related reactions. This study determined if long-lasting insecticidal net (LLIN) distribution programs for malaria would interrupt LF transmission in such areas, without need for MDA. Monthly entomologic monitoring was conducted in sentinel villages before and after LLIN distribution to all households and all age groups (full coverage) in two districts, and to pregnant women and children less than five years of age in the other two districts. No change in human LF microfilaremia prevalence was observed, but mosquito studies showed a statistically significant decrease in LF infection and infectivity with full-coverage LLIN distribution. We conclude that LF transmission can be halted in southeastern Nigeria by full-coverage LLIN distribution, without MDA. PMID:23939708

  12. Community-Wide Distribution of Long-Lasting Insecticidal Nets Can Halt Transmission of Lymphatic Filariasis in Southeastern Nigeria

    PubMed Central

    Richards, Frank O.; Emukah, Emmanuel; Graves, Patricia M.; Nkwocha, Omeni; Nwankwo, Lawrence; Rakers, Lindsay; Mosher, Aryc; Patterson, Amy; Ozaki, Masayo; Nwoke, Bertram E. B.; Ukaga, Chinyere N.; Njoku, Chidiebere; Nwodu, Kenrick; Obasi, Andrew; Miri, Emmanuel S.

    2013-01-01

    Lymphatic filariasis (LF) in rural southeastern Nigeria is transmitted mainly by Anopheles spp. mosquitoes. Potential coinfection with Loa loa in this area has prevented use of ivermectin in the mass drug administration (MDA) strategy for LF elimination because of potential severe adverse L. loa-related reactions. This study determined if long-lasting insecticidal net (LLIN) distribution programs for malaria would interrupt LF transmission in such areas, without need for MDA. Monthly entomologic monitoring was conducted in sentinel villages before and after LLIN distribution to all households and all age groups (full coverage) in two districts, and to pregnant women and children less than five years of age in the other two districts. No change in human LF microfilaremia prevalence was observed, but mosquito studies showed a statistically significant decrease in LF infection and infectivity with full-coverage LLIN distribution. We conclude that LF transmission can be halted in southeastern Nigeria by full-coverage LLIN distribution, without MDA. PMID:23939708

  13. Cost and cost effectiveness of long-lasting insecticide-treated bed nets - a model-based analysis

    PubMed Central

    2012-01-01

    Background The World Health Organization recommends that national malaria programmes universally distribute long-lasting insecticide-treated bed nets (LLINs). LLINs provide effective insecticide protection for at least three years while conventional nets must be retreated every 6-12 months. LLINs may also promise longer physical durability (lifespan), but at a higher unit price. No prospective data currently available is sufficient to calculate the comparative cost effectiveness of different net types. We thus constructed a model to explore the cost effectiveness of LLINs, asking how a longer lifespan affects the relative cost effectiveness of nets, and if, when and why LLINs might be preferred to conventional insecticide-treated nets. An innovation of our model is that we also considered the replenishment need i.e. loss of nets over time. Methods We modelled the choice of net over a 10-year period to facilitate the comparison of nets with different lifespan (and/or price) and replenishment need over time. Our base case represents a large-scale programme which achieves high coverage and usage throughout the population by distributing either LLINs or conventional nets through existing health services, and retreats a large proportion of conventional nets regularly at low cost. We identified the determinants of bed net programme cost effectiveness and parameter values for usage rate, delivery and retreatment cost from the literature. One-way sensitivity analysis was conducted to explicitly compare the differential effect of changing parameters such as price, lifespan, usage and replenishment need. Results If conventional and long-lasting bed nets have the same physical lifespan (3 years), LLINs are more cost effective unless they are priced at more than USD 1.5 above the price of conventional nets. Because a longer lifespan brings delivery cost savings, each one year increase in lifespan can be accompanied by a USD 1 or more increase in price without the cheaper net

  14. Challenges for malaria elimination in Zanzibar: pyrethroid resistance in malaria vectors and poor performance of long-lasting insecticide nets

    PubMed Central

    2013-01-01

    Background Long-lasting insecticide treated nets (LLINs) and indoor residual house spraying (IRS) are the main interventions for the control of malaria vectors in Zanzibar. The aim of the present study was to assess the susceptibility status of malaria vectors against the insecticides used for LLINs and IRS and to determine the durability and efficacy of LLINs on the island. Methods Mosquitoes were sampled from Pemba and Unguja islands in 2010–2011 for use in WHO susceptibility tests. One hundred and fifty LLINs were collected from households on Unguja, their physical state was recorded and then tested for efficacy as well as total insecticide content. Results Species identification revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a small number of An. gambiae s.s. and An. merus being present. Susceptibility tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible to all pyrethroids tested. A physical examination of 150 LLINs showed that two thirds were damaged after only three years in use. All used nets had a significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2 compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly against both susceptible An. gambiae s.s. colony mosquitoes and wild-type mosquitoes from Pemba after just six washes (p < 0.001). Conclusion The sustainability of the gains achieved in malaria control in Zanzibar is seriously threatened by the resistance of malaria vectors to pyrethroids and the short-lived efficacy of LLINs. This study has revealed that even in relatively well-resourced and logistically manageable places like Zanzibar, malaria elimination is going to be difficult to achieve with the current control measures. PMID:23537463

  15. Laboratory and experimental hut evaluation of a long-lasting insecticide treated blanket for protection against mosquitoes

    PubMed Central

    2014-01-01

    Background Long-lasting insecticide treated blankets (LLIBs) may provide additional protection against malaria where use of long lasting insecticidal nets (LLIN) is low or impractical such as in disaster or emergency situations. Methods Initial efficacy testing of a new candidate LLIB was carried out at LSHTM and KCMUCo, before and after washing, in cone and ball bioassays and arm-in-cage tests against pyrethroid susceptible Anopheles gambiae. A small scale field trial was conducted using veranda-trap experimental huts in northern Tanzania against wild An. arabiensis and Culex quinquefasciatus mosquitoes. Treatments included unwashed and 5 times washed permethrin treated LLIB and blankets hand-treated with permethrin (ITB), untreated blankets, and a holed unwashed Olyset net. Results Cone test mortality was 75% for LLIB when unwashed, but decreased to 32% after 5 washes and <10% after 10 washes. In arm-in-cage tests protection against biting was 100% for LLIBs regardless of the number of washes while reduction in landings was 79% when unwashed, 75% after 5 washes, but declined to 41% after 10 and 33% after 20 washes. In ball bioassays using pyrethroid resistant An. arabiensis, mortality was low in all treatments (<35%) and there was no significant difference in mortality between Olyset net, LLIB or ITB (p > 0.05). Percentage mortality of An. arabiensis in huts with LLIB unwashed (26%) was not statistically different to Olyset net (31%, p = 0.5). The 5 times washed LLIB reduced blood-feeding by 49% which was equivalent to Olyset net (p > 0.086). There was no significant difference in percentage blood-feeding between LLIB and ITB unwashed or 5 times washed (p = 0.147 and p = 0.346 respectively). The 5 times washed LLIB reduced blood-feeding of Culex quinquefasciatus by 40%, although the Olyset provided the greatest protection with 85% inhibition. ELISA analysis of a sub-sample of blood fed mosquitoes showed that not all had fed on humans in the

  16. Malaria knowledge and long-lasting insecticidal net use in rural communities of central Côte d'Ivoire

    PubMed Central

    2011-01-01

    Background To improve effectiveness of malaria control interventions, it is essential to deepen the knowledge of contextual factors that govern people's practice for preventive and curative measures. The aim of this study was to determine factors that influence the use of long-lasting insecticidal nets (LLINs) in three rural communities of Côte d'Ivoire, two of which benefited from recent interventions. Methods The study was carried out in 957 households in three villages (Bozi, N'Dakonankro and Yoho) located in central Côte d'Ivoire. Indicators of socioeconomic position (SEP), malaria knowledge and practice, placing special emphasis on LLINs, were investigated during a cross-sectional questionnaire survey. Principal component analysis was used to calculate the SEP of households by means of a list of household assets ownership. The concentration index was used to assess the direction of the association between SEP and a given variable. To compare groups or means, Fisher's exact test, χ2 and Kruskal-Wallis test were used, as appropriate. Results Significant differences were found between SEP and reported malaria symptoms, such as fever or hot body, convulsion, anaemia and jaundice (yellow eyes). Individuals from the least poor group cited more often the use of bed nets and insecticide-treated nets (ITNs) compared to poorer groups. The mean number of individuals reporting the use of bed nets and LLINs was different between groups with different educational level. Moreover, the mean number of LLINs in a household was influenced by the presence of children below five years of age. Conclusion The study not only confirmed that education and SEP play important roles in the prevention and control of malaria and promotion of health in general, but pointed at the basic essential knowledge and the key behavioural elements that should guide education and learning processes among the poorer segments of the population. In turn, such knowledge may change behaviour and lead to

  17. Shift in species composition in the Anopheles gambiae complex after implementation of long-lasting insecticidal nets in Dielmo, Senegal.

    PubMed

    Sougoufara, S; Harry, M; Doucouré, S; Sembène, P M; Sokhna, C

    2016-09-01

    Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the cornerstones of malaria vector control. However, the effectiveness of these control tools depends on vector ecology and behaviour, which also largely determine the efficacy of certain Anopheles mosquitoes (Diptera: Culicidae) as vectors. Malaria vectors in sub-Saharan Africa are primarily species of the Anopheles gambiae complex, which present intraspecific differences in behaviour that affect how they respond to vector control tools. The focus of this study is the change in species composition in the An. gambiae complex after the implementation of LLINs in Dielmo, Senegal. The main findings referred to dramatic decreases in the proportions of Anopheles coluzzii and An. gambiae after the introduction of LLINs, and an increase in the proportion of Anopheles arabiensis. Two years after LLINs were first introduced, An. arabiensis remained the most prevalent species and An. gambiae had begun to rebound. This indicated a need to develop additional vector control tools that can target the full range of malaria vectors. PMID:27058993

  18. Bio-efficacy of selected long-lasting insecticidal nets against pyrethroid resistant Anopheles arabiensis from South-Western Ethiopia

    PubMed Central

    2012-01-01

    Background The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae s.s. and Anopheles arabiensis may compromise control initiatives based on insecticide-treated nets (ITNs) or indoor residual spraying (IRS), and thus threaten the global malaria elimination strategy. Methods We investigated pyrethroid resistance in four populations of An. arabiensis from south-western Ethiopia and then assessed the bio-efficacy of six World Health Organization recommended long lasting insecticidal nets (LLINs) using these populations. Results For all four populations of An. arabiensis, bottle bioassays indicated low to moderate susceptibility to deltamethrin (mortality at 30 minutes ranged between 43 and 80%) and permethrin (mortality ranged between 16 and 76%). Pre-exposure to the synergist piperonylbutoxide (PBO) significantly increased the susceptibility of all four populations to both deltamethrin (mortality increased between 15.3 and 56.8%) and permethrin (mortality increased between 11.6 and 58.1%), indicating the possible involvement of metabolic resistance in addition to the previously identified kdr mutations. There was reduced susceptibility of all four An. arabiensis populations to the five standard LLINs tested (maximum mortality 81.1%; minimum mortality 13.9%). Bio-efficacy against the four populations varied by net type, with the largest margin of difference observed with the Jimma population (67.2% difference). Moreover, there were differences in the bio-efficacy of each individual standard LLIN against the four mosquito populations; for example there was a difference of 40% in mortality of Yorkool against two populations. Results from standard LLINs indicated reduced susceptibility to new, unused nets that was likely due to observed pyrethroid resistance. The roof of the combination LLIN performed optimally (100% mortality) against all the four populations of An. arabiensis, indicating that observed reductions in

  19. A tracking tool for long-lasting insecticidal (mosquito) net intervention following a 2011 national distribution in Benin

    PubMed Central

    2014-01-01

    Background Following a mass distribution of long-lasting insecticidal nets (LLINs) in Benin, we used WHO guidelines to develop an assessment tool which is described in this report. It involved assessment of the three WHO indicators: survivorship, integrity and bio-efficacy. Methods To evaluate the assessment tool, we selected four communities, two in the Southern part of the country, and two in the North. One of the two assessment communities in each geographic setting had ready access to water and a higher reported frequency of washing LLINs. It was assumed that nets in communities with greater washing frequencies would show greater loss of durability. If the tool was sensitive enough to detect such differences, the field testing would confirm its suitability for general use in different settings in Benin. While durability indicators of survival and fabric integrity were quantified using standard WHO methodology, bio-efficacy was assessed using a ‘new’ alternative (to the WHO bioassay test), involving gas chromatography. Additionally, data management used current internet technology for ‘real time’ analysis at a central monitoring location. Results While no difference in survivorship was observed between sites with ready access to water for washing, both in the North and the South, there was a significant difference in integrity. In the South and in the North, nets from sites near water (Kessounou and Malanville) showed greater damage to integrity than did the nets from Allada and Kandi (sites far from water). As expected, LLIN integrity was significantly lower when a community was near water (p < 0.01). Bio-efficacy measurements, based on GC, were found to be so variable. Conclusion A rapid decrease of the LLINs fabric integrity was observed in areas near water for washing following the first 6 months post-distribution. Due to the way that the insecticide is incorporated into the LLIN fiber and its migration to the surface, confounding results were

  20. Impact of operational effectiveness of long-lasting insecticidal nets (LLINs) on malaria transmission in pyrethroid-resistant areas

    PubMed Central

    2013-01-01

    Background A dynamic study on the transmission of malaria was conducted in two areas (R+ area: Low resistance area; R+++ area: High resistance area) in the department of Plateau in South Eastern Benin, where the population is protected by Long Lasting Insecticidal Nets (LLINs). The aim of this study was to determine if the resistance of malaria vectors to insecticides has an impact on their behavior and on the effectiveness of LLINs in the reduction of malaria transmission. Methods Populations of Anopheles gambiae s.l. were sampled monthly by human landing catch in the two areas to evaluate human biting rates (HBR). Collected mosquitoes were identified morphologically and female Anopheles mosquitoes were tested for the presence of Plasmodium falciparum antigen as assessed using ELISA. The entomological inoculation rate (EIR) was also calculated (EIR = HBR x sporozoitic index [S]). We estimated the parity rate by dissecting the females of An. gambiae. Finally, window catch and spray catch were conducted in order to assess the blood feeding rate and the exophily rate of vectors. Results After 6 months of tracking the mosquito's behavior in contact with the LLINs (Olyset) in R+++ and R+ areas, the entomological indicators of the transmission of malaria (parity rate and sporozoitic index) were similar in the two areas. Also, An. gambiae populations showed the same susceptibility to P. falciparum in both R+ and R+++ areas. The EIR and the exophily rate are higher in R+ area than in R+++ area. But the blood-feeding rate is lower in R+ area comparing to R+++. Conclusion The highest entomological inoculation rate observed in R+ area is mostly due to the strong aggressive density of An. gambiae recorded in one of the study localities. On the other hand, the highest exophily rate and the low blood-feeding rate recorded in R+ area compared to R+++ area are not due to the resistance status of An. gambiae, but due to the differences in distribution and availability of

  1. [Operation to promote use of long-lasting insecticidal nets (LLIN) in French Guiana in 2006: design, implementation and results].

    PubMed

    Mansotte, F; Ravachol, F; Carlisi, R; Caudal, J; Pinchon, S; Maison, D

    2010-06-01

    In 2006, the Regional Health Office (DSDS) in French Guiana undertook a major operation involving importation and distribution of long-lasting insecticide treated nets (LLIN/ITN). In collaboration with the WHO, a Vietnamese manufacturer of LLINs suited to the requirements of French Guiana was sourced. With the help of a dynamic local importer and dealer, a sales network was developed through chemist shops located all over French Guiana. This network provided wide coverage since these outlets can be found in all large communities. The selling price ranged from 15 to 23 euros depending on the model, i.e., hammock or bed size. In addition, LLINs were distributed within the framework of two special programs. First they are given to women giving birth in French Guiana and undergoing medical surveillance as part of the Mother and Child Protection program by public healthcare system. Second they are distributed in case of natural disaster or other events that could lead to an increased risk of vector-borne outbreaks. Thanks to this operation, a total of 13,882 LLINs were delivered in French Guiana from July 2006 to December 2008. This milestone operation in the fight against malaria was made possible thanks to funding granted on a one-time basis after the outbreak of dengue in 2005-2006. The structure of this operation and its survival will depend on the continued goodwill and determination of a small group of local partners who created this successful distribution campaign with no specific guidance or program from the national authorities. PMID:20734592

  2. Analysing and recommending options for maintaining universal coverage with long-lasting insecticidal nets: the case of Tanzania in 2011

    PubMed Central

    2013-01-01

    Background Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or “Keep-Up” distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Methods Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. Results LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of $449 million USD and ensure

  3. Efficacy of Olyset® Plus, a New Long-Lasting Insecticidal Net Incorporating Permethrin and Piperonil-Butoxide against Multi-Resistant Malaria Vectors

    PubMed Central

    Pennetier, Cédric; Bouraima, Aziz; Chandre, Fabrice; Piameu, Michael; Etang, Josiane; Rossignol, Marie; Sidick, Ibrahim; Zogo, Barnabas; Lacroix, Marie-Noëlle; Yadav, Rajpal; Pigeon, Olivier; Corbel1, Vincent

    2013-01-01

    Due to the rapid extension of pyrethroid resistance in malaria vectors worldwide, manufacturers are developing new vector control tools including insecticide mixtures containing at least two active ingredients with different mode of action as part of insecticide resistance management. Olyset® Plus is a new long-lasting insecticidal net (LLIN) incorporating permethrin and a synergist, piperonyl butoxide (PBO), into its fibres in order to counteract metabolic-based pyrethroid resistance of mosquitoes. In this study, we evaluated the efficacy of Olyset® Plus both in laboratory and field against susceptible and multi-resistant malaria vectors and compared with Olyset Net, which is a permethrin incorporated into polyethylene net. In laboratory, Olyset® Plus performed better than Olyset® Net against susceptible Anopheles gambiae strain with a 2-day regeneration time owing to an improved permethrin bleeding rate with the new incorporation technology. It also performed better than Olyset® Net against multiple resistant populations of An. gambiae in experimental hut trials in West Africa. Moreover, the present study showed evidence for a benefit of incorporating a synergist, PBO, with a pyrethroid insecticide into mosquito netting. These results need to be further validated in a large-scale field trial to assess the durability and acceptability of this new tool for malaria vector control. PMID:24116029

  4. DDT and pyrethroid resistance status and laboratory evaluation of bio-efficacy of long lasting insecticide treated nets against Culex quinquefasciatus and Culex decens in Ghana.

    PubMed

    Kudom, Andreas A; Mensah, Ben A; Froeschl, Guenter; Rinder, Heinz; Boakye, Daniel

    2015-10-01

    Nuisance from Culex mosquitoes in Ghana has a serious negative impact on the standard of living in many urban communities. In addition, a perceived lack of efficacy of long lasting insecticide treated nets (LLINs) against nuisance mosquitoes contributes to their discontinued use. This again compromises malaria control, even if Anopheles species themselves would still be susceptible to the insecticides used. Control strategies involve pyrethroid insecticides but information on Culex mosquito susceptibility to these insecticides is limited. A nationwide survey was conducted to address this problem. In adults, susceptibility to permethrin, deltamethrin and DDT as well as enzyme activity and kdr mutation were determined. Cone and tunnel bioassay were also carried out to determine the efficacy of LLINs against the mosquitoes. Culex quinquefasciatus and Culex decens were identified in the study area. Higher deltamethrin and DDT resistance and relatively low permethrin resistance were observed in both species. High enzyme activities and kdr mutations were observed in C. quinquefasciatus but not in C. decens. However, reduced efficacy of LLINs was observed in both mosquito species. This adds up to the evidence of the spread of pyrethroid resistance in mosquitoes and its negative impact on control strategies. PMID:26215129

  5. A qualitative study on the acceptability and preference of three types of long-lasting insecticide-treated bed nets in Solomon Islands: implications for malaria elimination

    PubMed Central

    Atkinson, Jo-An; Bobogare, Albino; Fitzgerald, Lisa; Boaz, Leonard; Appleyard, Bridget; Toaliu, Hilson; Vallely, Andrew

    2009-01-01

    Background In March 2008, the Solomon Islands and Vanuatu governments raised the goal of their National Malaria Programmes from control to elimination. Vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal bed nets (LLINs) are key integral components of this programme. Compliance with these interventions is dependent on their acceptability and on the socio-cultural context of the local population. These factors need to be investigated locally prior to programme implementation. Method Twelve focus group discussions (FGDs) were carried out in Malaita and Temotu Provinces, Solomon Islands in 2008. These discussions explored user perceptions of acceptability and preference for three brands of long-lasting insecticide-treated bed nets (LLINs) and identified a number of barriers to their proper and consistent use. Results Mosquito nuisance and perceived threat of malaria were the main determinants of bed net use. Knowledge of malaria and the means to prevent it were not sufficient to guarantee compliance with LLIN use. Factors such as climate, work and evening social activities impact on the use of bed nets, particularly in men. LLIN acceptability plays a varying role in compliance with their use in villages involved in this study. Participants in areas of reported high and year round mosquito nuisance and perceived threat of malaria reported LLIN use regardless of any reported unfavourable characteristics. Those in areas of low or seasonal mosquito nuisance were more likely to describe the unfavourable characteristics of LLINs as reasons for their intermittent or non-compliance. The main criterion for LLIN brand acceptability was effectiveness in preventing mosquito bites and malaria. Discussions highlighted considerable confusion around LLIN care and washing which may be impacting on their effectiveness and reducing their acceptability in Solomon Islands. Conclusion Providing LLINs that are acceptable will be more important for

  6. Wash durability and optimal drying regimen of four brands of long-lasting insecticide-treated nets after repeated washing under tropical conditions

    PubMed Central

    2010-01-01

    Background The current study was undertaken to determine the optimal wash-drying regimen and the effects of different washing procedures on the efficacy, and durability of four brands of newly introduced long-lasting insecticide-treated nets (LLINs) under tropical conditions. Methods In the current study, the following four LLINs were tested: Olyset®, PermaNet ®2.0, BASF® and TNT®. Nets were divided into three sets; one set was washed by hand rubbing and air-dried either hanging or spread on the ground in direct sunlight or hanging or spread on the ground under the shade. A second set was washed using the WHO protocol (machine) and the third set was washed by beating the nets on rocks. The biological activities of the nets were assessed by a three-minute bioassay cone test and the residual insecticide contents were determined using high performance liquid chromatography (HPLC) procedure. Results Nets that were dried hanging under the shade retained more insecticide, 62.5% and recorded higher mortality compared to nets which were dried lying on the ground in direct sunlight 58.8%, nets dried under the shade spread on the ground 56.3%, and 57.8% for nets dried hanging in direct sunlight. It was also observed that nets washed by the standard WHO protocol, retained more insecticide and were more effective in killing mosquitoes compared to nets washed by local methods of hand rubbing and beating on rocks. There were significant differences between drying regimens (p < 0.0001) and between washing procedures (p < 0.001) respectively. However, the effect of net type was statistically insignificant. The statistical differences on individual nets were also compared, for PermaNet® and TNT there were no significant differences observed between the four drying regimens (p = 0.7944 and 0.4703) respectively). For BASF and Olyset, the differences were significant (p < 0.001 and p > 0.0001). Conclusion The results of this study suggest that washing and drying regimen influence

  7. Factors Associated with Sustained Use of Long-Lasting Insecticide-Treated Nets Following a Reduction in Malaria Transmission in Southern Zambia.

    PubMed

    Pinchoff, Jessie; Hamapumbu, Harry; Kobayashi, Tamaki; Simubali, Limonty; Stevenson, Jennifer C; Norris, Douglas E; Colantuoni, Elizabeth; Thuma, Philip E; Moss, William J

    2015-11-01

    Understanding factors influencing sustained use of long-lasting insecticide-treated nets (LLIN) in areas of declining malaria transmission is critical to sustaining control and may facilitate elimination. From 2008 to 2013, 655 households in Choma District, Zambia, were randomly selected and residents were administered a questionnaire and malaria rapid diagnostic test. Mosquitoes were collected concurrently by light trap. In a multilevel model, children and adolescents of 5-17 years of age were 55% less likely to sleep under LLIN than adults (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.35, 0.58). LLIN use was 80% higher during the rainy season (OR = 1.8; CI = 1.5, 2.2) and residents of households with three or more nets were over twice as likely to use a LLIN (OR = 2.1; CI = 1.4, 3.1). For every increase in 0.5 km from the nearest health center, the odds of LLIN use decreased 9% (OR = 0.9; CI = 0.88, 0.98). In a second multilevel model, the odds of LLIN use were more than twice high if more than five mosquitoes (anopheline and culicine) were captured in the house compared with households with no mosquitoes captured (OR = 2.1; CI = 1.1, 3.9). LLIN use can be sustained in low-transmission settings with continued education and distributions, and may be partially driven by the presence of nuisance mosquitoes. PMID:26324729

  8. Evaluation of different mesh sizes of long lasting insecticidal nets against Phlebotomus argentipes Annandale and Brunetti (Diptera: Psychodidae), in Bihar state of India.

    PubMed

    Singh, Ram; Kumar, Pramod

    2016-07-01

    The study present result of long lasting insecticidal nets (LLINs) of different mesh sizes viz. PermaNet(R) 156mesh/inch(2), PermaNet(R) 196mesh/inch(2), PermaNet(R) 196mesh/inch2+75cm border of fine cloth in reducing Phlebotomus argentipes population along with community acceptance in three intervention villages. Entire experimental period of treatments maximum reduction 93.67% was observed in PermaNet(R) 196mesh/inch(2)+75cm border followed by PermaNet(R) 196mesh/inch(2) 91.90 and 74.29% in PermaNet(R)156mesh/inch(2), when compared to control all the LLINs were showed significant reduction of P. argentipes population while compare to between them there was no significant difference. The significant reduction in gravid P. argentipes, was recorded as 71.87, 87.92 and 91.27%, in PermaNet(R) 156mesh/inch(2), PermaNet(R) 196mesh/inch(2) and PermaNet(R) 196mesh/inch(2)+75cm, respectively. The preference was high for PermaNet(R) 156mesh/inch(2) without any side effect of LLINs. PMID:27016015

  9. Long-lasting insecticide-treated house screens and targeted treatment of productive breeding-sites for dengue vector control in Acapulco, Mexico

    PubMed Central

    Che-Mendoza, Azael; Guillermo-May, Guillermo; Herrera-Bojórquez, Josué; Barrera-Pérez, Mario; Dzul-Manzanilla, Felipe; Gutierrez-Castro, Cipriano; Arredondo-Jiménez, Juan I.; Sánchez-Tejeda, Gustavo; Vazquez-Prokopec, Gonzalo; Ranson, Hilary; Lenhart, Audrey; Sommerfeld, Johannes; McCall, Philip J.; Kroeger, Axel; Manrique-Saide, Pablo

    2015-01-01

    Background Long-lasting insecticidal net screens (LLIS) fitted to domestic windows and doors in combination with targeted treatment (TT) of the most productive Aedes aegypti breeding sites were evaluated for their impact on dengue vector indices in a cluster-randomised trial in Mexico between 2011 and 2013. Methods Sequentially over 2 years, LLIS and TT were deployed in 10 treatment clusters (100 houses/cluster) and followed up over 24 months. Cross-sectional surveys quantified infestations of adult mosquitoes, immature stages at baseline (pre-intervention) and in four post-intervention samples at 6-monthly intervals. Identical surveys were carried out in 10 control clusters that received no treatment. Results LLIS clusters had significantly lower infestations compared to control clusters at 5 and 12 months after installation, as measured by adult (male and female) and pupal-based vector indices. After addition of TT to the intervention houses in intervention clusters, indices remained significantly lower in the treated clusters until 18 (immature and adult stage indices) and 24 months (adult indices only) post-intervention. Conclusions These safe, simple affordable vector control tools were well-accepted by study participants and are potentially suitable in many regions at risk from dengue worldwide. PMID:25604761

  10. School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania.

    PubMed

    Lalji, Shabbir; Ngondi, Jeremiah M; Thawer, Narjis G; Tembo, Autman; Mandike, Renata; Mohamed, Ally; Chacky, Frank; Mwalimu, Charles D; Greer, George; Kaspar, Naomi; Kramer, Karen; Mlay, Bertha; Issa, Kheri; Lweikiza, Jane; Mutafungwa, Anold; Nzowa, Mary; Willilo, Ritha A; Nyoni, Waziri; Dadi, David; Ramsan, Mahdi M; Reithinger, Richard; Magesa, Stephen M

    2016-06-20

    Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country's Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania. PMID:27353618

  11. School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania

    PubMed Central

    Lalji, Shabbir; Ngondi, Jeremiah M; Thawer, Narjis G; Tembo, Autman; Mandike, Renata; Mohamed, Ally; Chacky, Frank; Mwalimu, Charles D; Greer, George; Kaspar, Naomi; Kramer, Karen; Mlay, Bertha; Issa, Kheri; Lweikiza, Jane; Mutafungwa, Anold; Nzowa, Mary; Willilo, Ritha A; Nyoni, Waziri; Dadi, David; Ramsan, Mahdi M; Reithinger, Richard; Magesa, Stephen M

    2016-01-01

    ABSTRACT Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country’s Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania. PMID:27353618

  12. Effectiveness and feasibility of long-lasting insecticide-treated curtains and water container covers for dengue vector control in Colombia: a cluster randomised trial

    PubMed Central

    Quintero, Juliana; García-Betancourt, Tatiana; Cortés, Sebastian; García, Diana; Alcalá, Lucas; González-Uribe, Catalina; Brochero, Helena; Carrasquilla, Gabriel

    2015-01-01

    Background Long-lasting insecticide-treated net (LLIN) window and door curtains alone or in combination with LLIN water container covers were analysed regarding effectiveness in reducing dengue vector density, and feasibility of the intervention. Methods A cluster randomised trial was conducted in an urban area of Colombia comparing 10 randomly selected control and 10 intervention clusters. In control clusters, routine vector control activities were performed. The intervention delivered first, LLIN curtains (from July to August 2013) and secondly, water container covers (from October to March 2014). Cross-sectional entomological surveys were carried out at baseline (February 2013 to June 2013), 9 weeks after the first intervention (August to October 2013), and 4–6 weeks after the second intervention (March to April 2014). Results Curtains were installed in 922 households and water container covers in 303 households. The Breteau index (BI) fell from 14 to 6 in the intervention group and from 8 to 5 in the control group. The additional intervention with LLIN covers for water containers showed a significant reduction in pupae per person index (PPI) (p=0.01). In the intervention group, the PPI index showed a clear decline of 71% compared with 25% in the control group. Costs were high but options for cost savings were identified. Conclusions Short term impact evaluation indicates that the intervention package can reduce dengue vector density but sustained effect will depend on multiple factors. PMID:25604762

  13. The Effect of Long Lasting Insecticide Bed Net Use on Malaria Prevalence in the Tombel Health District, South West Region-Cameroon

    PubMed Central

    Dzi, Kevin T. J.; Ngimuh, Leonard; Enyong, Peter

    2016-01-01

    Malaria remains a major public health problem in Africa, and its prevalence in Cameroon stands at 29%. Long Lasting Insecticide Nets (LLINs) were distributed in 2011 to reduce malaria mortality and morbidity; however, assessment of this intervention is scanty. The present study in the Tombel health district (THD) investigated the impact of this distribution on malaria prevalence. A total of 31,657 hospital records from 3 health facilities in 3 health areas for 2010–2013 were examined. Records for 2010 and 2011 provided predistribution baseline data, while those of 2012 and 2013 represented postdistribution data. 8,679 (27.4%) patients were positive for malaria. Children below 5 years had the highest prevalence (40.7%). The number of confirmed cases was highest from June to August (peak rainy season). Malaria prevalence was higher in males (25.3%) than in females (23.2%). Malaria prevalence increased in THD from 26.7% in 2010 to 30.7% in 2011 but dropped to 22.7% in 2012 and then increased in 2013 to 29.5%. There was an overall drop in the total number of confirmed malaria cases in 2012; this decrease was significant in Ebonji (p < 0.001) and Nyasoso (p < 0.015) health areas. The distribution of LLINs led to a short lived reduction in malaria prevalence in THD. LLIN distribution and other control activities should be reinforced to keep malaria prevalence low especially among the 0–5-year group. PMID:27403371

  14. Pilot study on the combination of an organophosphate-based insecticide paint and pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors in Burkina Faso.

    PubMed

    Mosqueira, Beatriz; Soma, Dieudonné D; Namountougou, Moussa; Poda, Serge; Diabaté, Abdoulaye; Ali, Ouari; Fournet, Florence; Baldet, Thierry; Carnevale, Pierre; Dabiré, Roch K; Mas-Coma, Santiago

    2015-08-01

    A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical

  15. A phase III trial to evaluate the efficacy, fabric integrity and community acceptance of Netprotect® using a recommended long-lasting insecticidal net as positive control

    PubMed Central

    2014-01-01

    Background The evaluation of new long-lasting insecticidal bed nets (LLINs) is coordinated by the WHO Pesticide Evaluation Scheme (WHOPES). In 2007, Netprotect® was granted WHOPES interim recommendation after Phase I and II evaluations. Present study evaluates Netprotect® in a Phase III trial in rural Cambodia. Methods A randomized, prospective longitudinal study design was used to assess the performance of Netprotect® over a period of three years, using conventionally-treated nets and a WHOPES recommended LLIN (PermaNet® 2.0) as positive controls. The primary outcomes were the physical integrity, insecticide content and cone bioassay performance using. Results The baseline deltamethrin concentration of 43% of Netprotect® nets were below the tolerance limit while 27% of PermaNet® 2.0 nets were above the target dose limits. By 36 months Netprotect® retained 35% while PermaNet® 2.0 retained 49% of baseline insecticide dose. Moreover the proportion of the inactive deltamethrin R-alpha isomer in the Netprotect® nets was 33% at the baseline and increased to 69% after three years while it was low and almost constant for PermaNet® 2.0 (3-7%). Only 71% of Netprotect® met the WHO criteria for bio-efficacy after three years while at least 80% is required. Moreover Netprotect® nets failed for the WHOPES criteria after 12 and 24 months. The reference LLIN met the WHOPES criteria throughout the study. Over the entire three years the reference LLIN did obtain significant higher mosquito mortality than Netprotect®. The physical integrity was based on the proportionate hole index and after three years, 25% of Netprotect® and 30% of PermaNet® 2.0 were in a mediocre or poor state. Conclusion Netprotect® did not meet the minimum WHO criteria for bio-efficacy after 12, 24 and 36 months. The use of a reference LLIN as positive control was helpful for data interpretation. However, for future three-year studies, it is essential that before initiating any study nets

  16. Success of Senegal's first nationwide distribution of long-lasting insecticide-treated nets to children under five - contribution toward universal coverage

    PubMed Central

    2011-01-01

    Background In 2009, the first national long-lasting insecticide-treated net (LLIN) distribution campaign in Senegal resulted in the distribution of 2.2 million LLINs in two phases to children aged 6-59 months. Door-to-door teams visited all households to administer vitamin A and mebendazole, and to give a coupon to redeem later for an LLIN. Methods A nationwide community-based two-stage cluster survey was conducted, with clusters selected within regions by probability proportional to size sampling, followed by GPS-assisted mapping, simple random selection of households in each cluster, and administration of a questionnaire using personal digital assistants (PDAs). The questionnaire followed the Malaria Indicator Survey format, with rosters of household members and bed nets, and questions on campaign participation. Results There were 3,280 households in 112 clusters representing 33,993 people. Most (92.1%) guardians of eligible children had heard about the campaign, the primary sources being health workers (33.7%), neighbours (26.2%), and radio (22.0%). Of eligible children, 82.4% received mebendazole, 83.8% received vitamin A, and 75.4% received LLINs. Almost all (91.4%) LLINs received during the campaign remained in the household; of those not remaining, 74.4% had been given away and none were reported sold. At least one insecticide-treated net (ITN) was present in 82.3% of all households, 89.2% of households with a child < 5 years and 57.5% of households without a child < 5 years. Just over half (52.4%) of ITNs had been received during the campaign. Considering possible indicators of universal coverage, 39.8% of households owned at least one ITN per two people, 21.6% owned at least one ITN per sleeping space and 34.7% of the general population slept under an ITN the night before the survey. In addition, 45.6% of children < 5 years, and 49.2% of pregnant women had slept under an ITN. Conclusions The nationwide integrated LLIN distribution campaign allowed

  17. Bioefficacy of long-lasting insecticidal nets against pyrethroid-resistant populations of Anopheles gambiae s.s. from different malaria transmission zones in Uganda

    PubMed Central

    2013-01-01

    Background There are major concerns over sustaining the efficacy of current malaria vector control interventions given the rapid spread of resistance, particularly to pyrethroids. This study assessed the bioefficacy of five WHO-recommended long-lasting insecticidal nets (LLINs) against pyrethroid-resistant Anopheles gambiae field populations from Uganda. Methods Adult An. gambiae from Lira, Tororo, Wakiso and Kanungu districts were exposed to permethrin (0.75%) or deltamethrin (0.05%) in standard WHO susceptibility tests. Cone bioassays were used to measure the bioefficacy of four mono-treated LLINs (Olyset®, Interceptor®, Netprotect® and PermaNet® 2.0) and one combination LLIN (PermaNet® 3.0) against the four mosquito populations. Wireball assays were similarly conducted to determine knockdown rates. Species composition and kdr mutation frequency were determined for a sample of mosquitoes from each population. Chemical assays confirmed that test nets fell within target dose ranges. Results Anopheles gambiae s.s. predominated at all four sites (86 - 99% of Anopheles spp.) with moderate kdr L1014S allelic frequency (0.34 – 0.37). Confirmed or possible resistance to both permethrin and deltamethrin was identified for all four test populations. Reduced susceptibility to standard LLINs was observed for all four populations, with mortality rates as low as 45.8% even though the nets were unused. The combination LLIN PermaNet®3.0 showed the highest overall bioefficacy against all four An. gambiae s.l. populations (98.5 - 100% mortality). Wireball assays provided a more sensitive indicator of comparative bioefficacy, and PermaNet 3.0 was again associated with the highest bioefficacy against all four populations (76.5 – 91.7% mortality after 30 mins). Conclusions The bioefficacy of mono-treated LLINs against pyrethroid-resistant field populations of An. gambiae varied by LLIN type and mosquito population, indicating that certain LLINs may be more suitable than

  18. Design, implementation and evaluation of a national campaign to deliver 18 million free long-lasting insecticidal nets to uncovered sleeping spaces in Tanzania

    PubMed Central

    2013-01-01

    Background Since 2004, the Tanzanian National Voucher Scheme has increased availability and accessibility of insecticide-treated nets (ITNs) to pregnant women and infants by subsidizing the cost of nets purchased. From 2008 to 2010, a mass distribution campaign delivered nine million long-lasting insecticidal nets (LLINs) free-of-charge to children under-five years of age in Tanzania mainland. In 2010 and 2011, a Universal Coverage Campaign (UCC) led by the Ministry of Health and Social Welfare (MoHSW) was implemented to cover all sleeping spaces not yet reached through previous initiatives. Methods The UCC was coordinated through a unit within the National Malaria Control Programme. Partners were contracted by the MoHSW to implement different activities in collaboration with local government authorities. Volunteers registered the number of uncovered sleeping spaces in every household in the country. On this basis, LLINs were ordered and delivered to village level, where they were issued over a three-day period in each zone (three regions). Household surveys were conducted in seven districts immediately after the campaign to assess net ownership and use. Results The UCC was chiefly financed by the Global Fund to Fight AIDS, Tuberculosis and Malaria with important contributions from the US President’s Malaria Initiative. A total of 18.2 million LLINs were delivered at an average cost of USD 5.30 per LLIN. Overall, 83% of the expenses were used for LLIN procurement and delivery and 17% for campaign associated activities. Preliminary results of the latest Tanzania HIV Malaria Indicator Survey (2011–12) show that household ownership of at least one ITN increased to 91.5%. ITN use, among children under-five years of age, improved to 72.7% after the campaign. ITN ownership and use data post-campaign indicated high equity across wealth quintiles. Conclusion Close collaboration among the MoHSW, donors, contracted partners, local government authorities and volunteers

  19. Evidence of increasing Leu-Phe knockdown resistance mutation in Anopheles gambiae from Niger following a nationwide long-lasting insecticide-treated nets implementation

    PubMed Central

    Czeher, Cyrille; Labbo, Rabiou; Arzika, Ibrahim; Duchemin, Jean-Bernard

    2008-01-01

    Background At the end of 2005, a nationwide long-lasting insecticide-treated net (LLIN) distribution targeting the most vulnerable populations was implemented throughout Niger. A large number of studies in Africa have reported the existence of anopheline populations resistant to various insecticides, partly due to knockdown resistance (kdr) mutations, but few operational wide-scale control programmes were coupled with the monitoring of such mutations. The distribution of the kdr-west (kdr-w) Leu-Phe mutation was studied in Anopheles gambiae s.l. populations from Niger and temporal variations were monitored following the nationwide LLIN implementation. Methods Mosquitoes were collected from 14 localities during the wet seasons of 2005, 2006 and 2007 with additional sampling in the capital city, Niamey. After morphological identification of Anopheles gambiae s.l. specimens, DNA extracts were used for the determination of species and molecular forms of the Anopheles gambiae complex and for the detection of the kdr-w mutation. Results Around 1,500 specimens collected in the three consecutive years were analysed. All Anopheles arabiensis specimens analysed were homozygous susceptible, whereas the few Anopheles gambiae S forms exhibited a high overall kdr-w frequency. The M form samples exhibited a low overall kdr-w frequency before the LLIN distribution, that increased significantly in the two wet season collections following the LLIN distribution. Higher kdr frequencies were repeatedly noticed within host-seeking females compared to resting ones in indoor collections. In addition, preliminary results in M form urban populations from Niamey showed far higher kdr frequencies than in all of the rural sites studied. Discussion This study describes the first case of kdr mutation in Anopheles gambiae populations from Niger. It is suspected that the LLIN have caused the important temporal increase of kdr-w mutation observed during this study. While the kdr mutation is still

  20. How many mosquito nets are needed to achieve universal coverage? Recommendations for the quantification and allocation of long-lasting insecticidal nets for mass campaigns

    PubMed Central

    2010-01-01

    Background Long-lasting insecticidal nets are an effective tool for malaria prevention, and "universal coverage" with such nets is increasingly the goal of national malaria control programmes. However, national level campaigns in several countries have run out of nets in the course of distribution, indicating a problem in the method used to estimate the quantity needed. Presentation of hypothesis A major reason for the shortfall in estimation is the mismatch between the quantification factor used to plan procurement and the allocation algorithm used at community level, in particular the effect of needing to add an additional net to households with an odd number of inhabitants. To solve this problem a revised quantification factor is suggested. Testing hypothesis Based on data from a broad range of household surveys across Africa, the effect of odd-numbered households on numbers of nets distributed is estimated via two frequently used allocation methods. The impact of these algorithms on the proportion of households reaching a person to net ratio of 2:1, a frequently used marker of universal coverage is then calculated. Implications In order to avoid stock-outs of nets during national coverage campaigns, it is recommended to use a quantification factor of 1.78 people per net, with an additional allocation factor suggested to account for other common problems at the community level resulting in a final recommended ratio of 1.60 people per net. It is also recommend that community level allocation procedures be aligned with procurement estimates to reduce shortages of nets during campaign distributions. These analyses should enable programme managers to make evidence-based decisions and support a more efficient and effective use of LLIN distribution campaign resources. PMID:21087460

  1. Comparison of efficacy of five types of long-lasting insecticidal nets against Anopheles fluviatilis, the primary malaria vector in east-central India.

    PubMed

    Gunasekaran, K; Sahu, S S; Vijayakumar, T; Vaidyanathan, K; Yadav, R S; Pigeon, O; Jambulingam, P

    2014-07-01

    Five types of long-lasting insecticidal nets (LNs), namely, Olyset, Netprotect, PermaNet, DuraNet, and Interceptor, were tested after 20 washes for efficacy in terms of mortality, deterrence effect, blood-feeding inhibition, and induced exophily of the malaria vector Anopheles fluviatilis in experimental huts in Malkangiri district of Odisha State, India. Efficacy of the three synthetic pyrethroids (SPs) used in the LNs was also analyzed. Use of LNs reduced the entry of An. fluviatilis into the huts by 73.3-83.2%, and the five LNs were comparable in terms of deterrence. The exit rate of An. fluviatilis from the huts with untreated net was 56.3%, and relative to this, Olyset followed by DuraNet induced significantly a higher exophily. In contrast, the exit rate was significantly lower with Interceptor. Among the three SPs, permethrin induced significantly greater exophily relative to the untreated control, and as a result of this, permethrin-treated Olyset produced a lower mortality. Blood-feeding rate of An. fluviatilis was significantly lower with all the five LNs than the control. Similarly, all the three SPs significantly inhibited blood feeding compared with the control. Interceptor and DuraNet, both alphacypermethrin-treated LNs, caused relatively a higher mortality of An. fluviatilis than the other LNs. The five brands of LNs and three SPs tested in the current study were equally effective in terms of deterrence and blood-feeding inhibition; only exiting and killing effect differed among them. Permethrin-treated LNs induced greater exophily, while, overall, alphacypermethrin-treated LNs killed more An. fluviatilis that entered the huts. Advantage of deterrence, excito-repellent, and killing effects of LNs and appropriate selection of SP for net treatment are discussed in this paper. PMID:25118410

  2. Traditional Nets Interfere with the Uptake of Long-Lasting Insecticidal Nets in the Peruvian Amazon: The Relevance of Net Preference for Achieving High Coverage and Use

    PubMed Central

    Grietens, Koen Peeters; Muela Ribera, Joan; Soto, Veronica; Tenorio, Alex; Hoibak, Sarah; Aguirre, Angel Rosas; Toomer, Elizabeth; Rodriguez, Hugo; Llanos Cuentas, Alejandro; D'Alessandro, Umberto; Gamboa, Dionicia; Erhart, Annette

    2013-01-01

    Background While coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset® LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru. Methods The study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses). Results A total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset® LLINs ultimately did not. The LLINs' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], p<0.001). Conclusion Net preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent

  3. A stitch in time: a cross-sectional survey looking at long lasting insecticide-treated bed net ownership, utilization and attrition in SNNPR, Ethiopia

    PubMed Central

    2012-01-01

    Background Since 2002/03, an estimated 4.7 million nets have been distributed in the Southern Nations, Nationalities and Peoples Region (SNNPR) among an at risk population of approximately 10 million people. Evidence from the region suggests that large-scale net ownership rapidly increased over a relatively short period of time. However, little is known about how coverage is being maintained given that the last mass distribution was in 2006/2007. This study sought to determine the status of current net ownership, utilization and rate of long lasting insecticide-treated nets (LLIN) loss in the previous three years in the context of planning for future net distribution to try to achieve sustainable universal coverage. Methods A total of 750 household respondents were interviewed across malarious, rural kebeles of SNNPR. Households were randomly selected following a two-stage cluster sampling design where kebeles were defined as clusters. Kebeles were chosen using proportional population sampling (PPS), and 25 households within 30 kebeles randomly chosen. Results Approximately 67.5% (95%CI: 64.1–70.8) of households currently owned at least one net. An estimated 31.0% (95%CI 27.9–34.4) of all nets owned in the previous three years had been discarded by owners, the majority of whom considered the nets too torn, old or dirty (79.9%: 95%CI 75.8–84.0). Households reported that one-third of nets (33.7%) were less than one year old when they were discarded. The majority (58.8%) of currently owned nets had ‘good’ structural integrity according to a proportionate Hole Index. Nearly two-thirds of households (60.6%) reported using their nets the previous night. The overriding reason for not using nets was that they were too torn (45.7%, 95% CI 39.1–50.7). Yet, few households are making repairs to their nets (3.7%, 95% CI: 2.4–5.1). Conclusions Results suggest that the life span of nets may be shorter than previously thought, with little maintenance by their owners

  4. Evaluation of the efficacy of DDT indoor residual spraying and long-lasting insecticidal nets against insecticide resistant populations of Anopheles arabiensis Patton (Diptera: Culicidae) from Ethiopia using experimental huts

    PubMed Central

    2014-01-01

    Background Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal nets (LLINs) are major malaria vector control tools in Ethiopia. However, recent reports from different parts of the country showed that populations of Anopheles arabiensis, the principal malaria vector, have developed resistance to most families of insecticides recommended for public health use which may compromise the efficacy of both of these key vector control interventions. Thus, this study evaluated the efficacy of DDT IRS and LLINs against resistant populations of An. arabiensis using experimental huts in Asendabo area, southwestern Ethiopia. Methods The susceptibility status of populations of An. arabiensis was assessed using WHO test kits to DDT, deltamethrin, malathion, lambda-cyhalothrin, fenitrothion and bendiocarb. The efficacy of LLIN (PermaNet® 2.0), was evaluated using the WHO cone bioassay. Moreover, the effect of the observed resistance against malaria vector control interventions (DDT IRS and LLINs) were assessed using experimental huts. Results The findings of this study revealed that populations of An. arabiensis were resistant to DDT, deltamethrin, lambda-cyhalothrin and malathion with mortality rates of 1.3%, 18.8%, 36.3% and 72.5%, respectively but susceptible to fenitrothion and bendiocarb with mortality rates of 98.81% and 97.5%, respectively. The bio-efficacy test of LLIN (PermaNet® 2.0) against An. arabiensis revealed that the mosquito population showed moderate knockdown (64%) and mortality (78%). Moreover, mosquito mortalities in DDT sprayed huts and in huts with LLINs were not significantly different (p > 0.05) from their respective controls. Conclusion The evaluation of the efficacy of DDT IRS and LLINs using experimental huts showed that both vector control tools had only low to moderate efficacy against An. arabiensis populations from Ethiopia. Despite DDT being replaced by carbamates for IRS, the low efficacy of LLINs against the resistant population of An

  5. Trends in US President's Malaria Initiative-funded indoor residual spray coverage and insecticide choice in sub-Saharan Africa (2008-2015): urgent need for affordable, long-lasting insecticides.

    PubMed

    Oxborough, Richard M

    2016-01-01

    This article reports the changing pattern of US President's Malaria Initiative-funded IRS in sub-Saharan Africa between 2008 and 2015. IRS coverage in sub-Saharan Africa increased from <2 % of the at-risk population in 2005, to 11 % or 78 million people in 2010, mainly as a result of increased funding from PMI. The scaling up of IRS coverage in sub-Saharan Africa has been successful in several epidemiological settings and contributed to reduced malaria transmission rates. However, the spread and intensification of pyrethroid resistance in malaria vectors led many control programmes to spray alternative insecticides. Between 2009 and 2013, pyrethroid spraying decreased from 87 % (13/15) of PMI-funded countries conducting IRS to 44 % (7/16), while bendiocarb use increased from 7 % (1/15) to 56 % (9/16). Long-lasting pirimiphos-methyl CS received WHOPES recommendation in 2013 and was scheduled to be sprayed in 85 % (11/13) of PMI-funded countries conducting IRS in 2015. The gradual replacement of relatively inexpensive pyrethroids, firstly with bendiocarb (carbamate) and subsequently with pirimiphos methyl CS (organophosphate), has contributed to the downscaling of most PMI-funded IRS programmes. Overall, there was a 53 % decrease in the number of structures sprayed between years of peak coverage and 2015, down from 9.04 million to 4.26 million structures. Sizeable reductions in the number of structures sprayed were reported in Madagascar (56 %, 576,320-254,986), Senegal (64 %, 306,916-111,201), Tanzania (68 %, 1,224,095-389,714) and Zambia (63 %, 1,300,000-482,077), while in Angola, Liberia and Malawi PMI-funded spraying was suspended. The most commonly cited reason was increased cost of pesticides, as vector resistance necessitated switching from pyrethroids to organophosphates. There are worrying preliminary reports of malaria resurgence following IRS withdrawal in parts of Benin, Tanzania and Uganda. The increase in malaria cases following the end of the Global

  6. Impact of long-lasting, insecticidal nets on anaemia and prevalence of Plasmodium falciparum among children under five years in areas with highly resistant malaria vectors

    PubMed Central

    2014-01-01

    Background The widespread use of insecticide-treated nets (LLINs) leads to the development of vector resistance to insecticide. This resistance can reduce the effectiveness of LLIN-based interventions and perhaps reverse progress in reducing malaria morbidity. To prevent such difficulty, it is important to know the real impact of resistance in the effectiveness of mosquito nets. Therefore, an assessment of LLIN efficacy was conducted in malaria prevention among children in high and low resistance areas. Methods The study was conducted in four rural districts and included 32 villages categorized as low or high resistance areas in Plateau Department, south-western Benin. Larvae collection was conducted to measure vector susceptibility to deltamethrin and knockdown resistance (kdr) frequency. In each resistance area, around 500 children were selected to measure the prevalence of malaria infection as well as the prevalence of anaemia associated with the use of LLINs. Results Observed mortalities of Anopheles gambiae s.s population exposed to deltamethrin ranged from 19 to 96%. Knockdown resistance frequency was between 38 and 84%. The prevalence of malaria infection in children under five years was 22.4% (19.9-25.1). This prevalence was 17.3% (14.2-20.9) in areas of high resistance and 27.1% (23.5-31.1) in areas of low resistance (p = 0.04). Eight on ten children that were aged six - 30 months against seven on ten of those aged 31–59 months were anaemic. The anaemia observed in the six to 30-month old children was significantly higher than in the 31–59 month old children (p = 0.00) but no difference associated with resistance areas was observed (p = 0.35). The net use rate was 71%. The risk of having malaria was significantly reduced (p < 0.05) with LLIN use in both low and high resistance areas. The preventive effect of LLINs in high resistance areas was 60% (95% CI: 40–70), and was significantly higher than that observed in low resistance

  7. Long lasting decontamination foam

    DOEpatents

    Demmer, Ricky L.; Peterman, Dean R.; Tripp, Julia L.; Cooper, David C.; Wright, Karen E.

    2010-12-07

    Compositions and methods for decontaminating surfaces are disclosed. More specifically, compositions and methods for decontamination using a composition capable of generating a long lasting foam are disclosed. Compositions may include a surfactant and gelatin and have a pH of less than about 6. Such compositions may further include affinity-shifting chemicals. Methods may include decontaminating a contaminated surface with a composition or a foam that may include a surfactant and gelatin and have a pH of less than about 6.

  8. Status of pyrethroid resistance in Anopheles gambiae s. s. M form prior to the scaling up of Long Lasting Insecticidal Nets (LLINs) in Adzopé, Eastern Côte d’Ivoire

    PubMed Central

    2012-01-01

    Background The growing development of pyrethroid resistance constitutes a serious threat to malaria control programmes and if measures are not taken in time, resistance may compromise control efforts in the foreseeable future. Prior to Long Lasting Insecticidal Nets (LLINs) distribution in Eastern Cote d’Ivoire, we conducted bioassays to inform the National Malaria Control Programme of the resistance status of the main malaria vector, Anopheles gambiae s. s. and the need for close surveillance of resistance. Methods Larvae of An. gambiae s. s. were collected in two areas of Adzopé (Port-Bouët and Tsassodji) and reared to adults. WHO susceptibility tests with impregnated filter papers were carried out to detect resistance to three pyrethroids commonly used to develop LLINs: permethrin 1%, deltamethrin 0.05% and lambda-cyhalothrin 0.05%. Molecular assays were conducted to detect M and S forms and the L1014F kdr allele in individual mosquitoes. Results Resistance, at various degrees was detected in both areas of Adzopé. Overall, populations of An. gambiae at both sites surveyed showed equivalent frequency of the L1014F kdr allele (0.67) but for all tested pyrethroids, there were significantly higher survival rates for mosquitoes from Tsassodji (32–58%) than those from Port-Bouët (3–32%) (p < 0.001), indicating the implication of resistance mechanisms other than kdr alone. During the survey period (May–June) in this forested area of Côte d’Ivoire, An. gambiae s. s. found were exclusively of the M form and were apparently selected for pyrethroid resistance through agricultural and household usage of insecticides. Conclusion Prior to LLINs scaling up in Eastern Côte d’Ivoire, resistance was largely present at various levels in An. gambiae. Underlying mechanisms included the high frequency of the L1014F kdr mutation and other unidentified components, probably metabolic detoxifiers. Their impact on the efficacy of the planned strategy (LLINs) in the

  9. Efficacy of permethrin treated long-lasting insecticidal nets on malaria transmission and observations on the perceived side effects, collateral benefits and human safety in a hyperendemic tribal area of Orissa, India.

    PubMed

    Sharma, Surya K; Tyagi, Prajesh K; Upadhyay, Ashok K; Haque, Mohammed A; Mohanty, Suman S; Raghavendra, Kamaraju; Dash, Aditya P

    2009-11-01

    Studies were conducted on the efficacy of Olyset nets-a long-lasting insecticidal net (LLIN) factory treated with 2% (w/w) permethrin on malaria transmission in an area under the influence of pyrethroid susceptible vector species Anopheles culicifacies and A. fluviatilis in Sundargarh District, Orissa, India. The study area comprised 22 villages that were randomized into three clusters and designated as Olyset net, untreated net, and no net area. Malaria incidence in the study population was measured through longitudinal active surveillance at fortnightly intervals. There was a reduction of 65-70% in malaria incidence in Olyset net area as compared to the control areas. The attack rate of Plasmodium falciparum or number of episodes per person per year in different age groups also showed significant reduction in Olyset net area as compared to untreated net and no net areas. Cross-sectional point prevalence surveys showed 45.7% reduction of malaria prevalence in Olyset net users, whereas there was an increase of 33.3% and 51% in untreated net and no net villages respectively. The compliance rate of Olyset net usage in the study population was 80-98% during different months, whereas it was between 70% and 90% for untreated nets. There were minimal complains of skin irritation (4%), itching (8%) and eye irritation (1.2%). However, these effects were only transitory in nature lasting for few hours of the first usage. Olyset nets also provided collateral benefits in terms of relief not only from mosquitoes and malaria but also from other household pests such as head lice, bed bugs, cockroaches, ants and houseflies. The Olyset nets were found to be safe to humans as no adverse event was recorded in the net users that can be attributed to the use of net. The study showed that Olyset nets are effective personal protection tool that can be used in a community based intervention programme. PMID:19647715

  10. Microdistribution of the resistance of malaria vectors to deltamethrin in the region of Plateau (southeastern Benin) in preparation for an assessment of the impact of resistance on the effectiveness of Long Lasting Insecticidal Nets (LLINs)

    PubMed Central

    2014-01-01

    Background This study aims to research two areas, one with a resistant and the other with a susceptible profile of An. gambiae to deltamethrin in the region of Plateau (southern Benin). In each area, eight localities were sought. Both areas were needed for the assessment of the impact of malaria vector resistance to pyrethroids on the effectiveness of Long Lasting Insecticidal Nets (LLINs). The susceptible area of An. gambiae to deltamethrin was used as a control. Methods In total, 119 localities in the region of Plateau were screened by sampling An. gambiae s.l larvae. Female mosquitoes resulting from these larvae were exposed to 0.05% deltamethrin following WHO standards. PCR was used to identify species and molecular forms of the dead and alive mosquitoes. Finally, we identified kdr mutations (1014 F and1014S) using the HOLA technique. Results Fifty-six out of 119 prospected localities tested positive for Anopheles gambae s.l breeding sites. The results showed that An. gambiae was resistant to deltamethrin in 39 localities and susceptible in only 2 localities; resistance to deltamethrin was suspected in 15 localities. The HOLA technique confirmed the presence of kdr 1014 F mutation and the absence of kdr 1014S mutation. The kdr 1014 F mutation was found in both M and S molecular forms at relatively high frequencies therefore confirming the susceptibility tests. Conclusion We were unable to identify the eight susceptible areas due to the overall resistance of An. gambiae to deltamethrin in the region of Plateau. To implement the study, we kept two areas, one with high resistance (R+++) and the other with low resistance (R+) of An. gambiae to deltamethrin. PMID:24564260

  11. A cross-sectional study assessing the residual bio-efficacy and durability of field-distributed long-lasting insecticidal nets in malaria endemic ethnic communities of Assam, Northeast India.

    PubMed

    Dev, Vas; Barman, Keshab; Khound, Kamal

    2016-01-01

    Long-lasting insecticidal nets (LLINs) are being promoted for malaria vector control in the northeastern Indian state of Assam. A cross-sectional study was conducted to assess the current residual bio-efficacy and durability of both the Olyset(®) and PermaNet(®)2.0 LLINs that were distributed earlier in 2009, 2011 and 2013 to help formulate informed policy regarding net procurement, supplies and replacement. The study was undertaken in three different malaria endemic blocks of Assam during the period of June to October of 2014. The residual bio-efficacies were ascertained using the WHO cone-bioassay method for mosquito mortality post-exposure and corroborated with the ring-net assay for the median knockdown times of both types of LLINs in use by these communities. Cross-sectional community surveys were distributed to assess net ownership, utilization, community practices and the physical conditions of the nets in terms of being torn and the numbers of holes per position. Both the Olyset(®) and PermaNet(®)2.0 LLINs that were distributed in 2009 (i.e., nearly after five years of community usage) were completely torn, worn out and obsolete. However, the LLINs distributed in 2011 (i.e., three years of community usage) retained their residual bio-efficacies in susceptibility ranges that varied from 57% to 79%. However, for the LLINs that were distributed in 2013, the observed residual efficacy was adequate and resulted in a mosquito mortality rate >80 percent. Of the two types of LLINs inspected, the Olyset(®)nets were more durable and robust in terms of being torn less frequently (37.1%, 39/105) compared with the PermaNet(®)2.0 nets (51.8%, 204/394). Regarding the LLINs that were distributed in 2013, all were physically intact and in good condition. The majority of the distributed LLINs (99.2%, 639/644) were still in the possession of the householders of the surveyed populations. This study revealed that the serviceable life of the nets was slightly less than

  12. Polyester based hybrid organic coatings

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojiang

    Polyesters are a class of polymers widely used in organic coatings applications. In this work, four types of organic coatings based on polyester polyols were prepared: UV-curable polyester/poly(meth)acrylate coatings, thermal curable polyester polyurethane-urea coatings, thermal curable non-isocyanate polyurethane coatings, and UV-curable non-isocyanate polyurethane coatings. Polyester/poly(meth)acrylate block copolymers are synthesized using a combination of polycondensation and Atom-Transfer Radical Polymerization (ATRP). All block copolymers are characterized by means of Nuclear Magnetic Resonance (NMR) and Gel Permeation Chromatography (GPC). In the case of unsaturated-polyester-based block copolymers the main chain double bond in the polyester backbone remains almost unaffected during ATRP. The unsaturated block copolymers are crosslinkable and can form networks upon photo-irradiation in the presence of a suitable photoinitiator. These copolymers might be interesting candidates for coatings with better overall properties than those based on neat polyesters. Thermal curable polyester polyol based Polyurethane-Urea (PUU) coatings were formulated using Partially Blocked HDI isocyanurate (PBH), Isophorone Diamine (IPDA), and polyester polyol. As a comparison, the polyurethane coatings (PU) without adding IPDA were also prepared. The mechanical and viscoelastic properties of the PUU and PU coating were investigated by using tensile test and Dynamic Mechanical Thermal Analyzer (DMTA). It was found that PUU coating exhibited higher crosslink density, Tg, tensile modulus and strength than the corresponding PU coating. Thermal curable non-isocyanate polyurethane coatings were prepared by using polyamine and cyclic carbonate terminated polyester. Cyclic carbonate terminated polyester was synthesized from the reaction of the carbon dioxide and epoxidized polyester which was prepared from the polyester polyol. The properties of the epoxidized and cyclic carbonate

  13. Colorful Demos with a Long-Lasting Soap Bubble.

    ERIC Educational Resources Information Center

    Behroozi, F.; Olson, D. W.

    1994-01-01

    Describes several demonstrations that feature interaction of light with soap bubbles. Includes directions about how to produce a long-lasting stationary soap bubble with an easily changeable size and describes the interaction of white light with the bubble. (DDR)

  14. Intact and long-lasting repetition priming in amnesia.

    PubMed

    Cave, C B; Squire, L R

    1992-05-01

    In 2 experiments, we evaluated the ability of amnesic patients to exhibit long-lasting perceptual priming after a single exposure to pictures. Ss named pictures as quickly as possible on a single occasion, and later named the same pictures mixed with new pictures. In Experiment 1, amnesic patients exhibited fully intact priming effects lasting at least 7 days. In Experiment 2, the priming effect for both groups was shown to depend on both highly specific visual information and on less visual, more conceptual information. In contrast, recognition memory was severely impaired in the patients, as assessed by both accuracy and response time. The results provide the first report of a long-lasting priming effect in amnesic patients, based on a single encounter, which occurs as strongly in the patients as in normal Ss. Together with other recent findings, the results suggest that long-lasting priming and recognition memory depend on separate brain systems. PMID:1534352

  15. Control of Culicoides sonorensis (Diptera: Ceratopogonidae) blood feeding on sheep with long-lasting repellent pesticides.

    PubMed

    Reeves, W K; Lloyd, J E; Stobart, R; Stith, C; Miller, M M; Bennett, K E; Johnson, G

    2010-09-01

    Culicoides sonorensis is the primary vector of bluetongue and epizootic hemorrhagic disease viruses in North America. Bluetongue disease is one of the most economically important arthropod-borne diseases of sheep in North America, because it causes significant morbidity and mortality and can lead to local quarantines and international trade restrictions. Long-lasting repellent pesticides could be applied to sheep as they are moved down from mountain pastures to protect them from biting midges until the 1st frost. We tested long-lasting pesticides on sheep as repellents against C. sonorensis. Both Python ear tags with 10% zeta-cypermethrin (9.8 g/tag) synergized with 20% piperonyl butoxide (PBO) and a 12-ml low-volume spray application of ready-to-use sheep insecticide (Y-TEX) with 2.5% permethrin and 2.5% PBO in an oil-based formulation were repellent to C. sonorensis for at least 3-5 wk after a single application. PMID:21033057

  16. Adolescent ethanol exposure: does it produce long lasting electrophysiological effects?

    PubMed Central

    Ehlers, Cindy L.; Criado, José R.

    2009-01-01

    This review discusses evidence for long lasting neurophysiological changes that may occur following exposure to ethanol during adolescent development in animal models. Adolescence is the time that most individuals first experience ethanol exposure and binge drinking is not uncommon during adolescence. If alcohol exposure is neurotoxic to the developing brain during adolescence, not unlike it is during fetal development, then understanding how ethanol affects the developing adolescent brain becomes a major public health issue. Adolescence is a critical time period when cognitive, emotional and social maturation occurs and it is likely that ethanol exposure may affect these complex processes. In order to study the effects of ethanol on adolescent brain animal models where the dose and time of exposure can be carefully controlled that closely mimic the human condition are needed. The studies reviewed provide evidence that demonstrates that relatively brief exposure to high levels of ethanol, via ethanol vapours, during a period corresponding to parts of adolescence in the rat is sufficient to cause long-lasting changes in functional brain activity. Disturbances in waking EEG and a reduction in the P3 component of the ERP have been demonstrated in adult rats that were exposed to ethanol vapour during adolescence. Adolescent ethanol exposure was also found to produce long lasting reductions in the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS, a finding consistent with a premature aging of sleep. Further studies are necessary to confirm these findings, in a range of strains, and to link those findings to the neuroanatomical and neurochemical mechanisms potentially underlying the lasting effects of adolescent ethanol exposure. PMID:20113872

  17. Multiple Pathways to Long-lasting Phrenic Motor Facilitation

    PubMed Central

    Dale-Nagle, Erica A.; Hoffman, Michael S.; MacFarlane, Peter M.; Mitchell, Gordon S.

    2010-01-01

    Plasticity is a hallmark of neural systems, including the neural system controlling breathing (Mitchell and Johnson, 2003). Despite its biological and potential clinical significance, our understanding of mechanisms giving rise to any form of respiratory plasticity remains incomplete. Here we discuss recent advances in our understanding of cellular mechanisms giving rise to phrenic long-term facilitation (pLTF), a long-lasting increase in phrenic motor output induced by acute intermittent hypoxia (AIH). Recently, we have come to realize that multiple, distinct mechanisms are capable of giving rise to long-lasting phrenic motor facilitation (PMF); we use PMF as a general term that includes AIH-induced pLTF. It is important to begin an appreciation and understanding of these diverse pathways. Hence, we introduce a nomenclature based on upstream steps in the signaling cascade leading to PMF. Two pathways are featured here: the “Q” and the “S” pathways, named because they are induced by metabotropic receptors coupled to Gq and Gs proteins, respectively. These pathways appear to interact in complex and interesting ways, thus providing a range of potential responses in the face of changing physiological conditions or the onset of disease. PMID:20217354

  18. Characterizing Interplanetary Structures of Long-Lasting Ionospheric Storm Events

    NASA Astrophysics Data System (ADS)

    Tandoi, C.; Dong, Y.; Ngwira, C. M.; Damas, M. C.

    2015-12-01

    Geomagnetic storms can result in periods of heightened TEC (Total Electron Content) in Earth's ionosphere. These periods of change in TEC (dTEC) can have adverse impacts on a technological society, such as scintillation of radio signals used by communication and navigation satellites. However, it is unknown which exact properties of a given storm cause dTEC. We are comparing different solar wind properties that result in a significant long-lasting dTEC to see if there are any patterns that remain constant in these storms. These properties, among others, include the interplanetary magnetic field By and Bz components, the proton density, and the flow speed. As a preliminary investigation, we have studied 15 solar storms. Preliminary results will be presented. In the future, we hope to increase our sample size and analyze over 80 different solar storms, which result in significant dTEC.

  19. Distributional learning has immediate and long-lasting effects.

    PubMed

    Escudero, Paola; Williams, Daniel

    2014-11-01

    Evidence of distributional learning, a statistical learning mechanism centered on relative frequency of exposure to different tokens, has mainly come from short-term learning and therefore does not ostensibly address the development of important learning processes. The present longitudinal study examines both short- and long-term effects of distributional learning of phonetic categories on non-native sound discrimination over a 12-month period. Two groups of listeners were exposed to a two-minute distribution of auditory stimuli in which the most frequently presented tokens either approximated or exaggerated the natural production of the speech sounds, whereas a control group listened to a piece of classical music for the same length of time. Discrimination by listeners in the two distribution groups improved immediately after the short exposure, replicating previous results. Crucially, this improvement was maintained after six and 12 months, demonstrating that distributional learning has long-lasting effects. PMID:25128798

  20. Long-lasting antifog plasma modification of transparent plastics.

    PubMed

    Di Mundo, Rosa; d'Agostino, Riccardo; Palumbo, Fabio

    2014-10-01

    Antifog surfaces are necessary for any application requiring optical efficiency of transparent materials. Surface modification methods aimed toward increasing solid surface energy, even when supposed to be permanent, in fact result in a nondurable effect due to the instability in air of highly hydrophilic surfaces. We propose the strategy of combining a hydrophilic chemistry with a nanotextured topography, to tailor a long-lasting antifog modification on commercial transparent plastics. In particular, we investigated a two-step process consisting of self-masked plasma etching followed by plasma deposition of a silicon-based film. We show that the deposition of the silicon-based coatings on the flat (pristine) substrates allows a continuous variation of wettability from hydrophobic to superhydrophilic, due to a continuous reduction of carbon-containing groups, as assessed by Fourier transform infrared and X-ray photoelectron spectroscopies. By depositing these different coatings on previously nanotextured substrates, the surface wettability behavior is changed consistently, as well as the condensation phenomenon in terms of microdroplets/liquid film appearance. This variation is correlated with advancing and receding water contact angle features of the surfaces. More importantly, in the case of the superhydrophilic coating, though its surface energy decreases with time, when a nanotextured surface underlies it, the wetting behavior is maintained durably superhydrophilic, thus durably antifog. PMID:25251610

  1. Rapid and long-lasting learning of feature binding.

    PubMed

    Yashar, Amit; Carrasco, Marisa

    2016-09-01

    How are features integrated (bound) into objects and how can this process be facilitated? Here we investigated the role of rapid perceptual learning in feature binding and its long-lasting effects. By isolating thecontributions of individual features from their conjunctionsbetween training and test displays, we demonstrate for the first time that training can rapidly and substantially improve feature binding. Observers trained on a conjunction search task consisting of a rapid display with one target-conjunction, then tested with a new target-conjunction. Features were the same between training and test displays. Learning transferred to the new target when its conjunction was presented as a distractor, but not when only its component features were presented in different conjunction distractors during training. Training improvement lasted for up to 16months, but, in all conditions, it was specific to the trained target. Our findings suggest that with short training observers' ability to bind two specific features into an object is improved, and that this learning effect can last for over a year. Moreover, our findings show that while the short-term learning effect reflects activation of presented items and their binding, long-term consolidation is task specific. PMID:27289484

  2. Immunogenicity of long-lasting recombinant factor VIII products.

    PubMed

    Ing, Mathieu; Gupta, Nimesh; Teyssandier, Maud; Maillère, Bernard; Pallardy, Marc; Delignat, Sandrine; Lacroix-Desmazes, Sébastien

    2016-03-01

    Replacement therapy for patients with hemophilia A using plasma-derived or recombinant factor VIII (FVIII) is complicated by the short half-life of the FVIII products and by the occurrence of neutralizing antibodies in a substantial number of patients. In the recent years, enormous efforts have been invested to develop new generations of coagulation factors with extended half-lives. Presumably, the use of long-lasting FVIII products should reduce the frequency of administration to the patients and drastically improve their quality of life. The question of their immunogenicity remains however unanswered as yet. The present review proposes a summary of the different strategies developed to enhance the half-life of FVIII, including fusion of FVIII to the Fc fragment of the human IgG1 or to human serum albumin, or attachment of polyethylene glycol. Based on the available literature, we hypothesize on the potential benefits or risks associated with each of the latter strategies in terms of immunogenicity of the newly derived hemostatic drugs. PMID:26723503

  3. Red long-lasting phosphorescence based on color conversion process

    NASA Astrophysics Data System (ADS)

    Li, Zhanjun; Zhang, Hongwu; Fu, Haixia

    2013-01-01

    The principle of color conversion process was used to generate red long-lasting phosphorescence (LLP) using SrAl2O4:Eu, Dy (SAO) as primary light source and rhodamine B encapsulated mesoporous silica nanoparticles (MCM-R) as effective color conversion agent. The phosphorescence spectra of MCM-R/SAO hybrid samples show green peaks from 425 nm to 550 nm and red peaks from 550 nm to 700 nm, which can be attributed to the phosphorescence of SAO and the fluorescence of MCM-R, respectively. The phosphorescence color can be adjusted from green to red by changing the mass ratio of MCM-R/SAO. When the mass ratio of MCM-R/SAO increases from 0.05 to 1.5, a blue shift for the green peak and a red shift for the red peak of the phosphorescence spectra can be observed and the intensity of the red emission peak increase relatively towards the green one. The phosphorescence decay curves show that MCM-R and SAO have similar decay dynamics and the MCM-R can inherit the LLP properties of SAO. The phosphorescence decay spectra indicate that the MCM-R/SAO hybrid can retain constant and steady visual phosphorescence color. The red phosphorescence can be seen in the dark with naked eyes for more than 5 h. So, the red LLP can be successfully achieved based on the principle of color conversion process.

  4. Long-lasting bradypnea induced by repeated social defeat.

    PubMed

    Brouillard, Charly; Carrive, Pascal; Camus, Françoise; Bénoliel, Jean-Jacques; Similowski, Thomas; Sévoz-Couche, Caroline

    2016-08-01

    Repeated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days. Respiratory rate was recorded under anesthesia 6 days (D+10) or 26 days (D+30) after social defeat. At D+10, defeated (D) rats spent less time in the open arms of the elevated plus maze test, had heavier adrenal glands, and displayed bradypnea, unlike nondefeated animals. At D+30, all signs of anxiety had disappeared. However, one-half of the rats still displayed bradypnea (DL rats, for low respiratory rate indicated by a lower RSA frequency), whereas those with higher respiratory rate (DH rats) had recovered. Acute blockade of the dorsomedial hypothalamus (DMH) or nucleus tractus solitarii (NTS) 5-HT3 receptors reversed bradypnea in all D rats at D+10 and in DL rats at D+30. Respiratory rate was also recorded in conscious animals implanted with radiotelemetric ECG probes. DH rats recovered between D+10 and D+18, whereas DL rats remained bradypneic until D+30. In conclusion, social stress induces sustained chronic bradypnea mediated by DMH neurons and NTS 5-HT3 receptors. These changes are associated with an anxiety-like state that persists until D+10, followed by recovery. However, bradypnea may persist in one-half of the population up until D+30, despite apparent recovery of the anxiety-like state. PMID:27225946

  5. Long-lasting virtual motorcycle-riding trainer effectiveness

    PubMed Central

    Vidotto, Giulio; Tagliabue, Mariaelena; Tira, Michael D.

    2015-01-01

    This work aimed to test the long-lasting effects of learning acquired with a virtual motorcycle-riding trainer as a tool to improve hazard perception. During the simulation, the rider can interact with other road actors and experience the most common potential accident situations in order to learn to modify his or her behavior to anticipate hazards and avoid crashes. We compared performance to the riding simulator of the two groups of participants: the experimental group, which was trained with the same simulator one year prior, and the control group that had not received any type of training with a riding or driving simulator. All of the participants had ridden a moped in the previous 12 months. The experimental group showed greater abilities to avoid accidents and recognize hazards in comparison to their performance observed a year before, whereas the performance of the control group was similar to that of the experimental group 1 year before in the first two sessions, and even better in the third. We interpreted this latter result as a consequence of their prior on-road experience. Also, the fact that the performance of the experimental group at the beginning of the follow-up is better than that recorded at the end of the training—1 year before—is in line with the idea of a transfer from the on-road experience to the simulator. The present data confirm our main expectation that the effectiveness of the riding training simulator on the ability to cope with potentially dangerous situations persists over time and provides additional evidence in favor of the idea that simulators may be considered useful tools for training the ability to detect and react to hazards, leading to an improvement of this higher-order cognitive skill that persists over time. Implications for the reciprocal influence of the training with the simulator and the on-the road experience are discussed as well. PMID:26579036

  6. Field Topology Analysis of a Long-lasting Coronal Sigmoid

    NASA Astrophysics Data System (ADS)

    Savcheva, A. S.; van Ballegooijen, A. A.; DeLuca, E. E.

    2012-01-01

    We present the first field topology analysis based on nonlinear force-free field (NLFFF) models of a long-lasting coronal sigmoid observed in 2007 February with the X-Ray Telescope on Hinode. The NLFFF models are built with the flux rope insertion method and give the three-dimensional coronal magnetic field as constrained by observed coronal loop structures and photospheric magnetograms. Based on these models, we have computed horizontal maps of the current and the squashing factor Q for 25 different heights in the corona for all six days of the evolution of the region. We use the squashing factor to quantify the degree of change of the field line linkage and to identify prominent quasi-separatrix layers (QSLs). We discuss the major properties of these QSL maps and devise a way to pick out important QSLs since our calculation cannot reach high values of Q. The complexity in the QSL maps reflects the high degree of fragmentation of the photospheric field. We find main QSLs and current concentrations that outline the flux rope cavity and that become characteristically S-shaped during the evolution of the sigmoid. We note that, although intermittent bald patches exist along the length of the sigmoid during its whole evolution, the flux rope remains stable for several days. However, shortly after the topology of the field exhibits hyperbolic flux tubes (HFT) on February 7 and February 12 the sigmoid loses equilibrium and produces two B-class flares and associated coronal mass ejections (CMEs). The location of the most elevated part of the HFT in our model coincides with the inferred locations of the two flares. Therefore, we suggest that the presence of an HFT in a coronal magnetic configuration may be an indication that the system is ready to erupt. We offer a scenario in which magnetic reconnection at the HFT drives the system toward the marginally stable state. Once this state is reached, loss of equilibrium occurs via the torus instability, producing a CME.

  7. Eye Study Underscores the Long-Lasting Benefits of Controlling Diabetes

    MedlinePlus

    ... Monday, June 13, 2016 Eye study underscores the long-lasting benefits of controlling diabetes NIH-funded study ... received intensive glycemic therapy in the 10-year-long Diabetes Control and Complications Trial on average had ...

  8. Long-lasting desynchronization in rat hippocampal slice induced by coordinated reset stimulation

    SciTech Connect

    Tass, P. A.; Barnikol, U. B.; Silchenko, A. N.; Hauptmann, C.; Speckmann, E.-J.

    2009-07-15

    In computational models it has been shown that appropriate stimulation protocols may reshape the connectivity pattern of neural or oscillator networks with synaptic plasticity in a way that the network learns or unlearns strong synchronization. The underlying mechanism is that a network is shifted from one attractor to another, so that long-lasting stimulation effects are caused which persist after the cessation of stimulation. Here we study long-lasting effects of multisite electrical stimulation in a rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that desynchronizing coordinated reset stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with a widespread decrease in the amplitude of the epileptiform activity. In contrast, periodic stimulation induces a long-lasting increase in both synchronization and amplitude.

  9. Long-Lasting Sparks: Multi-Metastability and Release Competition in the Calcium Release Unit Network

    PubMed Central

    Song, Zhen; Karma, Alain; Weiss, James N.; Qu, Zhilin

    2016-01-01

    Calcium (Ca) sparks are elementary events of biological Ca signaling. A normal Ca spark has a brief duration in the range of 10 to 100 ms, but long-lasting sparks with durations of several hundred milliseconds to seconds are also widely observed. Experiments have shown that the transition from normal to long-lasting sparks can occur when ryanodine receptor (RyR) open probability is either increased or decreased. Here, we demonstrate theoretically and computationally that long-lasting sparks emerge as a collective dynamical behavior of the network of diffusively coupled Ca release units (CRUs). We show that normal sparks occur when the CRU network is monostable and excitable, while long-lasting sparks occur when the network dynamics possesses multiple metastable attractors, each attractor corresponding to a different spatial firing pattern of sparks. We further highlight the mechanisms and conditions that produce long-lasting sparks, demonstrating the existence of an optimal range of RyR open probability favoring long-lasting sparks. We find that when CRU firings are sparse and sarcoplasmic reticulum (SR) Ca load is high, increasing RyR open probability promotes long-lasting sparks by potentiating Ca-induced Ca release (CICR). In contrast, when CICR is already strong enough to produce frequent firings, decreasing RyR open probability counter-intuitively promotes long-lasting sparks by decreasing spark frequency. The decrease in spark frequency promotes intra-SR Ca diffusion from neighboring non-firing CRUs to the firing CRUs, which helps to maintain the local SR Ca concentration of the firing CRUs above a critical level to sustain firing. In this setting, decreasing RyR open probability further suppresses long-lasting sparks by weakening CICR. Since a long-lasting spark terminates via the Kramers’ escape process over a potential barrier, its duration exhibits an exponential distribution determined by the barrier height and noise strength, which is modulated

  10. Assessment of Long-Lasting Insecticidal Nets (LLINs) on Vectors and Malaria Transmission in the Commune of Aguegues, Benin

    PubMed Central

    Modeste Gouissi, Fadéby; Salifou, Sahidou; Patrick Edorh, Aléodjrodo; Anges Yadouleton, William; Djenontin, Armel; Bio-Banganna, Sahabi; Geoffroy Augustin Gouissi, Sègbèhin; Akogbeto, Martin

    2012-01-01

    Introduction To overcome the problems of periodic re-impregnation of mosquito nets and low rates of treatment, the commune of Aguegues was chosen to evaluate the effects of Olyset® nets on malaria transmission and against An. gambiae. Methods 87 old Olyset® nets installed five years ago were identified in the village ‘Akpadon’. 10 untreated nets were installed in 10 structures of type “a bedroom and parlour” in the village ‘Akodji’. Four rooms without nets were identified in the village ‘Donoukpa’. Entomological and epidemiological evaluations were conducted during the May to October 2011. 24 sessions of capture or 2088 men-nights resulted in the capture of 30,608 mosquitoes. Results The entrance of anopheles was significantly reduced in the village with Olyset® nets. 45% of mosquitoes captured inside rooms with Olyset® nets were found dead after 24 hrs of obser-vation. Overall, parasitemia was very low in the treated village (4.52%). 18 (4.64%) cases of malaria fever were from Akpadon with 7.5% positive blade smear, 29 (10.98%) were from Akodji with 8.37% positive blade smear, and 80 (95.23%) come from Donoukpa with 38.09% positive blade smear. The Olyset® nets and untreated net were adjusted hemoglobin levels. Conclusion Olyset® net had a very high knock down effect and is an alternative in malaria control. PMID:23678454

  11. Does foreplay matter? Gammarus pulex females may benefit from long-lasting precopulatory mate guarding

    PubMed Central

    Galipaud, Matthias; Dechaume-Moncharmont, François-Xavier; Oughadou, Abderrahim; Bollache, Loïc

    2011-01-01

    Precopulatory mate guarding (PCMG) is generally assumed to be costly for both sexes. However, males may gain by displaying long-lasting mate guarding under strong male–male competition. Surprisingly, the potential for females to benefit from being held by males has been largely overlooked in previous studies. In Gammarus pulex, an amphipod crustacean, PCMG lasts several weeks, yet females are described as bearing only cost from such male mating strategy. We investigated potential female benefits by assessing the effect of mate guarding on her intermoult duration. Unpaired females had longer intermoult duration than paired females. Intermoult duration clearly decreased when paired females engaged in early and long-lasting mate guarding. In addition, short intermoults and long-lasting mate guarding had no effect on egg number. These results highlight a potential benefit associated with PCMG for G. pulex females, suggesting that the strength of an intersexual conflict over its duration may be overestimated. PMID:21068026

  12. Long Lasting Protein Synthesis- and Activity-Dependent Spine Shrinkage and Elimination after Synaptic Depression

    PubMed Central

    Ramiro-Cortés, Yazmín; Israely, Inbal

    2013-01-01

    Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation. PMID:23951097

  13. A short bout of HFD promotes long-lasting hepatic lipid accumulation

    PubMed Central

    Chiazza, Fausto; Challa, Tenagne D; Lucchini, Fabrizio C; Konrad, Daniel; Wueest, Stephan

    2016-01-01

    abstract A short bout of high fat diet (HFD) impairs glucose tolerance and induces hepatic steatosis in mice. Here, we aimed to elaborate on long-lasting effects of short-term high fat feeding. As expected, one week of HFD significantly impaired glucose tolerance. Intriguingly, recovery feeding with a standard rodent diet for 8 weeks did not fully normalize glucose tolerance. In addition, mice exposed to a short bout of HFD revealed significantly increased liver fat accumulation paralleled by elevated portal free fatty acid levels after 8 weeks of recovery feeding compared to exclusively chow-fed littermates. In conclusion, a short bout of HFD has long-lasting effects on hepatic lipid accumulation and glucose tolerance. PMID:27144100

  14. Branch-PCR Constructed Stable shRNA Transcription Nanoparticles Have Long-Lasting RNAi Effect.

    PubMed

    Liu, Jianbing; Wang, Runyu; Ma, Dejun; Li, Yanyan; Wei, Chao; Xi, Zhen

    2016-06-01

    RNA interference (RNAi) is a cellular process for gene silencing. Because of poor serum stability, transferring dsRNA directly into the target cells is a challenge. We report a facile and universal strategy to construct short hairpin RNA (shRNA) transcription nanoparticles with multiple shRNA transcription templates by PCR with flexible branched primers (branch-PCR). Compared with conventional linear shRNA transcription templates, these shRNA transcription nanoparticles show excellent stability against digestion by exonuclease III. Importantly, we found that our highly stable shRNA transcription nanoparticles can also be transcribed and thus induce efficient and long-lasting RNAi with picomolar activity in living mammalian cells. These chemically well-defined branch-PCR-generated stable shRNA transcription nanoparticles might facilitate RNAi delivery with a long-lasting RNAi effects. PMID:26972444

  15. Monitoring the hydrolytic degradation of polyester-based composites by a piezoelectric method

    SciTech Connect

    Sainte-Pierre, N.; Perrissin, I.; Jayet, Y.; Tatiboueet, J.

    1995-10-01

    Theoretical considerations show that the electric impedance of a piezoelectric element depends on the physical and geometrical properties of the element and also on the viscoelastic characteristics of the different media surrounding it. According to a dynamic model, an original technique has been developed by inserting a piezoelectric ceramic in the composite structure when processed. The electric signal, after signal processing and numerical treatments, gives access to the viscoelastic properties of the external medium. This method is an excellent indicator to display the polymerization kinetics of the resin as well as the post-curing phase of the composite structure process. Moreover, a further application of this non-destructive method is the monitoring of the hydrolitic degradation of the composite structure. The evolution of the electric impedance of the piezoelectric sensor is presented here as a function of water exposition time for a polyester-based composite.

  16. Preventing long-lasting fear recovery using bilateral alternating sensory stimulation: A translational study.

    PubMed

    Wurtz, H; El-Khoury-Malhame, M; Wilhelm, F H; Michael, T; Beetz, E M; Roques, J; Reynaud, E; Courtin, J; Khalfa, S; Herry, C

    2016-05-01

    Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery. PMID:26091614

  17. Visual reactions in a case of long-lasting cortical blindness

    PubMed Central

    Braak, J. W. G. Ter; Schenk, V. W. D.; Vliet, A. G. M. Van

    1971-01-01

    A case is described of long-lasting cortical blindness in a 71 year old man showing no other visual reactions than pupillary narrowing to light and (only after some months) optokinetic nystagmus of the `passive' type. Necropsy demonstrated total bilateral destruction of the striate area of the cortex caused by bilateral softening in the territory of the posterior cerebral artery, and nearly total loss of ganglion cells in both lateral geniculate bodies. Images

  18. Long-lasting airplane headache in a patient with chronic rhinosinusitis.

    PubMed

    Pfund, Z; Trauninger, A; Szanyi, I; Illes, Z

    2010-04-01

    The authors report long-lasting airplane headache in a patient with non-allergic, chronic rhinosinusitis. Association of mucosal inflammation with compromised sinonasal ventilation and sinus barotrauma created a base for not only the pain but also for the prolongation of symptoms. Effective therapy with antihistamine and nasal decongestant supports the theory that sinonasal barotrauma plays a triggering role in the pathophysiology of airplane headache. PMID:19515126

  19. Long-lasting control of Anopheles arabiensis by a single spray application of micro-encapsulated pirimiphos-methyl (Actellic® 300 CS)

    PubMed Central

    2014-01-01

    performance of p-methyl CS was consistent in bioassays and experimental huts. The CS outperformed the EC in laboratory and hut bioassays but the EC longevity in huts was unexpected. Long-lasting p-methyl CS formulations should be more effective than both p-methyl EC and bendiocarb considering a single spray could be sufficient for annual malaria control. IRS with p-methyl 300 CS is a timely addition to the limited portfolio of long-lasting residual insecticides. PMID:24476070

  20. Long-lasting upper D-region ionospheric modifications caused by intense +/- CG lightning discharges

    NASA Astrophysics Data System (ADS)

    Haldoupis, Christos

    2013-04-01

    In a recent Geophysical Research Letter we have presented observations from a single maritime storm showing that intense positive cloud-to-ground (+CG) lightning discharges during nighttime, which trigger both an elve and a sprite, are associated with long-lasting conductivity modifications in the upper D-region ionosphere. The ionospheric disturbances can be observed as perturbations in the amplitude and phase of VLF (very low frequency) signals propagating through or near the disturbed region. They are manifested as LOng Recovery early VLF Events (LOREs) which can last up to 20 - 30 minutes. The same ionospheric modifications may also produce abrupt step-like changes in VLF transmissions which offset signal levels for longer times (>30-60 min). Here we discuss these observations supplementing them with new evidence and some statistics. Among other things, the unpublished results show that very intense (currents > 250-300 kA) CG lightning discharges of either positive or negative polarity are always accompanied mainly by step-like LOREs. The evidence suggests that the electromagnetic pulse (EMP) of a very high peak current CG lightning stroke, which is likely able to produce an elve, produces by electron impact long lasting and spatially extended elevations in electron density at VLF ionospheric reflection heights in the upper D region ionosphere. The results identify a mechanism for the LORE VLF signatures and confirm predictions and postulations that elves may be accompanied by significant and long-lasting electron density perturbations in the upper D- lower E- region ionosphere.

  1. Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain

    PubMed Central

    Ono, Munenori; Bishop, Deborah C.; Oliver, Douglas L.

    2016-01-01

    Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound. PMID:26867811

  2. [Efficacy, toxicity and mechanism of insecticide KR-100: a preliminary study].

    PubMed

    Zhi, Guo-Zhou; Chen, Xiao-Guang; Zheng, Xue-Li; Chai, Ke-Sheng; Chen, Jin-Bo; Lin, Li-Feng; Cai, Song-Wu

    2002-04-01

    KR-100 is a newly developed long-lasting insecticide that incorporates cinerins substance, drug-release control substance and synergistic agent following certain procedures under carefully regulated conditions. Tests of the efficacy, toxicity, stability and long-term effect of KR-100 were conducted, and it was show that the insecticide possessed strong and long-lasting effect against mosquitoes, flies and cockroaches but was by no means toxic to human. Morphological study of KR-100 under scanning electron microscope revealed porous membrane form. This insecticide, therefore, can be safely applied with good pesticidal effect. PMID:12390738

  3. A sustained rat model for studying the long-lasting catabolic state of sepsis.

    PubMed

    Breuille, D; Voisin, L; Contrepois, M; Arnal, M; Rose, F; Obled, C

    1999-03-01

    Most animal models of sepsis induced high mortality or early recovery and do not mimic the long-lasting catabolic state observed in patients. The purpose of this study is to develop a model of sepsis which reproduces these disorders, especially the long-lasting muscle wasting. This report summarizes our observations in a series of seven experiments using this model with rats to study the route of live Escherichia coli administration, dose of bacteria, reproducibility of the model, bacterial count in tissues, comparison of injection of live or dead bacteria, metabolic perturbations linked to infection, and potential role of tumor necrosis factor alpha (TNF-alpha) in muscle wasting. After intravenous infection, animals were anorexic and the catabolic state was long-lasting: body weight loss for 2 to 3 days followed by a chronic wasting state for several days. Liver, spleen, lung protein content, and plasma concentration of alpha2-macroglobulin were increased 2 and 6 days after infection. At 6 days, muscle protein content was substantially (-40%) reduced. The plasma TNF-alpha level measured 1.5 h after infection correlated with body weight loss observed 9 days later. The inhibition of TNF-alpha secretion by administration of pentoxifylline 1 h before infection reduced muscle wasting and activation of proteolysis at day 2 and abolished them at day 6. This septic model mimics in rats the prolonged protein metabolism alterations and muscle atrophy characteristics of infected patients and thus is useful for studying the impact of nutritional support on outcome. PMID:10024546

  4. The substrate for long-lasting memory: if not protein synthesis, then what?

    PubMed Central

    Routtenberg, Aryeh

    2011-01-01

    The prevailing textbook view that de novo protein synthesis is required for memory (e.g., Bear, 2006) is seriously flawed and the alternative hypothesis has been proposed in which post-translational modification (PTM) of proteins already synthesized and already present within the synapse is ‘the’ substrate for long-lasting memory (Routtenberg and Rekart, 2005). Protein synthesis serves a replenishment role. The first part of this review discusses how long-lasting memory can be achieved with ‘only’ PTM of existing synaptic proteins. The second part critically reviews a recent report published in Neuron 2007 that exemplifies the current view of protein synthesis and memory while also illustrating how these results can be understood within this new PTM framework. A necessary yet unexpected conclusion to emerge from consideration of the consequences of a PTM mechanism as the necessary, sufficient and exclusive substrate for long-lasting memory (Routtenberg and Rekart, 2005), is that the central Hebbian dogma that cells that ‘fire together, wire together’ is an unlikely mechanism for long-lasting memory. Thus, a unique feature of the PTM model is that longevity of information storage is achieved not by stability of the synaptic mechanism, but by impermanent pseudoredundant circuits. This is so because PTM is a reversible process and thus any permanent connection, any ‘lasting effect’ cannot be in the form of stable synapse formation. We have therefore proposed a solution in which network level processes regulate cellular mechanisms, even as such mechanisms regulate the network. Thus, synapses are ‘meta-stabilized’ by regulated feedback mediated by the circuit in which the synapse is embedded. For example, spontaneous activity is proposed to be a substrate feedback mechanism we term ‘cryptic rehearsal’ to sustain for some period of time after learning an approximation to the state initially created by input. Additionally, because the duplication

  5. The substrate for long-lasting memory: if not protein synthesis, then what?

    PubMed

    Routtenberg, Aryeh

    2008-03-01

    The prevailing textbook view that de novo protein synthesis is required for memory (e.g., [Bear, M. F., Connors, B., & Paradiso, M. 2006. Neuroscience. Lippincott, New York]) is seriously flawed and an alternative hypothesis has been proposed in which post-translational modification (PTM) of proteins already synthesized and already present within the synapse is 'the' substrate for long-lasting memory. Protein synthesis serves a replenishment role. The first part of this review discusses how long-lasting memory can be achieved with 'only' PTM of existing synaptic proteins. The second part critically reviews a recent report published in Neuron 2007 that exemplifies the current view of protein synthesis and memory while also illustrating how these results can be understood within this new PTM framework. A necessary yet unexpected conclusion to emerge from consideration of the consequences of a PTM mechanism as the necessary, sufficient and exclusive substrate for long-lasting memory, is that the central Hebbian dogma that cells that 'fire together, wire together' is an unlikely mechanism for long-lasting memory. Thus, a unique feature of the PTM model is that longevity of information storage is achieved not by stability of the synaptic mechanism, but by impermanent pseudoredundant circuits. This is so because PTM is a reversible process and thus any permanent connection, any 'lasting effect' cannot be in the form of stable synapse formation. We have therefore proposed a solution in which network level processes regulate cellular mechanisms, even as such mechanisms regulate the network. Thus, synapses are 'meta-stabilized' by regulated feedback mediated by the circuit in which the synapse is embedded. For example, spontaneous activity is proposed to be a substrate feedback mechanism we term 'cryptic rehearsal' to sustain for some period of time after learning an approximation to the state initially created by input. Additionally, because the duplication of these traces

  6. PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine

    PubMed Central

    Xue, Wenda; Wang, Wei; Gong, Tong; Zhang, Hailou; Tao, Weiwei; Xue, Lihong; Sun, Yan; Wang, Fushun; Chen, Gang

    2016-01-01

    Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju. One day post Yueju in Kunming but not ICR strain mice, expression of total and phosphorylated CREB, as well as the CREB signaling activator, PKA (protein kinase A) was up-regulated in the hippocampus. Although BDNF gene expression increased at 3 hours in both strains, it remained up-regulated at 1 day only in Kunming mice. Ketamine showed similar strain-dependent behavioral effects. However, blockade of PKA/CREB signaling blunted the antidepressant effects and reversed the up-regulation of BDNF gene expression by Yueju, but not ketamine. Conversely, blockade of mammalian target of rapamycin signaling led to opposite effects. Taken altogether, prolonged transcriptional up-regulation of hippocampal BDNF may account for the stain-dependent enduring antidepressant responses to Yueju and ketamine, but it was mediated via PKA/CREB pathway only for Yueju. PMID:27197752

  7. PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine.

    PubMed

    Xue, Wenda; Wang, Wei; Gong, Tong; Zhang, Hailou; Tao, Weiwei; Xue, Lihong; Sun, Yan; Wang, Fushun; Chen, Gang

    2016-01-01

    Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju. One day post Yueju in Kunming but not ICR strain mice, expression of total and phosphorylated CREB, as well as the CREB signaling activator, PKA (protein kinase A) was up-regulated in the hippocampus. Although BDNF gene expression increased at 3 hours in both strains, it remained up-regulated at 1 day only in Kunming mice. Ketamine showed similar strain-dependent behavioral effects. However, blockade of PKA/CREB signaling blunted the antidepressant effects and reversed the up-regulation of BDNF gene expression by Yueju, but not ketamine. Conversely, blockade of mammalian target of rapamycin signaling led to opposite effects. Taken altogether, prolonged transcriptional up-regulation of hippocampal BDNF may account for the stain-dependent enduring antidepressant responses to Yueju and ketamine, but it was mediated via PKA/CREB pathway only for Yueju. PMID:27197752

  8. Long-lasting changes in the cochlear K+ recycling structures after acute energy failure.

    PubMed

    Takiguchi, Yoichiro; Sun, Guang-wei; Ogawa, Kaoru; Matsunaga, Tatsuo

    2013-01-01

    Fibrocytes in the cochlear lateral wall and spiral limbus play an important role in transporting K(+) and have the capacity of self-renewal. We showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3NP) caused hearing loss in a concentration-dependent manner, mainly due to degeneration of cochlear fibrocytes. We produced long-lasting profound cochlear damage in this model by modifying the 3NP administration protocol and observed morphological changes at 16 weeks after the administration. In the spiral ligament, severe degeneration of fibrocytes was observed in the basal turn, and the levels of the Na,K-ATPase alpha and beta1 subunits and of NKCC1 were decreased in these cells, whereas connexin 26 (Cx26) level increased in the type 1 fibrocytes adjacent to the stria vascularis. In the stria vascularis, levels of Kir4.1 and L-PGDS decreased. In the spiral limbus, severe degeneration of fibrocytes was observed in the middle and basal turns, but NKCC1 and Cx26 were still found in the center of the limbus in the middle turn. These results indicate long-lasting changes in the cochlear lateral wall and spiral limbus, which may compensate for damaged K(+) recycling and protect cells from ATP shortage. PMID:23827367

  9. Long-lasting anti-emetic effect of T-2328, a novel NK(1) antagonist.

    PubMed

    Watanabe, Yumi; Okamoto, Masahito; Ishii, Taketoshi; Takatsuka, Satomi; Taniguchi, Hiroyuki; Nagasaki, Masaaki; Saito, Akira

    2008-06-01

    The effect of T-2328 {2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride}, a novel tachykinin NK(1)-receptor antagonist, was examined on cisplatin-induced emesis in ferrets. Cisplatin induced acute emesis in 24 h and delayed emesis during 24 and 72 h, respectively. Ondansetron, a 5-HT(3) antagonist, almost completely blocked the acute emesis and transiently reduced the delayed emesis. In contrast, T-2328 elicited long-lasting anti-emetic effects on both acute and delayed phases by a single intravenous administration. Suppression of delayed emesis was not due to elimination of the acute phase because the delayed emesis was also suppressed by administration after the onset of delayed emesis. Persistent blockade of NK(1) receptors in the brain was demonstrated by inhibition of the NK(1) agonist-induced foot tapping response for over 24 h. An appreciable amount of T-2328 was present in the brain 32 and 72 h after the injection. The NK(1) agonist-induced contractions of isolated ileum in guinea pigs was antagonized with IC(50) values of 1.4 nM in an insurmountable manner. It is likely that T-2328 exerts the long-lasting anti-emetic effect by not only long-term presence in the brain but also its insurmountable inhibition of NK(1) receptors. PMID:18544900

  10. Long-lasting semantic interference effects in object naming are not necessarily conceptually mediated

    PubMed Central

    Riley, Emma; McMahon, Katie L.; de Zubicaray, Greig

    2015-01-01

    Long-lasting interference effects in picture naming are induced when objects are presented in categorically related contexts in both continuous and blocked cyclic paradigms. Less consistent context effects have been reported when the task is changed to semantic classification. Experiment 1 confirmed the recent finding of cumulative facilitation in the continuous paradigm with living/non-living superordinate categorization. To avoid a potential confound involving participants responding with the identical superordinate category in related contexts in the blocked cyclic paradigm, we devised a novel set of categorically related objects that also varied in terms of relative age – a core semantic type associated with the adjective word class across languages. Experiment 2 demonstrated the typical interference effect with these stimuli in basic level naming. In Experiment 3, using the identical blocked cyclic paradigm, we failed to observe semantic context effects when the same pictures were classified as younger–older. Overall, the results indicate the semantic context effects in the two paradigms do not share a common origin, with the effect in the continuous paradigm arising at the level of conceptual representations or in conceptual-to-lexical connections while the effect in the blocked cyclic paradigm most likely originates at a lexical level of representation. The implications of these findings for current accounts of long-lasting interference effects in spoken word production are discussed. PMID:25999892

  11. Peculiarities of transformation of adaptation level of the astronaut in conditions of long-lasting flight

    NASA Astrophysics Data System (ADS)

    Padashulya, H.; Prisnyakova, L.; Prisnyakov, V.

    Prognostication of the development of adverse factors of psychological processes in the personality of the astronaut who time and again feels transformation of internal structure of his personality is one of cardinal problems of the long-lasting flight Adaptation to changing conditions of long-lasting flight is of particular importance because it has an effect on the efficiency of discharged functions and mutual relations in the team The fact of standard psychological changes emerging in the personality being in the state of structural transformations is the precondition for the possibility of prognostication Age-specific gender and temperamental differences in the personality enable to standardize these changes Examination of the process of transformation of adaptation level of the personality in the varied environment depending on the type of temperament and constituents age and gender is chief object of the report In the report it is shown that in the process of transformation of adaptation parameters - attitude to guillemotleft work guillemotright guillemotleft family guillemotright guillemotleft environment guillemotright and guillemotleft ego guillemotright - the changes can go in two directions - in the direction of increase and decline of indexes The trend of increase enables to accumulate them and form potentiality to reduce or increase the level of personality adaptation There is a hypothesis that the dynamics of the process of transformation of adaptation parameter is shown up in the orientation of increase of

  12. α-Synuclein produces a long-lasting increase in neurotransmitter release

    PubMed Central

    Liu, Shumin; Ninan, Ipe; Antonova, Irina; Battaglia, Fortunato; Trinchese, Fabrizio; Narasanna, Archana; Kolodilov, Nikolai; Dauer, William; Hawkins, Robert D; Arancio, Ottavio

    2004-01-01

    Wild-type α-synuclein, a protein of unknown function, has received much attention because of its involvement in a series of diseases that are known as synucleinopathies. We find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of α-synuclein clusters. Conversely, suppression of α-synuclein expression through antisense nucleotide and knockout techniques blocks the potentiation, as well as the glutamate-induced increase in presynaptic functional bouton number. Consistent with these findings, α-synuclein introduction into the presynaptic neuron of a pair of monosynaptically connected cells causes a rapid and long-lasting enhancement of synaptic transmission, and rescues the block of potentiation in α-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of α-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of α-synuclein clusters. Thus, α-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal. PMID:15510220

  13. Bacterial Urease and its Role in Long-Lasting Human Diseases

    PubMed Central

    Konieczna, Iwona; Żarnowiec, Paulina; Kwinkowski, Marek; Kolesińska, Beata; Frączyk, Justyna; Kamiński, Zbigniew; Kaca, Wiesław

    2012-01-01

    Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. The presence of ureolytic activity is an important marker of a number of bacterial infections. Urease is also an immunogenic protein and is recognized by antibodies present in human sera. The presence of such antibodies is connected with progress of several long-lasting diseases, like rheumatoid arthritis, atherosclerosis or urinary tract infections. In bacterial ureases, motives with a sequence and/or structure similar to human proteins may occur. This phenomenon, known as molecular mimicry, leads to the appearance of autoantibodies, which take part in host molecules destruction. Detection of antibodies-binding motives (epitopes) in bacterial proteins is a complex process. However, organic chemistry tools, such as synthetic peptide libraries, are helpful in both, epitope mapping as well as in serologic investigations. In this review, we present a synthetic report on a molecular organization of bacterial ureases - genetic as well as structural. We characterize methods used in detecting urease and ureolytic activity, including techniques applied in disease diagnostic processes and in chemical synthesis of urease epitopes. The review also provides a summary of knowledge about a toxic effect of bacterial ureases on human body and about occurrence of anti-urease antibodies in long-lasting diseases. PMID:23305365

  14. Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage

    PubMed Central

    Tomaiuolo, Micol; Katche, Cynthia; Viola, Haydee; Medina, Jorge H.

    2015-01-01

    The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. PMID:26380116

  15. Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage.

    PubMed

    Tomaiuolo, Micol; Katche, Cynthia; Viola, Haydee; Medina, Jorge H

    2015-01-01

    The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. PMID:26380116

  16. Normal hearing is required for the emergence of long-lasting inhibitory potentiation in cortex

    PubMed Central

    Xu, Han; Kotak, Vibhakar C.; Sanes, Dan H.

    2010-01-01

    Long-term synaptic plasticity is a putative mechanism for learning in adults. However, there is little understanding of how synaptic plasticity mechanisms develop or whether their maturation depends on experience. Since inhibitory synapses are particularly malleable to sensory stimulation, long-lasting potentiation of inhibitory synapses was characterized in auditory thalamocortical slices. Intracortical high frequency electrical stimulation led to a 67% increase in inhibitory synaptic currents. In the absence of stimulation, inhibitory potentiation was induced by a brief exposure to exogenous BDNF. BDNF exposure occluded any further potentiation by high frequency afferent stimulation, suggesting that BDNF signaling is sufficient to account for inhibitory potentiation. Moreover, inhibitory potentiation was reduced significantly by extracellular application of a BDNF scavenger or by intracellular blockade of BDNF receptor (TrkB) signaling. In contrast, glutamatergic or GABAergic antagonists did not prevent the induction of inhibitory potentiation. Since BDNF and TrkB expression are influenced strongly by activity, we predicted that inhibitory potentiation would be diminished by manipulations that decrease central auditory activity, such as hearing loss. Two forms of hearing loss were examined: conductive hearing loss in which the cochleae are not damaged or sensorineural hearing loss in which both cochleae are removed. Both forms of hearing loss were found to reduce significantly the magnitude of inhibitory potentiation. These data indicate that early experience is necessary for the normal development of BDNF-mediated long-lasting inhibitory potentiation, which may be associated with perceptual deficits at later ages. PMID:20053914

  17. Tactile Stimulation Evokes Long-Lasting Potentiation of Purkinje Cell Discharge In Vivo

    PubMed Central

    Ramakrishnan, K. B.; Voges, Kai; De Propris, Licia; De Zeeuw, Chris I.; D’Angelo, Egidio

    2016-01-01

    In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in Purkinje cell (PC) spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here, we show that facial tactile stimuli organized in theta-patterns can induce stereotyped N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA-A) receptor-dependent changes in PCs and molecular layer interneurons (MLIs) firing: invariably, all PCs showed a long-lasting increase (Spike-Related Potentiation or SR-P) and MLIs a long-lasting decrease (Spike-Related Suppression or SR-S) in baseline activity and spike response probability. These observations suggests that tactile sensory stimulation engages multiple long-term plastic changes that are distributed along the mossy fiber-parallel fiber (MF-PF) pathway and operate synergistically to potentiate spike generation in PCs. In contrast, theta-pattern electrical stimulation (ES) of PFs indistinctly induced SR-P and SR-S both in PCs and MLIs, suggesting that tactile sensory stimulation preordinates plasticity upstream of the PF-PC synapse. All these effects occurred in the absence of complex spike changes, supporting the theoretical prediction that PC activity is potentiated when the MF-PF system is activated in the absence of conjunctive climbing fiber (CF) activity. PMID:26924961

  18. Biodegradable polyester-based microcarriers with modified surface tailored for tissue engineering.

    PubMed

    Privalova, A; Markvicheva, E; Sevrin, Ch; Drozdova, M; Kottgen, C; Gilbert, B; Ortiz, M; Grandfils, Ch

    2015-03-01

    Microcarriers have been proposed in tissue engineering, namely for bone, cartilage, skin, vascular, and central nervous system. Although polyester-based microcarriers have been already used for this purpose, their surface properties should be improved to provide better cell growth. The goal of this study was to prepare microbeads based on poly(D,L-lactide) acid, poly(L-lactide) acid, and to study cell behavior (adhesion, spreading, growth, and proliferation) in function of microbead topography and surface chemistry. To improve L-929 fibroblasts adhesion, microbead surface has been modified with three polycations: chitosan, poly(2-dimethylamino ethylmethacrylate) (PDMAEMA), or chitosan-g-oligolactide copolymer (chit-g-OLA). Although modification of the microbead surface with chitosan and PDMAEMA was performed through physical adsorption on the previously prepared microbeads, chit-g-OLA copolymer was introduced directly during microbead processing. This simple approach (1) bypass the use of an emulsifier (polyvinyl alcohol, PVA); (2) avoid surface "contamination" with PVA molecules limiting a control of the surface characteristics. In vitro study of the growth of mouse fibroblasts on the microbeads showed that both surface topography and chemistry affected cell attachment, spreading, and proliferation. Cultivation of L-929 fibroblasts for 7 days resulted in the formation of a 3D cell-scaffold network. PMID:24832052

  19. Two long-lasting central respiratory responses following acute hypoxia in glomectomized cats.

    PubMed

    Gallman, E A; Millhorn, D E

    1988-01-01

    1. Central respiratory response to acute (10 min) hypoxia, as measured by phrenic nerve activity, was determined in peripheral chemo-denervated cats. 2. Hypoxia was induced by ventilating cats for 10 min at reduced inspired oxygen levels (inspired O2 fraction, FI,O2 = 0.06-0.15). The degree of hypoxaemia was determined from an arterial blood sample and ranged from 'severe' (arterial O2 pressure, Pa,O2 less than 26 Torr) to 'mild' (Pa,O2 greater than 35 Torr). The respiratory response was monitored for 1 h following return to ventilation with 100% oxygen. 3. The results confirmed the finding of prolonged (greater than 60 min) inhibition of respiration upon return to hyperoxic conditions following severe hypoxia, as reported previously (Millhorn, Eldridge, Kiley & Waldrop, 1984). A new finding was a long-lasting (greater than 60 min) facilitation of respiration following exposure to less severe (Pa,O2 greater than 35 Torr) hypoxia. 4. Medullary extracellular fluid pH was measured in six cats. Changes in pH could not explain either the prolonged inhibition following severe hypoxia or the long-lasting facilitation observed following mild hypoxia. 5. Ablation studies were performed in order to determine the locations of the neuronal substrates for the inhibitory and facilitatory mechanisms. The results of this series of experiments indicate that the mesencephalon is necessary for activation of the inhibitory mechanism, while the facilitatory mechanism requires the presence of higher brain structures, notably the diencephalon. 6. Following removal of the diencephalon, the inhibitory response was seen following even mild hypoxic insults, i.e. those shown to produce facilitation in animals with intact brains. In the absence of the mesencephalon, neither prolonged inhibition nor prolonged facilitation could be produced following hypoxia. 7. It is proposed that there are two centrally mediated long-lasting responses to acute hypoxia. Facilitation is seen following mild

  20. Taurine-Induced Long-Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters

    PubMed Central

    Sergeeva, O A; Chepkova, A N; Doreulee, N; Eriksson, K S; Poelchen, W; Mönnighoff, I; Heller-Stilb, B; Warskulat, U; Häussinger, D; Haas, H L

    2003-01-01

    Taurine, a major osmolyte in the brain evokes a long-lasting enhancement (LLETAU) of synaptic transmission in hippocampal and cortico-striatal slices. Hippocampal LLETAU was abolished by the GABA uptake blocker nipecotic acid (NPA) but not by the taurine-uptake inhibitor guanidinoethyl sulphonate (GES). Striatal LLETAU was sensitive to GES but not to NPA. Semiquantitative PCR analysis and immunohistochemistry revealed that taurine transporter expression is significantly higher in the striatum than in the hippocampus. Taurine transporter-deficient mice displayed very low taurine levels in both structures and a low ability to develop LLETAU in the striatum, but not in the hippocampus. The different mechanisms of taurine-induced synaptic plasticity may reflect the different vulnerabilities of these brain regions under pathological conditions that are accompanied by osmotic changes such as hepatic encephalopathy. PMID:12824447

  1. Ephemeral disturbances have long-lasting impacts on forest invasion dynamics.

    PubMed

    Eschtruth, Anne K; Battles, John J

    2014-07-01

    Ephemeral disturbances are common in many systems. Often, these brief events are assumed to be a nuisance with little long-term ecological impact. We quantified the impact of the ephemeral forest disturbance caused by gypsy moth canopy defoliation on exotic plant invasion in eight hardwood forests in the Delaware Water Gap National Recreation Area, USA. Six years following the gypsy moth disturbance, we were able to predict 59% of the increase in Alliaria petiolata abundance and 42% of the increase in Microstegium vimineum abundance with models incorporating an interaction between disturbance severity and propagule pressure. In addition, we found that the disturbance timing had substantial impacts on the invasion dynamics of Alliaria petiolata. Our results suggest that ephemeral disturbances can have important and long-lasting impacts on plant communities, and highlight the need to account for variations in disturbance characteristics and the role of propagule pressure in determining the disturbance-invasion relationship. PMID:25163111

  2. Energetic ion excited long-lasting ``sword'' modes in tokamak plasmas with low magnetic shear

    NASA Astrophysics Data System (ADS)

    Wang, Xiaogang; Zhang, Ruibin; Deng, Wei; Liu, Yi

    2013-10-01

    An m/ n = 1 mode driven by trapped fast ions with a sword-shape envelope of long-lasting (for hundreds of milliseconds) magnetic perturbation signals, other than conventional fishbones, is studied in this paper. The mode is usually observed in low shear plasmas. Frequency and growth rate of the mode and its harmonics are calculated and in good agreements with observations. The radial mode structure is also obtained and compared with that of fishbones. It is found that due to fast ion driven the mode differs from magnetohydrodynamic long lived modes (LLMs) observed in MAST and NSTX. On the other hand, due to the feature of weak magnetic shear, the mode is also significantly different from fishbones. The nonlinear evolution of the mode and its comparison with fishbones are further investigated to analyze the effect of the mode on energetic particle transport and confinement.

  3. Prenatal exposure to LPS leads to long-lasting physiological consequences in male offspring.

    PubMed

    Asiaei, Masoud; Solati, Jalal; Salari, Ali-Akbar

    2011-12-01

    Growing evidence suggests that early life events are critical determinants for disorders later in life. According to a comprehensive number of epidemiological/animal studies, exposure to lipopolysaccharide, causes alteration in pro-inflammatory cytokine levels, hypothalamic-pituitary-adrenal functioning and the hormonal system which may contribute to behavioral and neurological injuries. In this study we investigated the effects of lipopolysaccharide administration on physiological parameters in pregnant dams and their male offspring aged 9 weeks. In gestational Day 10, pregnant mice were injected intrapritoneally with Salmonella enterica lipopolysaccharide to model prenatal exposure to infection. The following results were obtained for offspring from dams stressed during pregnancy: (a) reduced anxiety-related behavior in the elevated plus maze; (b) reduced food and water intake; (c) reduced body weight from birth up to postnatal Day 40. The observed data provide experimental evidence showing that prenatal stress can have complex and long-lasting physiological/behavioral consequences in offspring. PMID:21630247

  4. An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.

    PubMed

    Della Valle, M; Chincarini, G; Panagia, N; Tagliaferri, G; Malesani, D; Testa, V; Fugazza, D; Campana, S; Covino, S; Mangano, V; Antonelli, L A; D'Avanzo, P; Hurley, K; Mirabel, I F; Pellizza, L J; Piranomonte, S; Stella, L

    2006-12-21

    Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from the distant Universe. Long-duration GRBs (those lasting more than approximately 2 s) are believed to originate from the deaths of massive stars, mainly on the basis of a handful of solid associations between GRBs and supernovae. GRB 060614, one of the closest GRBs discovered, consisted of a 5-s hard spike followed by softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here we report deep optical observations of GRB 060614 showing no emerging supernova with absolute visual magnitude brighter than M(V) = -13.7. Any supernova associated with GRB 060614 was therefore at least 100 times fainter, at optical wavelengths, than the other supernovae associated with GRBs. This demonstrates that some long-lasting GRBs can either be associated with a very faint supernova or produced by different phenomena. PMID:17183317

  5. Human dignity as a component of a long-lasting and widespread conceptual construct.

    PubMed

    Baertschi, Bernard

    2014-06-01

    For some decades, the concept of human dignity has been widely discussed in bioethical literature. Some authors think that this concept is central to questions of respect for human beings, whereas others are very critical of it. It should be noted that, in these debates, dignity is one component of a long-lasting and widespread conceptual construct used to support a stance on the ethical question of the moral status of an action or being. This construct has been used from Modernity onward to condemn slavery and torture as violations of human dignity. In spelling it out, we can come to a better understanding of what "dignity" means and become aware that there exists a quite useful place for this notion in our ethical thought, albeit a modest one. PMID:24752523

  6. Long-lasting Localized Pemphigus Vulgaris without Detectable Serum Autoantibodies Against Desmoglein 3 and Desmoglein 1

    PubMed Central

    Yoshifuku, Asuka; Fujii, Kazuyasu; Kawahira, Hisao; Katsue, Hiromi; Baba, Atsunori; Higashi, Yuko; Aoyama, Yumi; Kanekura, Takuro

    2016-01-01

    Pemphigus vulgaris (PV) is an autoimmune blistering disease elicited by anti-desmoglein (DsG) 3 antibody. Although skin lesions tend to be distributed over the entire body, in some patients, they are confined to a restricted area. We report two patients who presented with long-lasting localized PV without detectable anti-DsG antibodies after suffering antibody-positive systemic PV. Initial treatment with prednisolone (PSL) was successful in both patients, but a local relapse occurred on the cheek or lower lip after a reduction in the PSL dose. Biopsy of the localized lesions showed suprabasal acantholysis; no serum DsG antibodies were found. Local immunosuppression therapy was effective in both patients. Based on our findings, we suggest that localized PV without detectable antibodies can develop after systemic PV. PMID:27512189

  7. An unusually long-lasting outbreak of community-acquired Legionnaires' disease, 2005-2008, Italy.

    PubMed

    Scaturro, M; Fontana, S; Crippa, S; Caporali, M G; Seyler, T; Veschetti, E; Villa, G; Rota, M C; Ricci, M L

    2015-08-01

    An unusually long-lasting community-acquired outbreak of Legionnaires' disease (LD) occurred in the inhabitants of a town in northern Italy from 2005 to 2008. Overall, 43 cases were diagnosed including five deaths. Hundreds of water samples were collected for Legionella isolation but only two clinical samples were obtained. Clinical strains were ST23 as were environmental isolates detected in most Legionella-positive patients' homes and those from a public fountain. Although no Legionella was found in the municipal water mains, a continuous chlorination was applied in 2008. This action resulted in a halving of cases, although incidence remained tenfold higher than the Italian average incidence until the end of 2013, when it dropped to the expected rate. Retrospective analyses of prevalent wind direction suggested that a hidden cooling tower could have been the main cause of this uncommon outbreak, highlighting the importance of implementation of cooling tower registers in supporting LD investigations. PMID:25427871

  8. Long-Lasting Reduction of Blood Pressure by Electroacupuncture in Patients with Hypertension: Randomized Controlled Trial

    PubMed Central

    Li, Peng; Cheng, Ling; Liu, Dongmei; Painovich, Jeannette; Vinjamury, Sivarama; Longhurst, John C.

    2015-01-01

    Abstract Background: Acupuncture at specific acupoints has experimentally been found to reduce chronically elevated blood pressure. Objective: To examine effectiveness of electroacupuncture (EA) at select acupoints to reduce systolic blood pressure (SBP) and diastolic blood pressures (DBP) in hypertensive patients. Design: Two-arm parallel study. Patients: Sixty-five hypertensive patients not receiving medication were assigned randomly to one of the two acupuncture intervention (33 versus 32 patients). Intervention: Patients were assessed with 24-hour ambulatory blood pressure monitoring. They were treated with 30-minutes of EA at PC 5-6+ST 36-37 or LI 6-7+GB 37-39 once weekly for 8 weeks. Four acupuncturists provided single-blinded treatment. Main outcome measures: Primary outcomes measuring effectiveness of EA were peak and average SBP and DBP. Secondary outcomes examined underlying mechanisms of acupuncture with plasma norepinephrine, renin, and aldosterone before and after 8 weeks of treatment. Outcomes were obtained by double-blinded evaluation. Results: After 8 weeks, 33 patients treated with EA at PC 5-6+ST 36-37 had decreased peak and average SBP and DBP, compared with 32 patients treated with EA at LI 6-7+GB 37-39 control acupoints. Changes in blood pressures significantly differed between the two patient groups. In 14 patients, a long-lasting blood pressure–lowering acupuncture effect was observed for an additional 4 weeks of EA at PC 5-6+ST 36-37. After treatment, the plasma concentration of norepinephrine, which was initially elevated, was decreased by 41%; likewise, renin was decreased by 67% and aldosterone by 22%. Conclusions: EA at select acupoints reduces blood pressure. Sympathetic and renin-aldosterone systems were likely related to the long-lasting EA actions. PMID:26392838

  9. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant.

    PubMed

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  10. Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation

    PubMed Central

    Toprani, Sheela; Durand, Dominique M

    2013-01-01

    Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease. Deep brain electrical stimulation (DBS) of grey matter has been used for MTLE with limited success. However, stimulation of a white matter tract connecting the hippocampi, the ventral hippocampal commissure (VHC), with low frequencies that simulate interictal discharges has shown promising results, with seizure reduction greater than 98% in bilateral hippocampi during stimulation and greater than 50% seizure reduction in bilateral hippocampi after treatment. A major hurdle to the implementation and optimization of this treatment is that the mechanisms of seizure reduction by low frequency electrical stimulation (LFS) are not known. The goal of this study is to understand how commissural fibre tract stimulation reduces bilateral hippocampal epileptic activity in an in vitro slice preparation containing bilateral hippocampi connected by the VHC. It is our hypothesis that electrical stimuli induce hyperpolarization lasting hundreds of milliseconds following each pulse which reduces spontaneous epileptic activity during each inter-stimulus interval (ISI). Stimulus-induced long-lasting-hyperpolarization (LLH) can be mediated by GABAB inhibitory post-synaptic potentials (IPSPs) or slow after-hyperpolarization (sAHP). To test the role of LLH in effective bilateral seizure reduction by fibre tract stimulation, we measured stimulus-induced hyperpolarization during LFS of the VHC using electrophysiology techniques. Antagonism of the GABAB IPSP and/or sAHP diminished stimulus-induced hyperpolarization concurrently with LFS efficacy (greater than 50% reduction). Blocking both the GABAB IPSP and sAHP simultaneously eliminated the effect of electrical stimulation on seizure reduction entirely. These data show that LFS of the VHC is an effective protocol for bilateral hippocampal seizure reduction and that its efficacy relies on the induction of long-lasting hyperpolarization mediated

  11. Neuropeptide Y Gates a Stress-Induced, Long-Lasting Plasticity in the Sympathetic Nervous System

    PubMed Central

    Wang, Qian; Wang, Manqi

    2013-01-01

    Acute stress evokes the fight-or-flight reflex, which via release of the catecholamine hormones affects the function of every major organ. Although the reflex is transient, it has lasting consequences that produce an exaggerated response when stress is reexperienced. How this change is encoded is not known. We investigated whether the reflex affects the adrenal component of the sympathetic nervous system, a major branch of the stress response. Mice were briefly exposed to the cold-water forced swim test (FST) which evoked an increase in circulating catecholamines. Although this hormonal response was transient, the FST led to a long-lasting increase in the catecholamine secretory capacity measured amperometrically from chromaffin cells and in the expression of tyrosine hydroxylase. A variety of approaches indicate that these changes are regulated postsynaptically by neuropeptide Y (NPY), an adrenal cotransmitter. Using immunohistochemistry, RT-PCR, and NPY(GFP) BAC mice, we find that NPY is synthesized by all chromaffin cells. Stress failed to increase secretory capacity in NPY knock-out mice. Genetic or pharmacological interference with NPY and Y1 (but not Y2 or Y5) receptor signaling attenuated the stress-induced change in tyrosine hydroxylase expression. These results indicate that, under basal conditions, adrenal signaling is tonically inhibited by NPY, but stress overrides this autocrine negative feedback loop. Because acute stress leads to a lasting increase in secretory capacity in vivo but does not alter sympathetic tone, these postsynaptic changes appear to be an adaptive response. We conclude that the sympathetic limb of the stress response exhibits an activity-dependent form of long-lasting plasticity. PMID:23904607

  12. Long-lasting corneal endothelial graft rejection successfully reversed after dexamethasone intravitreal implant

    PubMed Central

    Giannaccare, Giuseppe; Fresina, Michela; Pazzaglia, Alberto; Versura, Piera

    2016-01-01

    Graft rejection is the most significant complication corneal transplantation and the leading indication for overall corneal transplantation. Corticosteroid therapy represents the mainstay of graft rejection treatment; however, the optimal route of administration of corticosteroid remains uncertain. We report herein for the first time the multimodal imaging of a case of long-lasting corneal endothelial graft rejection successfully reversed 3 months after dexamethasone intravitreal implant. A 29-year-old Asian female presented with a long-lasting corneal endothelial graft rejection in her left phakic eye. She underwent penetrating keratoplasty for advanced keratoconus 24 months before presentation. Hourly dexamethasone eyedrops, daily intravenous methylprednisolone, and one parabulbar injection of methylprednisolone acetate were administered during the 5 days of hospitalization. However, the clinical picture remained approximately unchanged despite therapy. By mutual agreement, we opted for the off-label injection of dexamethasone 0.7 mg intravitreal implant in order to provide therapeutic concentrations of steroid for a period of ~6 months. No other concomitant therapies were prescribed to the patient. Visual acuity measurement, slit lamp biomicroscopy, anterior segment photography, confocal microscopy, anterior segment optical coherence tomography, laser cell flare meter, intraocular pressure measurement, and ophthalmoscopy were performed monthly for the first postoperative 6 months. Three months after injection, both clinical and subclinical signs of rejection disappeared with a full recovery of visual acuity to 20/30 as before the episode. Currently, at the 12-month follow-up visit, the clinical picture remains stable without any sign of rejection, recurrence, or graft failure. Dexamethasone intravitreal implant seems to be a new potential effective treatment for corneal graft rejection, particularly in case of poor compliance or lack of response to conventional

  13. NOVAE WITH LONG-LASTING SUPERSOFT EMISSION THAT DRIVE A HIGH ACCRETION RATE

    SciTech Connect

    Schaefer, Bradley E.; Collazzi, Andrew C.

    2010-05-15

    We identify a new class of novae characterized by the post-eruption quiescent light curve being more than roughly a factor of 10 brighter than the pre-eruption light curve. Eight novae (V723 Cas, V1500 Cyg, V1974 Cyg, GQ Mus, CP Pup, T Pyx, V4633 Sgr, and RW UMi) are separated out as being significantly distinct from other novae. This group shares a suite of uncommon properties, characterized by the post-eruption magnitude being much brighter than before eruption, short orbital periods, long-lasting supersoft emission following the eruption, a highly magnetized white dwarf (WD), and secular declines during the post-eruption quiescence. We present a basic physical picture which shows why all five uncommon properties are causally connected. In general, novae show supersoft emission due to hydrogen burning on the WD in the final portion of the eruption, and this hydrogen burning will be long-lasting if new hydrogen is poured onto the surface at a sufficient rate. Most novae do not have adequate accretion for continuous hydrogen burning, but some can achieve this if the companion star is nearby (with short orbital period) and a magnetic field channels the matter onto a small area on the WD so as to produce a locally high accretion rate. The resultant supersoft flux irradiates the companion star and drives a higher accretion rate (with a brighter post-eruption phase), which serves to keep the hydrogen burning and the supersoft flux going. The feedback loop cannot be perfectly self-sustaining, so the supersoft flux will decline over time, forcing a decline in the accretion rate and the system brightness. We name this new group after the prototype, V1500 Cyg. V1500 Cyg stars are definitely not progenitors of Type Ia supernovae. The V1500 Cyg stars have similar physical mechanisms and appearances as predicted for nova by the hibernation model, but with this group accounting for only 14% of novae.

  14. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors.

    PubMed

    Bales, K L; Plotsky, P M; Young, L J; Lim, M M; Grotte, N; Ferrer, E; Carter, C S

    2007-01-01

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations. PMID:17055176

  15. White-light-emitting long-lasting phosphorescence in Dy{sup 3+}-doped SrSiO{sub 3}

    SciTech Connect

    Kuang Jinyong; Liu Yingliang . E-mail: tliuyl@jnu.edu.cn; Zhang Jianxian

    2006-01-15

    We report on a luminescent phenomenon in Dy{sup 3+}-doped SrSiO{sub 3} long-lasting phosphor. After irradiation by a 254-nm UV lamp for 5min, the Dy{sup 3+}-doped SrSiO{sub 3} phosphor emits white light-emitting long-lasting phosphorescence for more than 1h even after the irradiation source has been removed. Photoluminescence, long-lasting phosphorescence and thermoluminescence (TL) spectra are used to explain this phenomenon. Photoluminescence spectra reveal that the white light-emitting long-lasting phosphorescence originated from the two mixtures of Dy{sup 3+} characteristic luminescence, the 480-nm blue emission ({sup 4}F{sub 9/2}->{sup 6}H{sub 15/2}) and the 572-nm yellow emission ({sup 4}F{sub 9/2}->{sup 6}H{sub 13/2}). TL spectra shows that the introduction of Dy{sup 3+} ions into the SrSiO{sub 3} host produces a highly dense trapping level at 377K (0.59eV), which is responsible for the long-lasting phosphorescence at room temperature. A possible mechanism of the long-lasting phosphorescence based on the experimental results is proposed. It is considered that the long-lasting phosphorescence is due to persistent energy transfer from the electron traps to the Dy{sup 3+} ions, which creates the persistent luminescence of Dy{sup 3+} to produce the white light-emitting long-lasting phosphorescence.

  16. Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

    SciTech Connect

    Lundstedt, Dan; Gustafsson, Magnus; Steineck, Gunnar; Malmstroem, Per; Alsadius, David; Sundberg, Agnetha; Wilderaeng, Ulrica; Holmberg, Erik; Johansson, Karl-Axel; Karlsson, Per

    2012-05-01

    Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting

  17. Did the short PETM trigger long-lasting changes in terrestrial environments?

    NASA Astrophysics Data System (ADS)

    Fricke, H. C.; Clyde, W. C.

    2012-12-01

    The Paleocene Eocene Thermal Maximum (PETM) is a well-documented episode of warming where average temperatures increased 5-8 C in both marine and terrestrial settings before returning to pre-PETM values. As a result the PETM is generally thought of as a transient event that is superimposed on a longer-term trend of global change. Nevertheless not all aspects of the climatic-hydrologic-biologic system experienced a transient response to this event. For example, the well-known dispersal of mammals (Artiodactyls, Perrisopdactyls and Primates = APP taxa) at the beginning of the PETM resulted in fundamentally different terrestrial ecosystems dafter the PETM compared to before it. In this case the PETM can be considered not just a transient event, but a triggering, or threshold, event that resulted in long-term biotic change. Here we consider the possibility that the PETM acted as a threshold event for parts of the climatic and hydrologic system as well as the biologic system. A review of terrestrial/fluvial sections from Laramide basins of western North America (Bighorn, Green River, Huerfano/Raton, Piceance Creek, Powder River, San Juan, Tornillo, Uintah, Washakie, Williston, Wind River), reveals a pronounced difference between rocks of Paleocene and of Eocene age. Common differences include absence of lignites/coal beds in the Eocene, and the occurrence of highly oxidized paleosols and relatively fewer organic-rich mudstones compared to the Paleocene. These suggest drier conditions, either a decrease in mean annual precipitation or enhanced seasonal drying. In sections where the PETM can be identified on the basis of biostratigraphic indicators and carbon isotope excursions (Bighorn, Piceance Creek, Powder River and Williston Basins), and where the PETM can be inferred based on carbon isotope data alone (Huerfano/Raton?, Tornillo, Wind River Basins), it is associated with this transition from one long-lasting lithofacies (environment?) to another. This association

  18. Tonotopic and Field-Specific Representation of Long-Lasting Sustained Activity in Rat Auditory Cortex.

    PubMed

    Shiramatsu, Tomoyo I; Noda, Takahiro; Akutsu, Kan; Takahashi, Hirokazu

    2016-01-01

    Cortical information processing of the onset, offset, and continuous plateau of an acoustic stimulus should play an important role in acoustic object perception. To date, transient activities responding to the onset and offset of a sound have been well investigated and cortical subfields and topographic representation in these subfields, such as place code of sound frequency, have been well characterized. However, whether these cortical subfields with tonotopic representation are inherited in the sustained activities that follow transient activities and persist during the presentation of a long-lasting stimulus remains unknown, because sustained activities do not exhibit distinct, reproducible, and time-locked responses in their amplitude to be characterized by grand averaging. To address this gap in understanding, we attempted to decode sound information from densely mapped sustained activities in the rat auditory cortex using a sparse parameter estimation method called sparse logistic regression (SLR), and investigated whether and how these activities represent sound information. A microelectrode array with a grid of 10 × 10 recording sites within an area of 4.0 mm × 4.0 mm was implanted in the fourth layer of the auditory cortex in rats under isoflurane anesthesia. Sustained activities in response to long-lasting constant pure tones were recorded. SLR then was applied to discriminate the sound-induced band-specific power or phase-locking value from those of spontaneous activities. The highest decoding performance was achieved in the high-gamma band, indicating that cortical inhibitory interneurons may contribute to the sparse tonotopic representation in sustained activities by mediating synchronous activities. The estimated parameter in the SLR decoding revealed that the informative recording site had a characteristic frequency close to the test frequency. In addition, decoding of the four test frequencies demonstrated that the decoding performance of the SLR

  19. Tonotopic and Field-Specific Representation of Long-Lasting Sustained Activity in Rat Auditory Cortex

    PubMed Central

    Shiramatsu, Tomoyo I.; Noda, Takahiro; Akutsu, Kan; Takahashi, Hirokazu

    2016-01-01

    Cortical information processing of the onset, offset, and continuous plateau of an acoustic stimulus should play an important role in acoustic object perception. To date, transient activities responding to the onset and offset of a sound have been well investigated and cortical subfields and topographic representation in these subfields, such as place code of sound frequency, have been well characterized. However, whether these cortical subfields with tonotopic representation are inherited in the sustained activities that follow transient activities and persist during the presentation of a long-lasting stimulus remains unknown, because sustained activities do not exhibit distinct, reproducible, and time-locked responses in their amplitude to be characterized by grand averaging. To address this gap in understanding, we attempted to decode sound information from densely mapped sustained activities in the rat auditory cortex using a sparse parameter estimation method called sparse logistic regression (SLR), and investigated whether and how these activities represent sound information. A microelectrode array with a grid of 10 × 10 recording sites within an area of 4.0 mm × 4.0 mm was implanted in the fourth layer of the auditory cortex in rats under isoflurane anesthesia. Sustained activities in response to long-lasting constant pure tones were recorded. SLR then was applied to discriminate the sound-induced band-specific power or phase-locking value from those of spontaneous activities. The highest decoding performance was achieved in the high-gamma band, indicating that cortical inhibitory interneurons may contribute to the sparse tonotopic representation in sustained activities by mediating synchronous activities. The estimated parameter in the SLR decoding revealed that the informative recording site had a characteristic frequency close to the test frequency. In addition, decoding of the four test frequencies demonstrated that the decoding performance of the SLR

  20. Long-Lasting Gene Conversion Shapes the Convergent Evolution of the Critical Methanogenesis Genes

    PubMed Central

    Wang, Sishuo; Chen, Youhua; Cao, Qinhong; Lou, Huiqiang

    2015-01-01

    Methanogenesis and its key small-molecule methyltransferase Mtr complex are poorly understood despite their pivotal role in Earth’s global carbon cycle. Mtr complex is encoded by a conserved mtrEDCBAFGH operon in most methanogens. Here we report that two discrete lineages, Methanococcales and Methanomicrobiales, have a noncanonical mtr operon carrying two copies of mtrA resulting from an ancient duplication. Compared to mtrA-1, mtrA-2 acquires a distinct transmembrane domain through domain shuffling and gene fusion. However, the nontransmembrane domains (MtrA domain) of mtrA-1 and mtrA-2 are homogenized by gene conversion events lasting throughout the long history of these extant methanogens (over 2410 million years). Furthermore, we identified a possible recruitment of ancient nonmethanogenic methyltransferase genes to establish the methanogenesis pathway. These results not only provide novel evolutionary insight into the methanogenesis pathway and methyltransferase superfamily but also suggest an unanticipated long-lasting effect of gene conversion on gene evolution in a convergent pattern. PMID:26384370

  1. Multisatellite Observations of Long-lasting Poloidal Pc 4 Pulsations in the Dayside Magnetosphere.

    NASA Astrophysics Data System (ADS)

    Sibeck, D. G.; Korotova, G. I.; Engebretson, M. J.; Wygant, J. R.; Thaller, S. A.

    2015-12-01

    We use magnetic field, plasma and particles observations from Van Allen Probes and THEMIS spacecraft to study the characteristics of long-lasting poloidal Pc4 pulsations in the dayside magnetosphere. They were observed after the main phase of a strong storm during low geomagnetic activity. The Pc 4 pulsations exhibited periods of 40-50 s and amplitudes of 4-6 nT in the dominant radial component. They had a packet-like structure and lasted more than 3 hours. The FFT spectra show that the main spectral power corresponds to frequencies of ~ 20-22 mHz, which argues against a source for the pulsations in the solar wind. The frequencies of the central power peak in the radial component decrease with radial distance from the Earth. The most striking feature of the Pc 4 pulsations was their occurrence at similar locations on three of four successive orbits of Van Allen Probes nine hours apart. We determined that the pulsations were second harmonic mode waves. We test various possible mechanisms for their generation.

  2. Spinal adenosine A2a receptor activation elicits long-lasting phrenic motor facilitation.

    PubMed

    Golder, Francis J; Ranganathan, Lavanya; Satriotomo, Irawan; Hoffman, Michael; Lovett-Barr, Mary Rachael; Watters, Jyoti J; Baker-Herman, Tracy L; Mitchell, Gordon S

    2008-02-27

    Acute intermittent hypoxia elicits a form of spinal, brain-derived neurotrophic factor (BDNF)-dependent respiratory plasticity known as phrenic long-term facilitation. Ligands that activate G(s)-protein-coupled receptors, such as the adenosine 2a receptor, mimic the effects of neurotrophins in vitro by transactivating their high-affinity receptor tyrosine kinases, the Trk receptors. Thus, we hypothesized that A2a receptor agonists would elicit phrenic long-term facilitation by mimicking the effects of BDNF on TrkB receptors. Here we demonstrate that spinal A2a receptor agonists transactivate TrkB receptors in the rat cervical spinal cord near phrenic motoneurons, thus inducing long-lasting (hours) phrenic motor facilitation. A2a receptor activation increased phosphorylation and new synthesis of an immature TrkB protein, induced TrkB signaling through Akt, and strengthened synaptic pathways to phrenic motoneurons. RNA interference targeting TrkB mRNA demonstrated that new TrkB protein synthesis is necessary for A2a-induced phrenic motor facilitation. A2a receptor activation also increased breathing in unanesthetized rats, and improved breathing in rats with cervical spinal injuries. Thus, small, highly permeable drugs (such as adenosine receptor agonists) that transactivate TrkB receptors may provide an effective therapeutic strategy in the treatment of patients with ventilatory control disorders, such as obstructive sleep apnea, or respiratory insufficiency after spinal injury or during neurodegenerative diseases. PMID:18305238

  3. Electronic signatures for long-lasting storage purposes in electronic archives.

    PubMed

    Pharow, Peter; Blobel, Bernd

    2005-03-01

    Communication and co-operation in healthcare and welfare require a certain set of trusted third party (TTP) services describing both status and relation of communicating principals as well as their corresponding keys and attributes. Additional TTP services are needed to provide trustworthy information about dynamic issues of communication and co-operation such as time and location of processes, workflow relations, and system behaviour. Legal and ethical requirements demand securely stored patient information and well-defined access rights. Among others, electronic signatures based on asymmetric cryptography are important means for securing the integrity of a message or file as well as for accountability purposes including non-repudiation of both origin and receipt. Electronic signatures along with certified time stamps or time signatures are especially important for electronic archives in general, electronic health records (EHR) in particular, and especially for typical purposes of long-lasting storage. Apart from technical storage problems (e.g. lifetime of the storage devices, interoperability of retrieval and presentation software), this paper identifies mechanisms of e.g. re-signing and re-stamping of data items, files, messages, sets of archived items or documents, archive structures, and even whole archives. PMID:15694634

  4. Long lasting clinical response to chemotherapy for advanced uterine leiomyosarcoma: a case report

    PubMed Central

    2013-01-01

    Introduction Uterine leiomyosarcoma is one of the most frequent uterine sarcomas. In the metastatic setting it is sensitive to doxorubicin, ifosfamide, gemcitabine, docetaxel and a few other drugs, but time to progression is generally short. For this reason prognosis is often poor and there are few reports in the literature of long responders. Case presentation We report a case of a 40-year-old Caucasian woman with metastatic uterine leiomyosarcoma who began treatment six years before the presentation of this case report and for the following six years underwent ten lines of chemotherapy, achieving excellent results and a good quality of life. Among the treatments administered we observed a long response to temolozomide, an unconventional drug for this kind of disease. Conclusion Although there are few chemotherapeutic options for the management of metastatic uterine leiomyosarcoma, a small number of patients have an unexpected long lasting response to treatment. For this reason further research is needed to identify new therapeutic agents and the predictive factors for the achievement of response. PMID:23347560

  5. Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster.

    PubMed

    Trannoy, Séverine; Penn, Jill; Lucey, Kenia; Popovic, David; Kravitz, Edward A

    2016-04-26

    In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters. PMID:27071097

  6. Nongassing long-lasting electro-osmotic pump with polyaniline-wrapped aminated graphene electrodes.

    PubMed

    Kumar, Rudra; Jahan, Kousar; Nagarale, Rajaram K; Sharma, Ashutosh

    2015-01-14

    An efficient nongassing electro-osmotic pump (EOP) with long-lasting electrodes and exceptionally stable operation is developed by using novel flow-through polyaniline (PANI)-wrapped aminated graphene (NH2-G) electrodes. The NH2-G/PANI electrode combines the excellent oxidation/reduction capacity of PANI with the exceptional conductivity and inertness of NH2-G. The flow rate varies linearly with voltage but is highly dependent on the electrode composition. The flow rates at a potential of 5 V for pristine NH2-G and PANI electrodes are 71 and 100 μL min(-1) cm(-2), respectively, which increase substantially by the use of NH2-G/PANI electrode. It increased from 125 to 182 μL min(-1) cm(-2) as the fraction of aniline increased from 66.63 to 90.90%. The maximum flux obtained is 40 μL min(-1) V(-1) cm(-2) with NH2-G/PANI-90.9 electrodes. The assembled EOP remained exceptionally stable until the electrode columbic capacity was fully utilized. The prototype shown here delivered 8.0 μL/min at a constant applied voltage of 2 V for over 7 h of continuous operation. The best EOP produces a maximum stall pressure of 3.5 kPa at 3 V. These characteristics make it suitable for a variety of microfluidic/device applications. PMID:25478894

  7. Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone

    SciTech Connect

    Pang, P.K.T.; Wang, R.; Shan, J.; Karpinski, E.; Benishin, C.G. )

    1990-01-01

    The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.

  8. Long-lasting regulation of hippocampal Bdnf gene transcription after contextual fear conditioning.

    PubMed

    Mizuno, K; Dempster, E; Mill, J; Giese, K P

    2012-08-01

    Long-term memory formation requires de novo protein synthesis and gene transcription. During contextual long-term memory formation brain-derived neurotrophic factor (BDNF) gene expression changes in conjunction with alterations of DNA methylation in the Bdnf gene. However, little is known about the molecular mechanisms underlying the maintenance and persistence of contextual long-term memory. Here, we examined the transcription of specific Bdnf exons in the hippocampus for long periods after contextual fear conditioning. We found changes in transcription lasting for at least 24 h after contextual fear conditioning, with some sex-specific effects. In addition, hypomethylation at a CpG site in CpG island 2 located at the end of Bdnf exon III sequence was detected at 0.5 h and maintained for up to 24 h after contextual fear conditioning. The identification of these long-lasting changes in transcription and DNA methylation at the Bdnf gene suggests that BDNF might have a role for storage of contextual long-term memory in the hippocampus. PMID:22574690

  9. Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects

    PubMed Central

    Liu, Chen; Fu, Xuekun; Pan, Haobo; Wan, Peng; Wang, Lei; Tan, Lili; Wang, Kehong; Zhao, Ying; Yang, Ke; Chu, Paul K.

    2016-01-01

    A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications. PMID:27271057

  10. Neural representation of navigational relevance is rapidly induced and long lasting.

    PubMed

    Janzen, Gabriele; Wagensveld, Barbara; van Turennout, Miranda

    2007-04-01

    Successful navigation is facilitated by the presence of landmarks. Previous functional magnetic resonance imaging (fMRI) evidence indicated that the human parahippocampal gyrus automatically distinguishes between landmarks placed at navigationally relevant (decision points) and irrelevant locations (nondecision points). This storage of navigational relevance can provide a neural mechanism underlying successful navigation. However, an efficient wayfinding mechanism requires that important spatial information is learned quickly and maintained over time. The present study investigates whether the representation of navigational relevance is modulated by time and practice. Participants learned 2 film sequences through virtual mazes containing objects at decision and at nondecision points. One maze was shown one time, and the other maze was shown 3 times. Twenty-four hours after study, event-related fMRI data were acquired during recognition of the objects. The results showed that activity in the parahippocampal gyrus was increased for objects previously placed at decision points as compared with objects placed at nondecision points. The decision point effect was not modulated by the number of exposures to the mazes and independent of explicit memory functions. These findings suggest a persistent representation of navigationally relevant information, which is stable after only one exposure to an environment. These rapidly induced and long-lasting changes in object representation provide a basis for successful wayfinding. PMID:16751297

  11. Lynx reproduction--long-lasting life cycle of corpora lutea in a feline species.

    PubMed

    Jewgenow, Katarina; Painer, Johanna; Amelkina, Olga; Dehnhard, Martin; Goeritz, Frank

    2014-04-01

    A review of lynxes' reproductive biology and comparison between the reproductive cycles of the domestic cat and lynxes is presented. Three of the four lynx species (the bobcat excluded) express quite similar reproductive pattern (age at sexual maturity, estrus and pregnancy length, litter size). Similarly to the domestic cat, the bobcat is polyestric and can have more than one litter per year. Domestic cats and many other felid species are known to express anovulatory, pregnant and pseudo-pregnant reproductive cycles in dependence on ovulation induction and fertilization. The formation of corpora lutea (CLs) occurs after ovulation. In pregnant animals, luteal function ends with parturition, whereas during pseudo-pregnancy a shorter life span and lower hormone secretion are observed. The life cycle of corpora lutea in Eurasian lynxes is different from the pattern described in domestic cats. Lynx CLs produce progestagens in distinctive amounts permanently for at least two years, regardless of their origin (pregnancy or pseudo-pregnancy). It is suggested that long-lasting CLs induce a negative feedback to inactivate folliculogenesis, turning a normally polyestric cycle observed in most felids into a monoestric cycle in lynxes. PMID:24856466

  12. Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects.

    PubMed

    Liu, Chen; Fu, Xuekun; Pan, Haobo; Wan, Peng; Wang, Lei; Tan, Lili; Wang, Kehong; Zhao, Ying; Yang, Ke; Chu, Paul K

    2016-01-01

    A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications. PMID:27271057

  13. Evaluation of the long-lasting antihypertensive action of 7-O-ethylfangchinoline.

    PubMed

    Kato, T; Noguchi, K; Sakanashi, M

    1994-09-01

    The antihypertensive effect of 7-O-ethylfangchinoline (TJN-220) was analyzed in an experimental model of hypertensive rats under the conscious condition. Single oral administration of TJN-220 (25 and 50 mg/kg) produced a progressive and long-lasting fall of mean blood pressure in spontaneously hypertensive rats (SHRs), deoxycorticosterone acetate (DOCA)-salt hypertensive rats and renal hypertensive rats until 72 hr after the drug administration, but affected neither the heart rate in these hypertensive rats nor the hemodynamic parameters in normotensive rats. In SHRs implanted with a telemetry transmitter, TJN-220 (50 mg/kg, p.o.) produced falls of systolic and diastolic blood pressures and diminished the difference in blood pressure between the dark period and the light period for 3 days, particularly by suppressing the increasing phase of blood pressure during the dark period without influencing heart rate or locomotor activity. On the other hand, nicardipine (10 mg/kg, p.o.) produced a transient fall of blood pressure associated with a tachycardia during the light period on the first day alone. Clonidine (0.3 mg/kg, p.o.) diminished the increasing phases of blood pressure and heart rate during the dark period on the first day alone. Thus, the antihypertensive action of TJN-220 was much longer than those of nicardipine and clonidine. The present results suggest that TJN-220 may have potential for use as a beneficial antihypertensive drug. PMID:7861666

  14. Chronic sleep restriction during development can lead to long-lasting behavioral effects.

    PubMed

    Saré, R Michelle; Levine, Merlin; Hildreth, Christine; Picchioni, Dante; Smith, Carolyn Beebe

    2016-03-01

    Sleep abnormalities are highly correlated with neurodevelopmental disorders, and the severity of behavioral abnormalities correlates with the presence of sleep abnormalities. Given the importance of sleep in developmental plasticity, we sought to determine the effects of chronic sleep-restriction during development on subsequent adult behavior. We sleep-restricted developing wild-type mice from P5-P42 for 3h per day by means of gentle handling (n=30) and compared behavioral outputs to controls that were handled 10 min daily (n=33). We assayed activity in the open field, social behavior, repetitive behavior, and anxiety immediately following sleep restriction and after four weeks of recovery. At six weeks of age, immediately following chronic sleep-restriction, mice were less active in an open field arena. Sociability was increased, but repetitive behaviors were unchanged in both males and females. After a 4-week period of recovery, some behavioral abnormalities persisted and some became apparent. Sleep-restricted mice had decreased activity in the beginning of an open field test. Female mice continued to have increased sociability and, in addition, increased preference for social novelty. In contrast, male mice demonstrated decreased sociability with medium effect sizes. Repetitive behavior was decreased in sleep-restricted female mice and increased in males. Measures of anxiety were not affected in the sleep-restricted mice. These results indicate that chronic sleep restriction during development can lead to long-lasting behavioral changes that are modulated by sex. Our study may have implications for a role of disrupted sleep in childhood on the unfolding of neurodevelopmental disorders. PMID:26712276

  15. DNA shuffling: induced molecular breeding to produce new generation long-lasting vaccines.

    PubMed

    Marshall, Sergio H

    2002-11-01

    The paradigm for classic vaccines has been to mimic natural infection, and their success relies mostly on the induction of neutralizing antibodies followed by long-lasting immunity. The outcome of aggressive chronic infections such as HIV and HCV, the reappearance of fastidious diseases such as tuberculosis and the progression of cancer growth suggest that natural immune responses are definitely insufficient in many cases. A new paradigm is needed to design and develop a new high-efficiency generation of vaccines ideally able to surpass the capabilities of natural immune responses. In vitro evolution is a new, important laboratory method to evolve molecules with desired properties, which appears as an appealing alternative to achieve this goal. In its battle against disease, the vertebrate immune system triggers a series of well-known molecular events in order to produce protective neutralizing antibodies. This natural in vivo response shares remarkable similarities with the in vitro technique known as molecular breeding or "DNA shuffling." This method exploits the recombination between genes to dramatically accelerate the rate at which genes can be evolved under selection pressure in the laboratory, producing optimized high-efficiency mutant proteins. Since new generation vaccines are aimed to overcome natural selection and environmental pressures to fully inactivate rapidly developing pathogen variants, they could be engineered, developed and selected through the application of directed DNA shuffling procedures. This review highlights the potential of the procedure in the complex context of natural immune responses and the equilibrium and interaction existing in nature between hosts and pathogens. PMID:14550030

  16. Long-lasting effects of maternal condition in free-ranging cervids.

    PubMed

    Freeman, Eric D; Larsen, Randy T; Clegg, Ken; McMillan, Brock R

    2013-01-01

    Causes of phenotypic variation are fundamental to evolutionary ecology because they influence the traits acted upon by natural selection. One such cause of phenotypic variation is a maternal effect, which is the influence of the environment experienced by a female (and her corresponding phenotype) on the phenotype of her offspring (independent of the offspring's genotype). While maternal effects are well documented, the longevity and fitness impact of these effects remains unclear because it is difficult to follow free-living individuals through their reproductive lifetimes. For long-lived species, it has been suggested that maternal effects are masked by environmental variables acting on offspring in years following the period of dependence. Our objective was to use indirect measures of maternal condition to determine if maternal effects have long-lasting influences on male offspring in two species of cervid. Because antlers are sexually selected, we used measures of antler size at time of death, 1.5-21.5 years after gestation to investigate maternal effects. We quantified antler size of 11,000 male elk and mule deer born throughout the intermountain western US (6 states) over nearly 30 years. Maternal condition during development was estimated indirectly using a suite of abiotic variables known to influence condition of cervids (i.e., winter severity, spring and summer temperature, and spring and summer precipitation). Antler size of male cervids was significantly associated with our indirect measure of maternal condition during gestation and lactation. Assuming the correctness of our indirect measure, our findings demonstrate that antler size is a sexually selected trait that is influenced-into adulthood-by maternal condition. This link emphasizes the importance of considering inherited environmental effects when interpreting population dynamics or examining reproductive success of long-lived organisms. PMID:23472189

  17. The inhibitory neurotransmitter GABA evokes long-lasting Ca(2+) oscillations in cortical astrocytes.

    PubMed

    Mariotti, Letizia; Losi, Gabriele; Sessolo, Michele; Marcon, Iacopo; Carmignoto, Giorgio

    2016-03-01

    Studies over the last decade provided evidence that in a dynamic interaction with neurons glial cell astrocytes contribut to fundamental phenomena in the brain. Most of the knowledge on this derives, however, from studies monitoring the astrocyte Ca(2+) response to glutamate. Whether astrocytes can similarly respond to other neurotransmitters, including the inhibitory neurotransmitter GABA, is relatively unexplored. By using confocal and two photon laser-scanning microscopy the astrocyte response to GABA in the mouse somatosensory and temporal cortex was studied. In slices from developing (P15-20) and adult (P30-60) mice, it was found that in a subpopulation of astrocytes GABA evoked somatic Ca(2+) oscillations. This response was mediated by GABAB receptors and involved both Gi/o protein and inositol 1,4,5-trisphosphate (IP3 ) signalling pathways. In vivo experiments from young adult mice, revealed that also cortical astrocytes in the living brain exibit GABAB receptor-mediated Ca(2+) elevations. At all astrocytic processes tested, local GABA or Baclofen brief applications induced long-lasting Ca(2+) oscillations, suggesting that all astrocytes have the potential to respond to GABA. Finally, in patch-clamp recordings it was found that Ca(2+) oscillations induced by Baclofen evoked astrocytic glutamate release and slow inward currents (SICs) in pyramidal cells from wild type but not IP3 R2(-/-) mice, in which astrocytic GABAB receptor-mediated Ca(2+) elevations are impaired. These data suggest that cortical astrocytes in the mouse brain can sense the activity of GABAergic interneurons and through their specific recruitment contribut to the distinct role played on the cortical network by the different subsets of GABAergic interneurons. PMID:26496414

  18. Long lasting effects of the conversion from natural forest to poplar plantation on soil microbial communities.

    PubMed

    Vitali, Francesco; Mastromei, Giorgio; Senatore, Giuliana; Caroppo, Cesarea; Casalone, Enrico

    2016-01-01

    In this study, we evaluate the long-lasting effects on soil microbial communities of a change within a single land-use category, specifically the conversion from natural forest to forest plantation. To minimize the effects of impacts other than land-use (i.e., climatic and anthropogenic), we chose three sites within a Natural Park, with homogeneous orographic and soil texture characteristics. We compared microbial diversity in a total of 156 soil samples from two natural mixed forests and a similar forest converted to poplar plantation about thirty years ago. The diversity and structure of bacterial and fungal communities were investigated by terminal restriction fragments length polymorphism (T-RFLP) analysis of the 16S-rRNA gene and the ITS-rDNA regions, respectively. Bacterial and fungal communities from the forest plantation, compared to those from natural forest soils, showed different community structure and lower α-diversity values, consistently with the significantly higher pH values and lower organic matter content of those soils. β-diversity values, the number of measured and estimated dominant OTUs, and their distribution among the three sites showed that microbial communities from the two natural forests were much more similar to each other than they were to communities from the poplar plantation, suggesting an effect of the forest conversion on the composition and diversity of soil microbial communities. α-diversity in cultivated forest soils had narrower temporal fluctuations than in natural forest soils, suggesting higher temporal stability of microbial communities. Overall, we demonstrated that the conversion from natural forest to forest plantation altered soil microbial communities, changing their structure, lowering their diversity, and causing a spatial and temporal homogenization. PMID:26686617

  19. Nonlinear Force-free Modeling of a Long-lasting Coronal Sigmoid

    NASA Astrophysics Data System (ADS)

    Savcheva, Antonia; van Ballegooijen, Adriaan

    2009-10-01

    A study of the magnetic configuration and evolution of a long-lasting quiescent coronal sigmoid is presented. The sigmoid was observed by Hinode/XRT and Transition Region and Coronal Explorer (TRACE) between 2007 February 6 and 12 when it finally erupted. We construct nonlinear force-free field models for several observations during this period, using the flux-rope insertion method. The high spatial and temporal resolution of the X-Ray Telescope (XRT) allows us to finely select best-fit models that match the observations. The modeling shows that a highly sheared field, consisting of a weakly twisted flux rope embedded in a potential field, very well describes the structure of the X-ray sigmoid. The flux rope reaches a stable equilibrium, but its axial flux is close to the stability limit of about 5 × 1020 Mx. The relative magnetic helicity increases with time from February 8 until just prior to the eruption on February 12. We study the spatial distribution of the torsion parameter α in the vicinity of the flux rope, and find that it has a hollow-core distribution, i.e., electric currents are concentrated in a current layer at the boundary between the flux rope and its surroundings. The current layer is located near the bald patch separatrix surface (BPSS) of the magnetic configuration, and the X-ray emission appears to come from this current layer/BPSS, consistent with the Titov and Démoulin model. We find that the twist angle Φ of the magnetic field increases with time to about 2π just prior to the eruption, but never reaches the value necessary for the kink instability.

  20. Wash resistance and residual efficacy of long-lasting polyester netting coated with alpha-cypermethrin (Interceptor) against malaria-transmitting mosquitoes in Assam, northeast India.

    PubMed

    Dev, V; Raghavendra, K; Singh, S P; Phookan, S; Khound, K; Dash, A P

    2010-04-01

    Malaria is endemic in Assam, northeast India, with low-to-moderate transmission of the causative parasites, mostly by Anopheles minimus. Plasmodium falciparum is the predominant parasite (>60%), with remaining cases being due to P. vivax. As an alternative intervention for malaria control, long-lasting insecticidal nets [Interceptor coated with alpha-cypermethrin 10% suspension concentrate (SC), 0.667% w/w, 0.2g/m(2)] underwent field evaluation for laboratory wash resistance and residual efficacy in field conditions against malaria-transmitting mosquitoes. Based on entomological observations, the Interceptor net intervention was the most effective, corresponding to the lowest mosquito vector density in experimental villages. There was virtual disappearance of A. minimus in Interceptor net villages in contrast to the untreated net intervention and the no-net control. Contact cone bioassay tests revealed 100% mortality in the A.minimus group of mosquito species in the community using the Interceptor net, which was consistent during the follow-up monitoring period (October 2006 to April 2007) in field conditions. Similar levels of mortality were observed in laboratory-washed nets compared with unwashed nets, and wash resistance was consistent even after the 20th serial wash at fortnightly intervals. Community compliance and acceptance of the Interceptor net was high, with decreased nuisance due to biting mosquitoes and other household insect pests being reported. PMID:19762058

  1. Evaluation of polyethylene-based long lasting treated bed net netprotect on anopheles mosquitoes, malaria incidence, and net longivity in Western kenya.

    PubMed

    Odhiambo, M T O; Skovmand, O; Vulule, J M; Kokwaro, E D

    2013-01-01

    We studied the effect on malaria incidence, mosquito abundance, net efficacy, net use rate, chemical analysis, and holes of a long lasting insecticide treated bed net (Netprotect) in western Kenya, 2007-2010. Nets were hung in 150 households 6 months before they were hung in a second, 2 km away. Indoor resting densities were monitored by pyrethrum spray catch and malaria cases by passive detection using clinical manifestations and rapid diagnostic test. The probability of finding An. arabiensis in the control area was 2.6 times higher than that in intervention area during the first 6 months. Human blood feeding index of Anopheles funestus declined 17%. After bed nets were hung in the second area, malaria incidence declined 25% down to the level in the first area. Incidence remained at this low level for 2 years. 90% of collected nets were efficacious after 3-year use. Deltamethrin dosage declined from 1.9 to 0.5 g/kg over 3 years. Attrition rate after 3 years was 21%. WHO hole index changed from 333 to 114 to 381 over the three years. This index summarizes the numbers of holes in size categories and multiplies with the mean hole area per category. It is very sensitive to the impact of big holes in a few nets. PMID:24194770

  2. Wash Resistance and Bioefficacy of Alpha-cypermethrin Long Lasting Impregnated Nets (LLIN-Interceptor®) against Anopheles stephensi using Tunnel Test

    PubMed Central

    Vatandoost, Hassan; Mamivandpoor, Hossein; Abai, Mohammad Reza; Shayeghi, Mansoreh; Rafi, Fatemeh; Raeisi, Ahmad; Nikpoor, Fatemeh

    2013-01-01

    Background: The Long-lasing insecticide impregnated nets (LLINs) is considered as an effective tools for malaria vector control. The aim of this study was to evaluate the residual efficacy of alpha-cypermethrin long lasting impregnated nets (LLIN-Interceptor®) against Anopheles stephensi using tunnel test. Methods: The wash-resistance of Interceptor® nets were assessed under laboratory conditions using tunnel test. Females of An. stephensi were released into the tunnel and then they were provided blood meals from guinea pigs. Bed nets were washed according to the standard procedure up to 20 times. The bioefficacy indicators such as inhibition of bloodmeal from experimental animal, knockdown, irritancy rate, survival rate, entry index and mortality were calculated. Results: It induced 90–100% mortalities in the population of An. stephensi up to 15 washes. The KT50 values reduced from 73.47 to 26.30 minutes in unwashed in comparison to one washed, respectively. The mean of mortality rate of blood-feeding inhibition and entry indexes was reached to 91.6%±2.8, 87.0±3.4 and 24.9±2.8 respectively after 20 washing. Conclusion: This net could provide a good personal protection against malaria vectors and could induce relatively high mortality, inhibit the blood-feeding as well as reduce the entry rates of female mosquitoes even after several washes. PMID:23785693

  3. Role of manganese in red long-lasting phosphorescence of manganese-doped diopside for in vivo imaging

    SciTech Connect

    Lecointre, A.; Bessière, A.; Priolkar, K.R.; Gourier, D.; Wallez, G.; Viana, B.

    2013-05-15

    Highlights: ► Long-lasting phosphorescence of CaMgSi{sub 2}O{sub 6}:Mn is studied for bioimaging application. ► CaMgSi{sub 2}O{sub 6}:Mn yields orange and red luminescence of Mn{sup II}{sub Ca} and Mn{sup II}{sub Mg}, respectively. ► Red Mn{sup II}{sub Mg} emission dominates long-lasting phosphorescence spectra. ► Mn mainly substitutes Mg. ► Mn{sup II}{sub Mg} plays the role of hole trap in the persistent luminescence mechanism. - Abstract: Materials with red long-lasting phosphorescence, such as Mn{sup II}-doped diopsides, can be used for small animal in vivo imaging. CaMgSi{sub 2}O{sub 6}:Mn powders with various amounts of Mn were prepared by sol–gel to investigate their long-lasting phosphorescence mechanism. X-ray diffraction, X-ray absorption fine and near-edge structure and electron paramagnetic resonance showed that manganese is quantitatively introduced in the structure as Mn{sup II}. Most of the Mn doping ions substitute Mg and possess a highly elongated octahedral environment. While photoluminescence and X-ray excited optical luminescence spectra show both orange (585 nm) and red (685 nm) {sup 4}T{sub 1} ({sup 4}G) → {sup 6}A{sub 1} ({sup 6}S) emission of Mn{sup II}{sub Ca} and Mn{sup II}{sub Mg}, respectively, Mn{sup II}{sub Mg} red emission dominates long-lasting phosphorescence and thermally stimulated luminescence spectra. These results point to Mn{sup II}{sub Mg} as the preferential hole trap and recombination center in the long-lasting phosphorescence mechanism. An intense persistent red emission suitable for in vivo imaging probes is obtained for the highest nominal Mn content (7.5%)

  4. 5-Fluorouracil-lipid conjugate: potential candidate for drug delivery through encapsulation in hydrophobic polyester-based nanoparticles.

    PubMed

    Ashwanikumar, N; Kumar, Nisha Asok; Nair, S Asha; Kumar, G S Vinod

    2014-11-01

    The encapsulation of 5-fluorouracil (5-FU) in hydrophobic polymeric materials is made feasible by a lipid-based prodrug approach. A lipid-5-FU conjugate of 5-FU with palmitic acid was synthesized in two-step process. A synthesized dipalmitoyl derivative (5-FUDIPAL) was characterized using Fourier transform infrared spectroscopy and (1)H-nuclear magnetic resonance. The 5-FUDIPAL was encapsulated in polyester-based polymers by the double emulsion-solvent evaporation method. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The thermal stability was assessed by differential scanning calorimetry data. In vitro release kinetics measurements of the drug from nanoparticles showed the controlled release pattern over a period of time. Cytotoxicity measurements by MTT assay confirmed that dipalmitoyl derivative in nano formulation successfully inhibited the cell growth. Thus the combined physical and biological evaluation of the different polyester-based nanoparticle containing the modified drug showed a facile approach to delivering 5-FU to the tumour site with enhanced efficacy. PMID:25110286

  5. Long-lasting transition toward sustainable elimination of desert malaria under irrigation development.

    PubMed

    Baeza, Andres; Bouma, Menno J; Dhiman, Ramesh C; Baskerville, Edward B; Ceccato, Pietro; Yadav, Rajpal Singh; Pascual, Mercedes

    2013-09-10

    In arid areas, people living in the proximity of irrigation infrastructure are potentially exposed to a higher risk of malaria due to changes in ecohydrological conditions that lead to increased vector abundance. However, irrigation provides a pathway to economic prosperity that over longer time scales is expected to counteract these negative effects. A better understanding of this transition between increased malaria risk and regional elimination, in particular whether it is slow or abrupt, is relevant to sustainable development and disease management. By relying on space as a surrogate for stages of time, we investigate this transition in a semidesert region of India where a megairrigation project is underway and expected to cover more than 1,900 million hectares and benefit around 1 million farmers. Based on spatio-temporal epidemiological cases of Plasmodium vivax malaria and land-use irrigation from remote sensing sources, we show that this transition is characterized by an enhanced risk in areas adjacent to the trunk of the irrigation network, despite a forceful and costly insecticide-based control. Moreover, this transition between climate-driven epidemics and sustained low risk has already lasted a decade. Given the magnitude of these projects, these results suggest that increased health costs have to be planned for over a long time horizon. They further highlight the need to integrate assessments of both health and environmental impacts to guide adaptive mitigation strategies. Our results should help to define and track these transitions in other arid parts of the world subjected to similar tradeoffs. PMID:23942131

  6. Systematic computational and experimental investigation of lithium-ion transport mechanisms in polyester-based polymer electrolytes

    SciTech Connect

    Webb, Michael A.; Jung, Yukyung; Pesko, Danielle M.; Savoie, Brett M.; Yamamoto, Umi; Coates, Geoffrey W.; Balsara, Nitash P.; Wang, Zhen -Gang; Miller, III, Thomas F.

    2015-07-10

    Understanding the mechanisms of lithium-ion transport in polymers is crucial for the design of polymer electrolytes. We combine modular synthesis, electrochemical characterization, and molecular simulation to investigate lithium-ion transport in a new family of polyester-based polymers and in poly(ethylene oxide) (PEO). Theoretical predictions of glass-transition temperatures and ionic conductivities in the polymers agree well with experimental measurements. Interestingly, both the experiments and simulations indicate that the ionic conductivity of PEO, relative to the polyesters, is far higher than would be expected from its relative glass-transition temperature. The simulations reveal that diffusion of the lithium cations in the polyesters proceeds via a different mechanism than in PEO, and analysis of the distribution of available cation solvation sites in the various polymers provides a novel and intuitive way to explain the experimentally observed ionic conductivities. This work provides a platform for the evaluation and prediction of ionic conductivities in polymer electrolyte materials.

  7. Long lasting paleolandscapes stability of the French Massif Central during the Mesozoic

    NASA Astrophysics Data System (ADS)

    Ricordel-Prognon, C.; Thiry, M.; Theveniaut, H.; Lagroix, F.

    2009-04-01

    , and more importantly no Jurassic cover was preserved (if such a cover was even deposited?) on the massif. Consequently, the Massif Central probably never did support an important (more than 500 m) sedimentary cover during the Mesozoic. These paleosurface ages provide important constraints to crustal dynamics modeling. Identification and dating of the successive continental unconformities are evidence for long lasting continental evolution and landscape stability of large areas of the Massif Central during the Mesozoic. The alternative hypothesis was that the Massif Central was subsidizing during Mesozoic time and covered with a 2,000 m thick sedimentary series, which was fairly quickly eroded during early Tertiary (Barbarand et al., 2001). In the future, making substantial progress in paleoweathering profiles dating, especially in the scope of improving time resolution, will allow attempting efficient correlation between the continental records and the diverse processes involved in their development (eustatism, climate, global and regional tectonics). Moreover, progress in dating paleoweathering features and continental azoic deposits, will allow to develop a "continental stratigraphy" of climatic and geomorphological events and to establish a mass balances between weathering/erosion weathering/erosion on land and deposition in basins. References Barbarand J., Lucazeau F., Pagel M., Séranne M., 2001, Burial and exhumation history of the south-eastern Massif Central (France) constrained by apatite fission track thermochronology. Tectonophysics, 335, 3-4, p. 275-290. Besse, J., Courtillot, V., 2003. Apparent true polar wander and the geometry of the geomagnetic field over the last 200 Myr: Correction: Journal of Geophysical Research, 108, p. 2300. Cogné, J.P., 2003. PaleoMac: a MacintoshTM application for treating paleomagnetic data and making plate reconstructions. Geochemistry Geophysics Geosystems, 4 (1), 1007. Edel J.B., Duringer P., 1997, The apparent polar

  8. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors.

    PubMed

    Campos, Alline Cristina; Ferreira, Frederico Rogério; Guimarães, Francisco Silveira

    2012-11-01

    Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD. Male Wistar rats exposed to a predator (cat) received, 1 h later, singled or repeated i.p. administration of vehicle or CBD. Seven days after the stress animals were submitted to the elevated plus maze. To investigate the involvement of 5HT1A receptors in CBD effects animals were pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore possible neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and BDNF protein expression were measured in the hippocampus, frontal cortex, amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure. Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator exposure 5HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder. PMID:22979992

  9. Durability assessment results suggest a serviceable life of two, rather than three, years for the current long-lasting insecticidal (mosquito) net (LLIN) intervention in Benin

    PubMed Central

    2014-01-01

    Background LLIN distribution, every three years, is a key intervention of Benin’s malaria control strategy. However, data from the field indicate that LLIN lifespan appears to vary based on both intrinsic (to the LLIN) and extrinsic factors. Methods We monitored two indicators of LLIN durability, survivorship and integrity, to validate the three-year-serviceable-life assumption. Interviews with net owners were used to identify factors associated with loss of integrity. Results Observed survivorship, after 18 months, was significantly less (p<0.0001) than predicted, based on the assumption that nets last three years. Instead, it was closer to predicted survivorship based on a two-year LLIN serviceable life assumption (p=0.03). Furthermore, the integrity of nearly one third of ‘surviving’ nets was so degraded that they were in need of replacement. Five factors: washing frequency, proximity to water for washing, location of kitchen, type of cooking fuel, and low net maintenance were associated with loss of fabric integrity. Conclusion A two-year serviceable life for the current LLIN intervention in Benin would be a more realistic program assumption. PMID:24507444

  10. Long-lasting D-region ionospheric modifications, caused by intense lightning in association with elve and sprite pairs

    NASA Astrophysics Data System (ADS)

    Haldoupis, Christos; Cohen, Morris; Cotts, Benjamin; Arnone, Enrico; Inan, Umran

    2012-08-01

    Observations show that intense +CG lightning discharges which trigger both an elve and a sprite are associated with long-lasting conductivity modifications in the upper D-region ionosphere. They are observed as strong perturbations in VLF signals propagating through the disturbed region, manifested as LOng Recovery Early VLF events (LORE), which can last up to 30 minutes. These same ionospheric modifications are also responsible for step-like changes, seen mostly in off-storm VLF transmissions, which offset signal levels even for longer times. The evidence suggests that when a very intense positive cloud to ground lightning stroke leads to an elve and a high altitude sprite, and possibly a sprite halo as well, there is production of long lasting elevations in electron density at VLF reflection heights that cause LOREs and severe effects on VLF propagation. The present results confirm past predictions and postulations that elves may be accompanied by long-lasting electron density perturbations in the lower ionosphere.

  11. Plasticity-associated gene Krox24/Zif268 is required for long-lasting behavioral effects of cocaine.

    PubMed

    Valjent, Emmanuel; Aubier, Benjamin; Corbillé, Anne-Gaëlle; Brami-Cherrier, Karen; Caboche, Jocelyne; Topilko, Piotr; Girault, Jean-Antoine; Hervé, Denis

    2006-05-01

    The extracellular signal-regulated kinases (ERKs) 1/2 pathway is stimulated by drugs of abuse in striatal neurons through coincident activation of dopamine D1 and glutamate NMDA receptors and is critical for long-lasting behavioral effects of these drugs. Although regulation of transcription is a major target of ERK, the precise mechanisms by which it contributes to behavioral alterations is not known. We examined the role of Zif268, an immediate-early gene induced by drugs of abuse under the control of ERK, in behavioral responses to cocaine using knock-in mutant mice in which Zif268 was replaced by LacZ. No biochemical or behavioral differences between mutant and wild-type mice were observed in basal conditions or in acute responses to cocaine injection. In contrast, locomotor sensitization to single or repeated cocaine injections was dramatically diminished in both heterozygous and homozygous Zif268 mutant mice. Conditioned place preference in response to cocaine was prevented in Zif268-deficient mice. This effect was not attributable to a general learning deficit because the mutant mice displayed normal conditioned place preference when food was used as reward. Our results provide direct genetic evidence for the requirement of Zif268 for long-lasting association of environmental context with specific behavioral responses after short exposures to cocaine. They also underline the common molecular machinery involved in long-lasting drug-induced behavioral alterations and the formation of other types of memory. PMID:16672671

  12. A Long Lasting β1 Adrenergic Receptor Stimulation of cAMP/Protein Kinase A (PKA) Signal in Cardiac Myocytes*

    PubMed Central

    Fu, Qin; Kim, Sungjin; Soto, Dagoberto; De Arcangelis, Vania; DiPilato, Lisa; Liu, Shubai; Xu, Bing; Shi, Qian; Zhang, Jin; Xiang, Yang K.

    2014-01-01

    Small-molecule, ligand-activated G protein-coupled receptors are generally thought to be rapidly desensitized within a period of minutes through receptor phosphorylation and internalization after repeated or prolonged stimulation. This transient G protein-coupled receptor activation remains at odds with many observed long-lasting cellular and physiological responses. Here, using live cell imaging of cAMP with a FRET-based biosensor and myocyte contraction assay, we show that the catecholamine-activated β1 adrenergic receptor (β1AR) continuously stimulates second messenger cAMP synthesis in primary cardiac myocytes and neurons, which lasts for more than 8 h (a decay t½ of 3.9 h) in cardiac myocytes. However, the β1AR-induced cAMP signal is counterbalanced and masked by the receptor-bound phosphodiesterase (PDE) 4D8-dependent cAMP hydrolysis. Inhibition of PDE4 activity recovers the receptor-induced cAMP signal and promotes contractile response in mouse hearts during extended periods of agonist stimulation. β1AR associates with PDE4D8 through the receptor C-terminal PDZ motif-dependent binding to synaptic-associated protein 97 (SAP97). Knockdown of SAP97 or mutation of the β1AR PDZ motif disrupts the complex and promotes sustained agonist-induced cAMP activity, PKA phosphorylation, and cardiac myocyte contraction response. Together, these findings unveil a long lasting adrenergic signal in neurons and myocytes under prolonged stimulation and an underappreciated role of PDE that is essential in classic receptor signaling desensitization and in maintaining a long lasting cAMP equilibrium for ligand-induced physiological response. PMID:24713698

  13. Serotonin 5-HT2 Receptors Induce a Long-Lasting Facilitation of Spinal Reflexes Independent of Ionotropic Receptor Activity

    PubMed Central

    Shay, Barbara L.; Sawchuk, Michael; Machacek, David W.; Hochman, Shawn

    2009-01-01

    Dorsal root-evoked stimulation of sensory afferents in the hemisected in vitro rat spinal cord produces reflex output, recorded on the ventral roots. Transient spinal 5-HT2C receptor activation induces a long-lasting facilitation of these reflexes (LLFR) by largely unknown mechanisms. Two Sprague-Dawley substrains were used to characterize network properties involved in this serotonin (5-HT) receptor-mediated reflex plasticity. Serotonin more easily produced LLFR in one substrain and a long-lasting depression of reflexes (LLDR) in the other. Interestingly, LLFR and LLDR were bidirectionally interconvertible using 5-HT2A/2C and 5-HT1A receptor agonists, respectively, regardless of substrain. LLFR was predominantly Aβ afferent fiber mediated, consistent with prominent 5-HT2C receptor expression in the Aβ fiber projection territories (deeper spinal laminae). Reflex facilitation involved an unmasking of polysynaptic pathways and an increased receptive field size. LLFR emerged even when reflexes were evoked three to five times/h, indicating an activity independent induction. Both the NMDA and AMPA/kainate receptor-mediated components of the reflex could be facilitated, and facilitation was dependent on 5-HT receptor activation alone, not on coincident reflex activation in the presence of 5-HT. Selective blockade of GABAA and/or glycine receptors also did not prevent reflex amplification and so are not required for LLFR. Indeed, a more robust response was seen after blockade of spinal inhibition, indicating that inhibitory processes serve to limit reflex amplification. Overall we demonstrate that the serotonergic system has the capacity to induce long-lasting bidirectional changes in reflex strength in a manner that is nonassociative and independent of evoked activity or activation of ionotropic excitatory and inhibitory receptors. PMID:16033939

  14. Nozzles of insecticide sprayers

    PubMed Central

    Knipe, Fred W.

    1955-01-01

    Certain performance characteristics of the insecticide-sprayer nozzle tip and its relationship to the pressure regulator are discussed. After analysing the effectiveness of residual spraying at various pressures, the author concludes that low-pressure application would best attain the pattern and rate of insecticide discharge laid down by the WHO Expert Committee on Insecticides. PMID:14364190

  15. Tennessee and Florida: Continuity and Change in Long-Lasting State Performance Funding Systems for Higher Education. CCRC Brief. Number 43

    ERIC Educational Resources Information Center

    Dougherty, Kevin J.; Natow, Rebecca S.

    2010-01-01

    This study analyzes changes over time in long-lasting state performance funding systems for higher education. It addresses two research questions: First, in what ways have long-lasting systems changed over time in funding levels, indicators used to allocate funds, and measures used for those indicators? Second, what political actors, actions, and…

  16. Long lasting MDM2/Translocator protein modulator: a new strategy for irreversible apoptosis of human glioblastoma cells

    PubMed Central

    Zappelli, Elisa; Marinelli, Luciana; Novellino, Ettore; Da Settimo, Federico; Taliani, Sabrina; Trincavelli, Maria L.; Martini, Claudia

    2016-01-01

    The development of multi-target drugs and irreversible modulators of deregulated signalling proteins is the major challenge for improving glioblastoma multiforme (GBM) treatment. Reversible single-target drugs are not sufficient to sustain a therapeutic effect over time and may favour the activation of alternative signalling pathways and the onset of resistance phenomena. Thus, a multi-target compound that has a long-lasting mechanism of action might have a greater and longer life span of anti-proliferative activity. Recently, a dual-target indol-3ylglyoxyldipeptide derivative, designed to bind to the Translocator Protein (TSPO) and reactivate p53 function via dissociation from its physiological inhibitor, murine double minute 2 (MDM2), has been developed as a potent GBM pro-apoptotic agent. In this study, this derivative was chemically modified to irreversibly bind MDM2 and TSPO. The new compound elicited a TSPO-mediated mitochondrial membrane dissipation and restored p53 activity, triggering a long-lasting apoptosis of GBM cells. These effects were sustained over time, involved a stable activation of extracellular signal regulated kinases and were specifically observed in cancer cells, in which these protein kinases are deregulated. Dual-targeting and irreversible binding properties combined in the same molecule may represent a useful strategy to overcome the time-limited effects elicited by classical chemotherapies. PMID:26761214

  17. Long-lasting deficits in hedonic and nucleus accumbens reactivity to sweet rewards by sugar overconsumption during adolescence.

    PubMed

    Naneix, Fabien; Darlot, Florence; Coutureau, Etienne; Cador, Martine

    2016-03-01

    Adolescence is a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system might constitute an important factor in vulnerability to pathological development. In spite of the dramatic increase in the consumption of sweet palatable foods during adolescence in our modern societies, the long-term consequences of such exposure on brain reward processing remain poorly understood. Here, we investigated in rats the long-lasting effects of sugar overconsumption during their adolescence on their adult reactivity to the hedonic properties of sweet rewards. Adolescent rats with continuous access to 5% sucrose solution (from postnatal day 30-46) showed escalating intake. At adulthood (post-natal day 70), using two-bottle free choice tests, sucrose-exposed rats showed lower intake than non-exposed rats suggesting decreased sensitivity to the rewarding properties of sucrose. In Experiment 1, we tested their hedonic-related orofacial reactions to intraoral infusion of tasty solutions. We showed that sucrose-exposed rats presented less hedonic reactions in response to sweet tastes leaving the reactivity to water or quinine unaltered. Hence, in Experiment 2, we observed that this hedonic deficit is associated with lower c-Fos expression levels in the nucleus accumbens, a brain region known to play a central role in hedonic processing. These findings demonstrate that a history of high sucrose intake during the critical period of adolescence induces long-lasting deficits in hedonic treatment that may contribute to reward-related disorders. PMID:26762310

  18. Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract.

    PubMed

    Dai, Jin; Zhang, Tianyuan; Wang, Luying; Shao, Lili; Zhu, Cuiming; Zhang, Yuyang; Failor, Courtney; Schenken, Robert; Baseman, Joel; He, Cheng; Zhong, Guangming

    2016-08-01

    Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarum can spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarum strain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivo imaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of the C. muridarum organisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridarum inoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract. PMID:27271744

  19. An inhibitor of neuronal exocytosis (DD04107) displays long-lasting in vivo activity against chronic inflammatory and neuropathic pain.

    PubMed

    Ponsati, Berta; Carreño, Cristina; Curto-Reyes, Verdad; Valenzuela, Belen; Duart, María José; Van den Nest, Wim; Cauli, Omar; Beltran, Beatriz; Fernandez, Jimena; Borsini, Franco; Caprioli, Antonio; Di Serio, Stefano; Veretchy, Mario; Baamonde, Ana; Menendez, Luis; Barros, Francisco; de la Pena, Pilar; Borges, Ricardo; Felipo, Vicente; Planells-Cases, Rosa; Ferrer-Montiel, Antonio

    2012-06-01

    Small peptides patterned after the N terminus of the synaptosomal protein of 25 kDa, a member of the protein complex implicated in Ca(2+)-dependent neuronal exocytosis, inhibit in vitro the release of neuromodulators involved in pain signaling, suggesting an in vivo analgesic activity. Here, we report that compound DD04107 (palmitoyl-EEMQRR-NH(2)), a 6-mer palmitoylated peptide that blocks the inflammatory recruitment of ion channels to the plasma membrane of nociceptors and the release of calcitonin gene-related peptide from primary sensory neurons, displays potent and long-lasting in vivo antihyperalgesia and antiallodynia in chronic models of inflammatory and neuropathic pain, such as the complete Freund's adjuvant, osteosarcoma, chemotherapy, and diabetic neuropathic models. Subcutaneous administration of the peptide produced a dose-dependent antihyperalgesic and antiallodynic activity that lasted ≥24 h. The compound showed a systemic distribution, characterized by a bicompartmental pharmacokinetic profile. Safety pharmacology studies indicated that the peptide is largely devoid of side effects and substantiated that the in vivo activity is not caused by locomotor impairment. Therefore, DD04107 is a potent and long-lasting antinociceptive compound that displays a safe pharmacological profile. These findings support the notion that neuronal exocytosis of receptors and neuronal algogens pivotally contribute to chronic inflammatory and neuropathic pain and imply a central role of peptidergic nociceptor sensitization to the pathogenesis of pain. PMID:22393248

  20. Radio observations of GRB 100418a: Test of an energy injection model explaining long-lasting GRB afterglows

    SciTech Connect

    Moin, A.; Wang, Z.; Chandra, P.; Miller-Jones, J. C. A.; Tingay, S. J.; Reynolds, C.; Taylor, G. B.; Frail, D. A.; Phillips, C. J.

    2013-12-20

    We present the results of our radio observational campaign of gamma-ray burst (GRB) 100418a, for which we used the Australia Telescope Compact Array, the Very Large Array, and the Very Long Baseline Array. GRB 100418a was a peculiar GRB with unusual X-ray and optical afterglow profiles featuring a plateau phase with a very shallow rise. This observed plateau phase was believed to be due to a continued energy injection mechanism that powered the forward shock, giving rise to an unusual and long-lasting afterglow. The radio afterglow of GRB 100418a was detectable several weeks after the prompt emission. We conducted long-term monitoring observations of the afterglow and attempted to test the energy injection model advocating that the continuous energy injection is due to shells of material moving at a wide range of Lorentz factors. We obtained an upper limit of γ < 7 for the expansion rate of the GRB 100418a radio afterglow, indicating that the range-of-Lorentz factor model could only be applicable for relatively slow-moving ejecta. A preferred explanation could be that continued activity of the central engine may have powered the long-lasting afterglow.

  1. Simultaneous and long-lasting hydrophilization of inner and outer wall surfaces of polytetrafluoroethylene tubes by transferring atmospheric pressure plasmas

    NASA Astrophysics Data System (ADS)

    Chen, Faze; Song, Jinlong; Huang, Shuai; Xu, Sihao; Xia, Guangqing; Yang, Dezheng; Xu, Wenji; Sun, Jing; Liu, Xin

    2016-09-01

    Plasma hydrophilization is a general method to increase the surface free energy of materials. However, only a few works about plasma modification focus on the hydrophilization of tube inner and outer walls. In this paper, we realize simultaneous and long-lasting plasma hydrophilization on the inner and outer walls of polytetrafluoroethylene (PTFE) tubes by atmospheric pressure plasmas (APPs). Specifically, an Ar atmospheric pressure plasma jet (APPJ) is used to modify the PTFE tube’s outer wall and meanwhile to induce transferred He APP inside the PTFE tube to modify its inner wall surface. The optical emission spectrum (OES) shows that the plasmas contain many chemically active species, which are known as enablers for various applications. Water contact angle (WCA) measurements, x-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) are used to characterize the plasma hydrophilization. Results demonstrate that the wettability of the tube walls are well improved due to the replacement of the surface fluorine by oxygen and the change of surface roughness. The obtained hydrophilicity decreases slowly during more than 180 d aging, indicating a long-lasting hydrophilization. The results presented here clearly demonstrate the great potential of transferring APPs for surface modification of the tube’s inner and outer walls simultaneously.

  2. Systematic computational and experimental investigation of lithium-ion transport mechanisms in polyester-based polymer electrolytes

    DOE PAGESBeta

    Webb, Michael A.; Jung, Yukyung; Pesko, Danielle M.; Savoie, Brett M.; Yamamoto, Umi; Coates, Geoffrey W.; Balsara, Nitash P.; Wang, Zhen -Gang; Miller, III, Thomas F.

    2015-07-10

    Understanding the mechanisms of lithium-ion transport in polymers is crucial for the design of polymer electrolytes. We combine modular synthesis, electrochemical characterization, and molecular simulation to investigate lithium-ion transport in a new family of polyester-based polymers and in poly(ethylene oxide) (PEO). Theoretical predictions of glass-transition temperatures and ionic conductivities in the polymers agree well with experimental measurements. Interestingly, both the experiments and simulations indicate that the ionic conductivity of PEO, relative to the polyesters, is far higher than would be expected from its relative glass-transition temperature. The simulations reveal that diffusion of the lithium cations in the polyesters proceeds viamore » a different mechanism than in PEO, and analysis of the distribution of available cation solvation sites in the various polymers provides a novel and intuitive way to explain the experimentally observed ionic conductivities. This work provides a platform for the evaluation and prediction of ionic conductivities in polymer electrolyte materials.« less

  3. Systematic Computational and Experimental Investigation of Lithium-Ion Transport Mechanisms in Polyester-Based Polymer Electrolytes

    PubMed Central

    2015-01-01

    Understanding the mechanisms of lithium-ion transport in polymers is crucial for the design of polymer electrolytes. We combine modular synthesis, electrochemical characterization, and molecular simulation to investigate lithium-ion transport in a new family of polyester-based polymers and in poly(ethylene oxide) (PEO). Theoretical predictions of glass-transition temperatures and ionic conductivities in the polymers agree well with experimental measurements. Interestingly, both the experiments and simulations indicate that the ionic conductivity of PEO, relative to the polyesters, is far higher than would be expected from its relative glass-transition temperature. The simulations reveal that diffusion of the lithium cations in the polyesters proceeds via a different mechanism than in PEO, and analysis of the distribution of available cation solvation sites in the various polymers provides a novel and intuitive way to explain the experimentally observed ionic conductivities. This work provides a platform for the evaluation and prediction of ionic conductivities in polymer electrolyte materials. PMID:27162971

  4. At Long Last

    ERIC Educational Resources Information Center

    Cooper, Kenneth J.

    2012-01-01

    Since 1980, Tufts has offered a minor called Africa in the New World, but for reasons lost to time, the private university north of Boston did not join other schools in the 1960s and 1970s in creating a major in what was usually called Black studies. A faculty-student committee's recommendation in 1972 to do so went unimplemented. African-American…

  5. Insecticide solvents: interference with insecticidal action.

    PubMed

    Brattsten, L B; Wilkinson, C F

    1977-06-10

    Several commercial solvent mixtures commonly used as insecticide carriers in spray formulations increase by more than threefold the microsomal N-demethylation of p-chloro N-methylaniline in midgut preparations of southern army-worm (Spodoptera eridania) larvae exposed orally to the test solvents. Under laboratory conditions, the same solvent mixtures exhibit a protective action against the in vivo toxicity of the insecticide carbaryl to the larvae. The data are discussed with respect to possible solvent-insecticide interactions occurring under field conditions and, more broadly, to potential toxicological hazards of these solvents to humans. PMID:860135

  6. Luminescence properties of a new bluish green long-lasting phosphorescence phosphor Ca9Bi(PO4)7:Eu2+,Dy3+

    NASA Astrophysics Data System (ADS)

    Jia, Yonglei; Li, Haifeng; Zhao, Ran; Sun, Wenzhi; Su, Qiang; Pang, Ran; Li, Chengyu

    2014-09-01

    A new long-lasting phosphorescence phosphor Ca9Bi(PO4)7:Eu2+,Dy3+ was synthesized by solid state reaction and its long-lasting phosphorescence properties were investigated for the first time. The X-ray powder diffraction, photoluminescence, long-lasting phosphorescence spectra, decay curves and thermoluminescence curves were measured. The Ca9Bi(PO4)7:Eu2+,Dy3+ phosphor exhibits an asymmetric emission centered at 475 nm, which can be ascribed to the 4f65d1-4f7 electronic transition of Eu2+. For the optimized sample, the bright bluish green long-lasting phosphorescence could be observed for 5 h by naked eyes after the excitation source was removed. The long-lasting phosphorescence spectra show that the co-doping of Dy3+ ions greatly enhance the intensity of the long-lasting phosphorescence. Meanwhile, the long-lasting phosphorescence mechanism of this phosphor was discussed. Based on our study, Dy3+ ions are suggested to increase the density of electron or hole traps so as to improve the performance of the bluish green phosphorescence of Eu2+, including the intensity and persistent time.

  7. Functional magnetic resonance connectivity studies in infants born preterm: suggestions of proximate and long-lasting changes in language organization.

    PubMed

    Kwon, Soo Hyun; Scheinost, Dustin; Vohr, Betty; Lacadie, Cheryl; Schneider, Karen; Dai, Feng; Sze, Gordon; Constable, R Todd; Ment, Laura R

    2016-03-01

    Sophisticated neuroimaging strategies demonstrate alterations in functional connectivity at school age, adolescence, and young adulthood in individuals born preterm. Recent data suggest these alterations are present in the postnatal period prior to term-equivalent age in neonates born preterm. Likewise, functional organization increases across development, but the influence of preterm birth on this fundamental infrastructure is immediate and unchanging. This article briefly reviews the current methods of measuring functional connectivity throughout development in those born preterm, and the association of functional connectivity with language disorders. Taken together, these data suggest that the effects of preterm birth on the functional organization of language in the developing brain are both proximate and long-lasting. PMID:27027605

  8. Long-lasting seizure-related anxiety in patients with temporal lobe epilepsy and comorbid psychiatric disorders.

    PubMed

    Boulogne, Sebastien; Catenoix, Hélène; Ryvlin, Philippe; Rheims, Sylvain

    2015-09-01

    Ictal anxiety is a frequent epileptic symptom; it is usually brief, associated with objective clinical signs, and is not positively influenced by external factors, in contrast to psychiatric disorders. These criteria can, however, be misleading, especially in patients with psychiatric comorbidities. We report two patients with a history of drug-resistant right temporal lobe epilepsy, who developed long-lasting psychiatric symptoms, suggestive of exacerbation of their comorbid anxiety disorder. However, intracranial EEG data and [(18)F] FDG-PET suggested that these symptoms were related to seizure activity, highlighting the difficulties in differentiating ictal symptoms from psychiatric episodes in some patients with epilepsy and comorbid psychiatric disorders. [Published with video sequence]. PMID:26235301

  9. Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission

    PubMed Central

    Chauvin, Alain; Moreau, Emmanuelle; Bonnet, Sarah; Plantard, Olivier; Malandrin, Laurence

    2009-01-01

    Babesia, the causal agent of babesiosis, are tick-borne apicomplexan protozoa. True babesiae (Babesia genus sensu stricto) are biologically characterized by direct development in erythrocytes and by transovarial transmission in the tick. A large number of true Babesia species have been described in various vertebrate and tick hosts. This review presents the genus then discusses specific adaptations of Babesia spp. to their hosts to achieve efficient transmission. The main adaptations lead to long-lasting interactions which result in the induction of two reservoirs: in the vertebrate host during low long-term parasitemia and throughout the life cycle of the tick host as a result of transovarial and transstadial transmission. The molecular bases of these adaptations in vertebrate hosts are partially known but few of the tick-host interaction mechanisms have been elucidated. PMID:19379662

  10. A comparison study between two long-lasting synoptic-scale wave trains and associated tropical cyclogeneses

    NASA Astrophysics Data System (ADS)

    Feng, Tao; Huang, Ronghui; Yang, Xiuqun; Wu, Liang; Zhou, Wen

    2016-04-01

    Tropical cyclogenesis is closely related to the activity of convectively coupled equatorial waves over the western North Pacific. Previous studies usually focused on the role of single cyclonic disturbance on tropical cyclogenesis. From a view of continuously propagating wave train, this study compared two long-lasting synoptic-scale wave trains with distinct tropical cyclone activities in 2004 and 2006 for investigating the essential factors affecting low-level perturbations and tropical cyclone activities. By employing CFSR reanalysis data, JTWC best track, TRMM precipitation rate and ERSST sea surface temperature, analyses show that the long-lasting wave train during 2004 mainly occurs over the region from 130°E to 160°E, featuring enhanced synoptic perturbations in association with enhanced tropical cyclone activity. In contrast, during 2006, the wave train maintains over the region from 120°E to 150°E with more poleward propagation, and the tropical cyclone activity is relatively inactive. Furthermore, the substantial differences between these two wave trains are that the primary propagation occurring at mid-lower-troposphere with a nearly equivalent barotropic structure during 2004, but at upper- and lower- troposphere with significant westward tilt during 2006. This is essentially attributed to effects of different vertical wind shears. In 2004, affected by weak easterly shear, the synoptic-scale waves are confined at mid-low-level. However, in 2006, waves are usually trapped at upper-troposphere by weak westerly shear. Thus, different patterns of vertical wind shears fundamentally affect the structures of synoptic-scale waves and associated tropical cyclogeneses.

  11. The physical and chemical characteristics of long-lasting trans-boundary mixed pollutants over East Asia

    NASA Astrophysics Data System (ADS)

    Hara, Y.; Uno, I.; Kobayashi, H.; Itahashi, S.; PAN, X.; Nishizawa, T.; Shimizu, A.; Matsui, I.; Sugimoto, N.

    2014-12-01

    Trans-boundary air pollution lasted about 1 week over East Asia from late May to early June 2014. Daily averaged PM2.5 and PM10 exceeded respectively 35μg/m3 and 100μg/m3 during this episode at Fukuoka, southeastern city of Japan. The continuous aerosol plumes were constructed by Asian dust and anthropogenic pollutants, and observed by many aerosol measurements, such as ground-based lidar, space-born lidar, Aerosol Chemical Speciation Analyzer (ACSA) and Polarization Optical Particle Counter (POPC). Regional chemical transport model was used to clarify the meteorological condition forming long-lasting aerosol plumes and the 3D structure. The continuous aerosol plume was made by 2 sequential low pressure systems passing over desert area, and subsequently generated blocking high pressure system over Japan. The averaged aerosol depolarization ratio derived by ground-based lidar and POPC at around 0.5μm during this episode were 0.11 and 0.146, these values were very low for dust case. ACSA data at Fukuoka also showed that coarse model nitrate and fine mode sulfate concentration was very high (3~6μg/m3 for coarse mode nitrate, 5-15 μg/m3 for fine mode sulfate) during this episode. These results suggested that transport of anthropogenic aerosols were occurred during this event together with dust plume. Coarse mode nitrate might be made by internal mixing between dust particles and nitrate. Numerical chemical transport model could not reproduced high concentration of coarse mode nitrate because model did not consider the process of internal mixing between dust particles and nitrate. Further vertical structure and mixing state during long-lasting trans-boundary pollution are clarified.

  12. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain

    PubMed Central

    WEISSHAUPT, ANGELA; WEDEKIND, FRANZISKA; KROLL, TINA; MCCARLEY, ROBERT W.

    2015-01-01

    SUMMARY Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day–1 for 5 consecutive days (SR1–SR5), followed by 3 unrestricted recovery sleep days (R1–R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26–31% from SR1 to R1). A decrease in b-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. PMID:25900125

  13. Reductions in frontocortical cytokine levels are associated with long-lasting alterations in reward valuation after methamphetamine.

    PubMed

    Stolyarova, Alexandra; Thompson, Andrew B; Barrientos, Ruth M; Izquierdo, Alicia

    2015-04-01

    Alterations in reward valuation are thought to have a central role at all stages of the addiction process. We previously reported work aversion in an effortful T-maze task following a binge exposure to methamphetamine, and no such changes in effort following escalating doses. Limitations of the T-maze task include its two available options, with an effort requirement, in the form of increasing barrier height, varying incrementally as a function of time, and reward magnitudes held constant. Reward preferences and choices, however, are likely affected by the number of options available and the manner in which alternatives are presented. In the present experiment, we investigated the long-lasting, off-drug effects of methamphetamine on reward choices in a novel effortful maze task with three possible courses of action, each associated with different effort requirements and reward magnitudes. Neuroinflammatory responses associated with drug exposure, proposed as one of the mechanisms contributing to suboptimal choices on effort-based tasks, were also examined. We investigated region-specific changes in pro- and anti-inflammatory markers in the mesocorticolimbic pathway after methamphetamine, and their relationship with animals' reward choices. We observed long-lasting, increased sensitivity to differences in reward magnitude in the methamphetamine group: animals were more likely to overcome greater effort costs to obtain larger rewards on our novel effortful maze task. These behavioral changes were strongly predicted by pronounced decreases in frontocortical cytokines, but not amygdalar or striatal markers. The present results provide the first evidence that neuroinflammatory processes are associated with alterations in reward valuation during protracted drug withdrawal. PMID:25409594

  14. Long-lasting genomic instability following arsenite exposure in mammalian cells: the role of reactive oxygen species.

    PubMed

    Sciandrello, G; Mauro, M; Catanzaro, I; Saverini, M; Caradonna, F; Barbata, G

    2011-08-01

    Previously, we reported that the progeny of mammalian cells, which has been exposed to sodium arsenite for two cell cycles, exhibited chromosomal instability and concurrent DNA hypomethylation, when they were subsequently investigated after two months of subculturing (about 120 cell generations) in arsenite-free medium. In this work, we continued our investigations of the long-lasting arsenite-induced genomic instability by analyzing additional endpoints at several time points during the cell expanded growth. In addition to the progressive increase of aneuploid cells, we also noted micronucleated and multinucleated cells that continued to accumulate up to the 50th cell generation, as well as dicentric chromosomes and/or telomeric associations and other complex chromosome rearrangements that began to appear much later, at the 90th cell generation following arsenite exposure. The increasing genomic instability was further characterized by an increased frequency of spontaneous mutations. Furthermore, the long-lasting genomic instability was related to elevated levels of reactive oxygen species (ROS), which at the 50th cell generation appeared higher than in stable parental cells. To gain additional insight into the continuing genomic instability, we examined several individual clones isolated at different time points from the growing cell population. Chromosomally and morphologically unstable cell clones, the number of which increased with the expanded growth, were also present at early phases of growth without arsenite. All genomically unstable clones exhibited higher ROS levels than untreated cells suggesting that oxidative stress is an important factor for the progression of genomic instability induced by arsenite. PMID:21520292

  15. Long-lasting adverse effects after short-term low-dose treatment with metoclopramide for vomiting.

    PubMed

    Dahl, Eilif; Diskin, Arthur L

    2014-01-01

    Metoclopramide is commonly used to treat vomiting caused by seasickness and acute gastroenteritis on cruise ships and serious adverse effects have not been reported from use at sea. We report severe long-lasting adverse effects in a young female seafarer following short-term, low-dose use of metoclopramide. During rough seas a 25-year-old female musician on a cruise vessel presented with nausea and vomiting. She was given intramuscular metoclopramide 10 mg and diphenhydramine 25 mg. Vomiting stopped after the injections, but she felt tired, confused and dizzy. She then had been taking metoclopramide 5-10 mg a day, but stopped after a total per oral dose of 30 mg as she developed disturbing symptoms that she related to the medication, including dizziness, anxiety, fatigue, depression and involuntary movements (twitches, jerks, ticks, and tremors of the eyelids, tongue, neck, fingers, arms and legs). Neurological examination, blood tests, electrocardiography and magnetic resonance imaging of the brain were all normal. Although gradually reduced in strength and frequency, the adverse effects were very disturbing for about 10 months, but at 13 months she was almost fully recovered. For many years numerous vomiting sea travellers have been successfully treated with a single parenteral 10 mg dose of metoclopramide. There are no obvious reasons why our previously healthy patient experienced such serious and long-lasting side effects after low-dose, short-term metoclopramide administration. Until more is known, metoclopramide should be reserved for debilitating cases - and only be given after other remedies have been tried and found ineffective. PMID:24677122

  16. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons

    PubMed Central

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-01-01

    The CB1 cannabinoid receptor, the main target of Δ9-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling. PMID:26460022

  17. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

    PubMed

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-11-01

    The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling. PMID:26460022

  18. The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

    PubMed

    Montagud-Romero, Sandra; Daza-Losada, Manuel; Vidal-Infer, Antonio; Maldonado, Concepción; Aguilar, María A; Miñarro, Jose; Rodríguez-Arias, Marta

    2014-01-01

    The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype. PMID:24658541

  19. The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging.

    PubMed

    Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria

    2016-09-15

    Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. PMID:27185737

  20. The Novelty-Seeking Phenotype Modulates the Long-Lasting Effects of Intermittent Ethanol Administration during Adolescence

    PubMed Central

    Montagud-Romero, Sandra; Daza-Losada, Manuel; Vidal-Infer, Antonio; Maldonado, Concepción; Aguilar, María A.; Miñarro, Jose; Rodríguez-Arias, Marta

    2014-01-01

    The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels - measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype. PMID:24658541

  1. Novel 18F labeling strategy for polyester-based NPs for in vivo PET-CT imaging.

    PubMed

    Di Mauro, Primiano Pio; Gómez-Vallejo, Vanessa; Baz Maldonado, Zuriñe; Llop Roig, Jordi; Borrós, Salvador

    2015-03-18

    Drug-loaded nanocarriers and nanoparticulate systems used for drug release require a careful in vivo evaluation in terms of physicochemical and pharmacokinetic properties. Nuclear imaging techniques such as positron emission tomography (PET) are ideal and noninvasive tools to investigate the biodistribution and biological fate of the nanostructures, but the incorporation of a positron emitter is required. Here we describe a novel approach for the (18)F-radiolabeling of polyester-based nanoparticles. Our approach relies on the preparation of the radiolabeled active agent 4-[(18)F]fluorobenzyl-2-bromoacetamide ([(18)F]FBBA), which is subsequently coupled to block copolymers under mild conditions. The labeled block copolymers are ultimately incorporated as constituent elements of the NPs by using a modified nano coprecipitation method. This strategy has been applied in the current work to the preparation of peptide-functionalized NPs with potential applications in drug delivery. According to the measurements of particle size and zeta potential, the radiolabeling process did not result in a statistically significant alteration of the physicochemical properties of the NPs. Moreover, radiochemical stability studies showed no detachment of the radioactivity from NPs even at 12 h after preparation. The radiolabeled NPs enabled the in vivo quantification of the biodistribution data in rats using a combination of imaging techniques, namely, PET and computerized tomography (CT). Low accumulation of the nanoparticles in the liver and their elimination mainly via urine was found. The different biodistribution pattern obtained for the "free" radiolabeled polymer suggests chemical and radiochemical integrity of the NPs under investigation. The strategy reported here may be applied to any polymeric NPs containing polymers bearing a nucleophile, and hence our novel strategy may find application for the in vivo and noninvasive investigation of a wide range of NPs. PMID:25710619

  2. Pattern of nonadrenergic, noncholinergic responses during short- or long-lasting electrical stimulation in guinea-pig ileum.

    PubMed

    Ivancheva, C; Pencheva, N; Radomirov, R

    1997-08-01

    1. The pattern of responses of longitudinally oriented guinea pig ileum organ bath preparations was studied during short- (1-5 sec) or long-lasting (20 sec) electrical field stimulation (EFS, 0.8 msec, 40 V, 1-20 Hz). 2. In the presence of phentolamine (5 microM), propranolol (5 microM), and atropine (3 microM), the EFS elicited nonadrenergic, noncholinergic (NANC), tetrodotoxin (0.3 microM)-sensitive responses. 3. The 1-sec EFS evoked relaxation. The response to 5-sec EFS consisted of relaxation followed by twitch, whereas relaxation, twitch and tonic contraction characterized the NANC response to 20-sec EFS. The maximum relaxation was observed at 10-Hz short- or long-lasting EFS. 4. Both N-G-nitro-L-arginine (L-NNA, 0.1-0.5 mM) and apamin (1-5 microM) concentration dependently inhibited the relaxation of the NANC response to 10-Hz 20-sec EFS. During L-NNA treatment, the twitch and the tonic contractions were increased. The inhibitory effect of L-NNA was reversed by L-arginine (0.1-0.5 mM) but not by D-arginine. Sodium nitroprusside (1-10 microM) was without effect. 5. AP 13.2 ACOH (0.1 microM), a blocker of Substance P receptors, inhibited the twitch and the tonic contractions. The contractions were decreased after desensitization of purinoceptors by ATP and in the presence of the GABA(A) receptor antagonist bicuculline (30 microM). 6. Depending on the EFS duration, a subsequent occurrence of relaxation and contractions characterized the NANC responses. It seems that relaxation is mediated by nitric oxide whereas Substance P and ATP are involved in the maintenance of the twitch and the tonic contractions. Nitric oxide appears to exert an inhibitory effect on the excitatory transmitters, whereas purinergic mechanism(s) could modulate the nitric oxide-dependent relaxation. PMID:9251905

  3. Long-Lasting Cortical Reorganization as the Result of Motor Imagery of Throwing a Ball in a Virtual Tennis Court

    PubMed Central

    Cebolla, Ana M.; Petieau, Mathieu; Cevallos, Carlos; Leroy, Axelle; Dan, Bernard; Cheron, Guy

    2015-01-01

    In order to characterize the neural signature of a motor imagery (MI) task, the present study investigates for the first time the oscillation characteristics including both of the time-frequency measurements, event related spectral perturbation and intertrial coherence (ITC) underlying the variations in the temporal measurements (event related potentials, ERP) directly related to a MI task. We hypothesize that significant variations in both of the time-frequency measurements underlie the specific changes in the ERP directly related to MI. For the MI task, we chose a simple everyday task (throwing a tennis ball), that does not require any particular motor expertise, set within the controlled virtual reality scenario of a tennis court. When compared to the rest condition a consistent, long-lasting negative fronto-central ERP wave was accompanied by significant changes in both time frequency measurements suggesting long-lasting cortical activity reorganization. The ERP wave was characterized by two peaks at about 300 ms (N300) and 1000 ms (N1000). The N300 component was centrally localized on the scalp and was accompanied by significant phase consistency in the delta brain rhythms in the contralateral central scalp areas. The N1000 component spread wider centrally and was accompanied by a significant power decrease (or event related desynchronization) in low beta brain rhythms localized in fronto-precentral and parieto-occipital scalp areas and also by a significant power increase (or event related synchronization) in theta brain rhythms spreading fronto-centrally. During the transition from N300 to N1000, a contralateral alpha (mu) as well as post-central and parieto-theta rhythms occurred. The visual representation of movement formed in the minds of participants might underlie a top-down process from the fronto-central areas which is reflected by the amplitude changes observed in the fronto-central ERPs and by the significant phase synchrony in contralateral fronto

  4. The impact of insecticides management linked with resistance expression in Anopheles spp. populations.

    PubMed

    Silva, Guilherme Liberato da; Pereira, Thiago Nunes; Ferla, Noeli Juarez; Silva, Onilda Santos da

    2016-06-01

    The resistance of some species of Anopheles to chemical insecticides is spreading quickly throughout the world and has hindered the actions of prevention and control of malaria. The main mechanism responsible for resistance in these insects appears to be the target site known as knock-down resistance (kdr), which causes mutations in the sodium channel. Even so, many countries have made significant progress in the prevention of malaria, focusing largely on vector control through long-lasting insecticide nets (LLINs), indoor residual spraying and (IRS) of insecticides. The objective of this review is to contribute with information on the more applied insecticides for the control of the main vectors of malaria, its effects, and the different mechanisms of resistance. Currently it is necessary to look for others alternatives, e.g. biological control and products derived from plants and fungi, by using other organisms as a possible regulator of the populations of malaria vectors in critical outbreaks. PMID:27383351

  5. Longitudinal frequency variation of long-lasting EMIC Pc1-Pc2 waves localized in the inner magnetosphere

    NASA Astrophysics Data System (ADS)

    Kim, K.-H.; Shiokawa, K.; Mann, I. R.; Park, J.-S.; Kwon, H.-J.; Hyun, K.; Jin, H.; Connors, M.

    2016-02-01

    Long-lasting (> 20 h) electromagnetic ion cyclotron (EMIC) Pc1-Pc2 waves were observed by the Athabasca (L =˜ 4.6) induction magnetometer and Canadian Array for Realtime Investigations of Magnetic Activity (L =˜ 4-6) fluxgate magnetometers on 5 April 2007. These waves showed a systematic frequency change with local time, the minimum frequency near dusk, and the maximum frequency near dawn. Assuming the plasmapause as a potential source region of the waves, we estimated the plasmapause location from localized proton enhancement (LPE) events observed at NOAA-Polar Orbiting Environmental Satellites and METOP-2 satellites. We found that the longitudinal frequency variation of EMIC waves has a clear correlation with the estimated plasmapause location and that the waves are in the frequency band between the equatorial helium and oxygen gyrofrequencies at the estimated plasmapause. With our analysis results we suggest that the LPE events are caused by wave-particle interaction with the helium band EMIC waves generated near the plasmapause.

  6. Postnatal Exposure to Sodium Arsenite (NaAsO2) Induces Long Lasting Effects in Rat Testes

    PubMed Central

    Kaushal, Parul; Dhar, Pushpa; Shivaprasad, Somesh Meludurga; Mehra, Raj D.

    2012-01-01

    Objective: The present study was undertaken to investigate the effects of early postnatal exposure to sodium arsenite (NaAsO2) on rat testis. Materials and Methods: Wistar rat pups were administered aqueous solution of NaAsO2, 1.5 mg/kg body weight (bw) (experimental) and distilled water (control), respectively, by intraperitoneal route (i.p.) from postnatal day (PND) 1 to 14. Testes were collected after 1, 7 and 36 days (at PND 15, 21 and 50) after the treatment period (PND1-14) from the animals and immersion fixed in Bouin's fluid followed by paraffin embedding. Seven micrometer thick serial sections were cut and stained with hematoxylin and eosin for light microscopic observations. At PND 50, morphological features of sperms and their counting was carried out besides processing the perfusion-fixed testes for electron microscopy (EM). Results and Conclusions: The observations revealed an altered morphology of the seminiferous tubules (ST) along with degeneration and dissociation of spermatogenic cells in the experimental animals at PND 15, 21 and 50. Also, increased number of sperms with abnormal morphology and decreased sperm count was noted in the experimental animals. These features together with electron microscopic observations of abnormal mitochondria and apoptotic nuclei of spermatogonia and spermatocytes could be indicative of long-lasting adverse effects on the rat testis induced by exposure to As during early postnatal period. PMID:22778523

  7. Areas of long-lasting anthropopression: Assessment and monitoring of pollution potential to soil and ground water

    SciTech Connect

    Twardowska, I.

    1995-12-31

    Correct identification and assessment of the prevailing source, scope and extent of pollution potential is essential for providing efficient preventive remedial actions and management of already occurring contamination on the least-cost basis. In this paper, the identification/assessment procedure for the areas with several sources of long-lasting nonpoint contamination is illustrated by example of the Wroclaw waterworks area in Poland impacted by emission from ferro-chrome smelter and power plant, as well as by various sources of polycyclic aromatic hydrocarbons. Investigations and studies comprised (1) analysis of physicochemical composition of emitted particulates and deposited wastes their time-dependant transformations and leachability of contaminants as a function of time (2) direct multilevel sampling of dump and vadose zone profiles and examination of pore solutions and matrices; (3) ground-water survey in saturation zone; (4) investigation on infiltration and contaminant migration for radioisotope data; (5) survey of surface water quality; (6) numerical simulation and direct measurements of particulate emission from various sources; (7) analysis and comparison of data on point and nonpoint emission/imission of contaminants with the extent and scope of contamination. In another example, current investigations on the vadose zone screening and monitoring in the area of a high environmental risk in the vicinity of Sendzimir Steelworks near Cracow, Poland, are presented.

  8. Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses

    PubMed Central

    Low, Lucie A.; Bauer, Lucy C.; Pitcher, Mark H.; Bushnell, M. Catherine

    2016-01-01

    Abstract With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the “nociceptive” central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli. PMID:27058679

  9. Antioxidants have a rapid and long-lasting effect on neuritic abnormalities in APP:PS1 mice.

    PubMed

    Garcia-Alloza, Monica; Borrelli, Laura A; Hyman, Bradley T; Bacskai, Brian J

    2010-12-01

    Senile plaques are a major pathological hallmark of Alzheimer's disease (AD). Compelling evidence suggests that senile plaques lead to structural alterations of neuronal processes and that local toxicity may be mediated by increased oxidative stress. Anti-oxidant therapy can alleviate the neuronal abnormalities in APP mice, but the time-course of this beneficial effect is unknown. We used multiphoton microscopy to assess in vivo the characteristics of antioxidant treatment on senile plaques and neurites in AD model mice (APPswe/PS1dE9). We observed that α-phenyl-N-tert-butyl nitrone (PBN), Ginkgo biloba extract (EGb 761) and Trolox had no effect on the size of existing senile plaques. However, all anti-oxidants had a straightening effect on curved neurites. This effect was detected as soon as 4 days after commencing the treatment, and was maintained after 1 month of daily treatment, with no further increase in the effect. The straightening of neurites persisted 15 days after stopping the treatment. These data indicate that neuronal plasticity is fast and still active in adult animals, and suggest that amelioration of the neuritic distortions associated with senile plaques with antioxidants is both rapid and long lasting. PMID:19124175

  10. Discontinuation of alpha-interferon treatment in patients with chronic myeloid leukemia in long-lasting complete molecular response.

    PubMed

    Latagliata, Roberto; Romano, Angela; Mancini, Marco; Breccia, Massimo; Carmosino, Ida; Vozella, Federico; Montagna, Chiara; Volpicelli, Paola; De Angelis, Federico; Petrucci, Luigi; Serrao, Alessandra; Molica, Matteo; Salaroli, Adriano; Diverio, Daniela; Alimena, Giuliana

    2016-01-01

    To evaluate follow-up after α-interferon (IFN) discontinuation, 23 patients with chronic myeloid leukemia (CML) in stable complete molecular response (CMolR) with IFN were revisited. After a median IFN treatment of 105.8 months (IR 56.1 - 127.3), all patients discontinued IFN for prolonged CMolR (12), intolerance (8) or planned ABMT (3). After 12.5 months, one patient developed an extramedullar blast crisis. Four patients needed to start imatinib, all achieving again molecular response. Eighteen patients are still off-therapy (median time from IFN discontinuation 125.5 months, IR 86.9-205.3); among these, five are BCR-ABL negative, six present with a sporadic positivity (BCR-ABL ratio < 0.1) and seven show a stable and long-lasting mild positivity (BCR-ABL ratio < 0.5). Patients in prolonged CMolR with IFN have low risk of recurrence after discontinuation; the reappearance of a BCR-ABL positivity < 0.5 did not always precede a relapse, suggesting mechanisms of immunological control induced by IFN. PMID:25997497

  11. DNA Superresolution Structure of Reed-Sternberg Cells Differs Between Long-Lasting Remission Versus Relapsing Hodgkin's Lymphoma Patients.

    PubMed

    Righolt, Christiaan H; Knecht, Hans; Mai, Sabine

    2016-07-01

    Recent developments in microscopy have led to superresolution microscopy images of cells. Structured illumination microscopy was used before to reveal new details in the DNA structure and the structure of the DNA-free space in the DAPI-stained cell nuclei of the Hodgkin's lymphoma HDLM-2 cell line. This study extends this technology to primary pre-treatment classical Hodgkin's lymphoma samples of ten patients. Significant differences in both the DNA structure and the structure of the DNA-free space were detected between lymphocytes and malignant cells. Both types of structures were similar for lymphocytes of different patients. When the patients were un-blinded and grouped based on their clinical outcome, either non-relapsed or relapsed, a significant difference in the DNA structure of their Reed-Sternberg (RS) cells was found. Since, RS cells develop from mono-nucleated Hodgkin (H) cells, these data suggest distinct architectural restructuring of nuclei during RS cell formation in patients going to long-lasting remission versus relapse. J. Cell. Biochem. 117: 1633-1637, 2016. © 2015 Wiley Periodicals, Inc. PMID:26639515

  12. Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line.

    PubMed

    Zanette, Caterina; Pelin, Marco; Crosera, Matteo; Adami, Gianpiero; Bovenzi, Massimo; Larese, Francesca Filon; Florio, Chiara

    2011-08-01

    For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products designed to come in direct contact with the skin. In this study we investigated the effects of Ag NPs on skin using the human-derived keratinocyte HaCaT cell line model. Ag NPs caused a concentration- and time-dependent decrease of cell viability, with IC(50) values of 6.8 ± 1.3 μM (MTT assay) and 12 ± 1.2 μM (SRB assay) after 7 days of contact. A 24h treatment, followed by a 6 day recovery period in Ag NPs-free medium, reduced cell viability with almost the same potency (IC(50)s of 15.3 ± 4.6 and 35 ± 20 μM, MTT and SRB assays, respectively). Under these conditions, no evidence of induction of necrotic events (propidium iodide assay) was found. Apocynin, NADPH-oxidase inhibitor, or N(G)-monomethyl-L-argynine, nitric oxide synthase inhibitor, did not prevent NPs-induced reduction of cell viability. TEM analysis of cells exposed to NPs for 24h revealed alteration of nuclear morphology but only a marginal presence of individual NPs inside the cells. These results demonstrate that on HaCaT keratinocytes a relatively short time of contact with Ag NPs causes a long-lasting inhibition of cell growth, not associated with consistent Ag NPs internalization. PMID:21501681

  13. Initial breakdown and fast leaders in lightning discharges producing long-lasting disturbances of the lower ionosphere

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.; Zhu, Y.; Tran, M. D.; Rakov, V. A.; Pilkey, J. T.; Caicedo, J. A.; Hare, B.; Jordan, D. M.; Uman, M. A.

    2016-06-01

    The recent discovery of long recovery, early VLF scattering events (LOREs) indicates that the electric field changes from lightning discharges are capable of producing long-lasting disturbances (up to tens of minutes) in the upper mesosphere and lower ionosphere. Comparison of lightning mapping array, broadband (up to 10 MHz) electric field, and VLF (˜300 Hz to 42 kHz) magnetic field measurements shows that the field changes produced by initial breakdown (IB) processes and the following leaders in natural, cloud-to-ground lightning discharges are detectable in VLF magnetic field measurements at long distances. IB radiation has been detected in VLF for lightning discharges occurring up to 2630 km away from the VLF observing station. Radio atmospherics associated with 52 LOREs, 51 regular recovery events, and 3098 flashes detected by National Lightning Detection Network and/or GLD360 were examined for IB radiation occurring up to 15 ms before the return stroke. Our analysis reveals that in contrast to regular recovery early VLF events, LOREs are strongly associated with lightning discharges which exhibit an intense IB process and a fast first leader (typical duration <4 ms). These experimental results demonstrate that initial breakdown and leader processes are indicators of discharge properties highly relevant to the total energy transfer between lightning discharges and the middle/upper atmosphere.

  14. Long-lasting chemiluminescence of luminol on electrochemically pre-oxidized platinum electrodes in NaOH solution.

    PubMed

    Lin, X Q; Sun, Y G; Cui, H

    2000-01-01

    A long-lasting bright chemiluminescence (CL) of luminol was generated at polycrystalline platinum electrodes with open circuit. The CL can last for several hours with the presence of O(2) in the solution when the electrode was preoxidized at potentials more positive than 1.10 V vs. SCE. The effects of the varieties of solution conditions and surface states of the electrode on the CL intensity and the interfacial potential of the electrode were investigated. It was proposed that PtO was generated at the pre-oxidized potentials and played a role of catalyst of luminol oxidation for generating the CL. The redox couple of PtO/Pt(active) at the electrode surface was maintained in the presence of O(2) and luminol, and generated the interfacial potential more positive than 140 mV. Mathematical treatment of the reaction mechanism was conducted, which led to an approximated expression of a steady CL intensity (I(CL)) as a function of the pre-polarization potential (E( h)) and time (tau( h)) of the electrode. An empirical equation, (I(CL))(4/3) = 3480(-1 + 0.82E( h) + 0.037 ln tau( h)), was estimated from the experimental data. PMID:11038487

  15. Effective insect repellent formulation in both surfactantless and classical microemulsions with a long-lasting protection for human beings.

    PubMed

    Drapeau, Jeremy; Verdier, Marie; Touraud, Didier; Kröckel, Ulla; Geier, Martin; Rose, Andreas; Kunz, Werner

    2009-06-01

    The aim of this work is to develop a new generation of repellent products with a long-lasting protection based on a natural component, para-menthane-3,8-diol (PMD). The active is first rendered soluble in a surfactantless microemulsion (H(2)O/(i)PrOH/PMD) and then in classical microemulsions. The presence of self-associated nanostructures is detected by dynamic light scattering (DLS). A synergetic system of surfactants (Cremophor) RH40 and Texapon N70) is used. Additionally, 2-ethylhexane-1,3-diol and ethyl (-)-(S)-lactate are incorporated. The final product contains, as main components, 46% of H(2)O, 25% of (i)PrOH, 20% of non-H(2)O-soluble PMD, and only 4% of surfactants. Investigations of lasting protection on human volunteers are carried out using a cage test bioassay protocol and Aedes aegypti mosquitoes. A complete protection of 315 min is found on the test persons using the surfactantless microemulsion. An extension is observed with the final formulation to reach a mean of complete protection of 385 min. This study demonstrates that alternative formulations using a natural active instead of synthetic chemicals like N,N-diethyl-m-methylbenzamide (DEET) can be efficient for human protection against mosquitoes. PMID:19551736

  16. β3 Integrin Promotes Long-Lasting Activation and Polarization of Vascular Endothelial Growth Factor Receptor 2 by Immobilized Ligand

    PubMed Central

    Ravelli, Cosetta; Grillo, Elisabetta; Corsini, Michela; Coltrini, Daniela

    2015-01-01

    Objective— During neovessel formation, angiogenic growth factors associate with the extracellular matrix. These immobilized factors represent a persistent stimulus for the otherwise quiescent endothelial cells (ECs), driving directional EC migration and proliferation and leading to new blood vessel growth. Vascular endothelial growth factor receptor 2 (VEGFR2) is the main mediator of angiogenesis. Although VEGFR2 signaling has been deeply characterized, little is known about its subcellular localization during neovessel formation. Aim of this study was the characterization and molecular determinants of activated VEGFR2 localization in ECs during neovessel formation in response to matrix-immobilized ligand. Approach and Results— Here we demonstrate that ECs stimulated by extracellular matrix–associated gremlin, a noncanonical VEGFR2 ligand, are polarized and relocate the receptor in close contact with the angiogenic factor–enriched matrix both in vitro and in vivo. GM1 (monosialotetrahexosylganglioside)-positive planar lipid rafts, β3 integrin receptors, and the intracellular signaling transducers focal adhesion kinase and RhoA (Ras homolog gene family, member A) cooperate to promote VEGFR2 long-term polarization and activation. Conclusions— A ligand anchored to the extracellular matrix induces VEGFR2 polarization in ECs. Long-lasting VEGFR2 relocation is closely dependent on lipid raft integrity and activation of β3 integrin pathway. The study of the endothelial responses to immobilized growth factors may offer insights into the angiogenic process in physiological and pathological conditions, including cancer, and for a better engineering of synthetic tissue scaffolds to blend with the host vasculature. PMID:26293466

  17. Clinical factors increasing radiation doses to patients undergoing long-lasting procedures: Abdominal stent-graft implantation

    PubMed Central

    Majewska, Natalia; Stanisic, Michal G.; Blaszak, Magdalena Aleksandra; Juszkat, Robert; Frankiewicz, Maciej; Krasinski, Zbigniew; Makalowski, Marcin; Majewski, Waclaw

    2011-01-01

    Summary Background An important negative factor of EVAR is the radiation acquired during long-lasting procedures. The aim of the study was to document the radiation doses of EVAR and to discuss potential reasons for prolongation of radiological procedures. Material/Methods Dose-area product (DAP) (Gy cm2) and air kerma (AK) (Gy) obtained during EVAR from 92 patients were analyzed retrospectively in regards to body mass index (BMI), angulations of aneurysm neck, length of aneurysm neck and occurrence of tortuosity of iliac arteries. Results Total AK for fluoroscopy differed significantly between normal BMI (373 mGy) and BMI 25–29.9 (1125 mGy) or BMI >30 (1085 mGy). Iliac artery tortuosities >45° and short aneurysm necks caused higher doses of total AK (1097 mGy and 1228 mGy, respectively) than iliac artery tortuosities <45° and long aneurysm necks (605 mGy and 720 mGy, respectively). Conclusions The main factors contributing to a high radiation dose being acquired by patients during EVAR are: BMI >25, tortuosity of iliac arteries >45° and short aneurysm necks. PMID:22037751

  18. TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria.

    PubMed

    Alba, Martha P; Suarez, Carlos F; Varela, Yahson; Patarroyo, Manuel A; Bermudez, Adriana; Patarroyo, Manuel E

    2016-09-01

    Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche(-) rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche(+) orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory. PMID:27363338

  19. Prostacyclin induces a surprising long-lasting motility in quiescent uterine strips (indomethacin-treated) isolated from ovariectomized rats.

    PubMed

    Gimeno, A L; Chaud, M; Bonacossa, A; Franchi, A M; Gimeno, M F

    1983-10-01

    Dose-response curves for several prostaglandins (PGI2; PGD2; PGF2 and PGE2); BaCl2 or prostaglandin metabolites (15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha; 6-keto-PGF1 alpha and 6-keto PGE1 in quiescent (indomethacin-treated) uterine strips from ovariectomized rats, were constructed. All PGs tested as well as BaCl2, triggered at different concentrations, evident phasic contractions. Within the range of concentrations tested the portion of the curves for the metabolites of PGF2 alpha was shifted to the right of that for PGF2 alpha itself; the curve for 6-keto-PGF1 alpha was displaced to the right of the curve for PGI2 and that for 6-keto-PGE1 to the left. It was also demonstrated that the uterine motility elicited by 10(-5) M PGF2 alpha and its metabolites was long lasting (more than 3 hours) and so it was the activity evoked by PGI2;6-keto-PGF1 alpha and BaCl2, but not the contractions following 6-keto-PGE1, which disappeared much earlier. The contractile tension after PGF2 alpha; 15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha and PGI2, increased as time progressed whilst that evoked by 6-keto-PGF1 alpha or BaCl2 fluctuated during the same period around more constant levels. The surprising sustained and gradually increasing contractile activity after a single dose of an unstable prostaglandin such as PGI2, on the isolated rat uterus rendered quiescent by indomethacin, is discussed in terms of an effect associated to its transformation into more stable metabolites (6-keto-PGF1 alpha, or another not tested) or as a consequence of a factor which might protects prostacyclin from inactivation. PMID:6361911

  20. DISPARATE EVOLUTION OF RIGHT AND LEFT ATRIAL RATE DURING ABLATION OF LONG-LASTING PERSISTENT ATRIAL FIBRILLATION

    PubMed Central

    Hocini, Mélèze; Nault, Isabelle; Wright, Matthew; Veenhuyzen, George; Narayan, Sanjiv M.; Jaïs, Pierre; Lim, Kang-Teng; Knecht, Sébastien; Matsuo, Seiichiro; Forclaz, Andrei; Miyazaki, Shinsuke; Jadidi, Amir; O’Neill, Mark D.; Sacher, Frédéric; Clémenty, Jacques; Haïssaguerre, Michel

    2010-01-01

    Objectives To assess whether additional ablation in the right atrium(RA) improves termination rate in long-lasting persistent atrial fibrillation(PsAF). Background Prolongation of atrial fibrillation(AF) cycle length(CL) measured from the left atrial appendage predicts favorable outcome during catheter ablation of PsAF. However, in some patients despite prolongation of AFCL in the left atrium(LA) with ablation, AF persists. We hypothesized that this is due to RA drivers and these patients may benefit from RA ablation. Methods 148 consecutive patients undergoing catheter ablation of PsAF(duration 25±32 months) were studied. AFCL was monitored in both atria during stepwise ablation commencing in the LA. Ablation was performed in the RA when all LA sources in AF had been ablated and a RA-LA gradient existed. The procedural endpoint was AF termination. Results Two distinct patterns of AFCL change emerged during LA ablation. In 104patients(70%), there was parallel increase of AFCL in LA and RA culminating in AF termination (baseline: LA 153ms[140,170], RA 155ms[143,171]; after ablation: LA 181ms[170,200], RA 186ms[175,202]). In 24 patients(19%), RA AFCL did not prolong, creating a right-to-left frequency gradient, (baseline: LA 142ms[143,153], RA 145 ms[139,162]; after ablation: LA 177 ms[165–185], RA 152ms[147,175]). These patients had a longer AF history (23versus12 months, p=0.001), and larger RA diameter (42versus39mm, p=0.005) and RA ablation terminated AF in 55%. In the remaining 20 patients, biatrial ablation failed to terminate AF. Conclusions A divergent pattern of AFCL prolongation after LA ablation resulting in a right-to-left gradient demonstrating that the right atrium is driving AF in about 20 % of PsAF. PMID:20202517

  1. 7-oxo-PGI2 induced late appearing and long lasting antiischaemic and antiarrhythmic action in dogs.

    PubMed

    Végh, A; Udvary, E; Szekeres, L; Szilvássy, Z

    1988-01-01

    In our earlier experiments administration of the stable PGI2 analogue: 7-oxo-PGI2-ephedrine salt to dogs resulted in a late-appearing and long-lasting protection from coronary ligation induced ischaemia as well as from postocclusion and reperfusion arrhythmias. Objective of the present study was to evaluate the extent and duration of antiischaemic and antiarrhythmic action induced by a single dose 50 ug/kg i.m. 7-oxo-PGI2 in dogs subjected to myocardial ischaemia evoked by left anterior descending coronary artery (LAD) ligation at different intervals (2, 6, 24, 48, 72 hours and 2 weeks) after treatment. After anaesthesia and thoracotomy the electrophysiological parameters - sinus cycle length (SCL), corrected sinus node recovery time (CSNRT), atrial and ventricular functional refractory period (AFRP, VFRP), and atrio-ventricular effective refractory period (A-V ERP) - were determined by means of computer controlled programmed electrical stimulation. Then the animals were subjected to LAD occlusion for 25 minutes and subsequent reperfusion. 7-oxo-PGI2 pretreatment considerably protected against myocardial ischaemia i.e. there was significant reduction in ST-segment elevation, the number of extrasystoles (ES) and the incidence of ventricular fibrillation (VF). The antiischaemic action started 2 or 6 hours after the drug administration, however, the maximal protection - indicated by the diminution of ischaemic epicardial ST-segment elevation - as well as the most striking reduction in postocclusion and reperfusion arrhythmias could be observed 48 hours after the single dose of 7-oxo-PGI2 and in case of two weeks treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3073767

  2. A case study of ionospheric storm effects during long-lasting southward IMF Bz-driven geomagnetic storm

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Liu, Libo; Nakamura, Takuji; Zhao, Biqiang; Ning, Baiqi; Yoshikawa, A.

    2014-09-01

    Multiple instrumental observations including GPS total electron content (TEC), foF2 and hmF2 from ionosondes, vertical ion drift measurements from Communication/Navigation Outage Forecasting System, magnetometer data, and far ultraviolet airglow measured by Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics/Global Ultraviolet Imager (TIMED/GUVI) are used to investigate the profound ionospheric disturbances at midlatitude and low latitude during the 14-17 July 2012 geomagnetic storm event, which was featured by prolonged southward interplanetary geomagnetic field component for about 30 h below -10 nT. In the East Asian/Australian sector, latitudinal profile of TEC variations in the main phase were characterized by three bands of increments and separated by weak depressions in the equatorial ionospheric anomaly (EIA) crest regions, which were caused by the combined effects of disturbance dynamo electric fields (DDEF) and equatorward neutral winds. In the recovery phase, strong inhibition of EIA occurred and the summer crest of EIA disappeared on 16 July due to the combined effects of intrusion of neutral composition disturbance zone as shown by the TIMED/GUVI O/N2 measurements and long-lasting daytime westward DDEF inferred from the equatorial electrojet observations. The transit time of DDEF over the dip equator from westward to eastward is around 2200 LT. In the American longitude, the salient ionospheric disturbances in the summer hemisphere were characterized by daytime periodical intrusion of negative phase for three consecutive days in the recovery phase, preceded by storm-enhanced density plume in the initial phase. In addition, multiple short-lived prompt penetration electric fields appeared during stable southward interplanetary magnetic field (IMF) Bz in the recovery phase and were responsible for enhanced the EIA and equatorial ionospheric uplift around sunset.

  3. A case study of Ionospheric storm effects during long-lasting southward IMF Bz driven geomagnetic storm

    NASA Astrophysics Data System (ADS)

    Liu, J., Sr.

    2014-12-01

    Multiple instrumental observations including GPS TEC, foF2 and hmF2 from ionosondes, vertical ion drift measurements from C/NOFS, magnetometer data and far-ultraviolet airglow measured by TIMED/GUVI are used to investigate the profound ionospheric disturbances at mid- and low-latitudes during the 14-17 July 2012 geomagnetic storm event, which was featured by prolonged southward interplanetary geomagnetic field component for about 30 hours below -10 nT. In the East Asian/Australian sector, latitudinal profile of TEC variations in the main phase were characterized by three bands of increments and separated by weak depressions in the Equatorial Ionospheric Anomaly (EIA) crest regions, which were caused by the combined effects of disturbance dynamo electric fields (DDEF) and equatorward neutral winds. In the recovery phase, strong inhibition of EIA occurred and the summer crest of EIA disappeared on 16 July due to the combined effects of intrusion of neutral composition disturbance zone as shown by the TIME/GUVI O/N2 measurements and long-lasting daytime westward DDEF inferred from the equatorial electric electrojet (EEJ) observations. The transit time of DDEF over the dip equator from westward to eastward is around 2200 LT. In the American longitude, the salient ionospheric disturbances in the summer hemisphere were characterized by daytime periodical intrusion of negative phase for three consecutive days in the recovery phase, preceded by storm enhanced density (SED) plume in the initial phase. In addition, multiple short-lived prompt penetration electric fields (PPEF) appeared during stable southward IMF Bz in the recovery phase and were responsible for enhanced the EIA and equatorial ionospheric uplift around sunset.

  4. Cell-intrinsic gp130 Signaling on CD4+ T cells Shapes Long-lasting Antiviral Immunity

    PubMed Central

    Harker, James A.; Wong, Kurt A.; Dolgoter, Aleksandr; Zuniga, Elina I.

    2015-01-01

    The interleukin-6 (IL-6) cytokine family utilizes the common signal transduction molecule gp130, which can mediate a diverse range of outcomes. To clarify the role of gp130 signaling in vivo during acute viral infection we infected Cd4-cre Il6stfl/fl mice, in which gp130 is conditionally ablated in T cells, with acute lymphocytic choriomeningitis virus (LCMV). We found that by day 12, but not at day 8, post infection the number of virus specific CD4+ T cells was reduced in the absence of gp130, and this was sustained for up to 2 months post infection. Additionally gp130 deficient TFH had lower expression of Maf, IL-21 and ICOS and this was accompanied by a reduction in the proportion of germinal center B cells and plasmablasts. Remarkably, two months post-infection the proportion of IgG2a/c+ memory B cells and the systemic levels of LCMV-specific IgG2 Abs were dramatically decreased, while there was a corresponding increase in IgG1+ memory B cells and virus-specific IgG1 Abs. In the same animals Gp130 deficient virus specific CD8+ T cells showed a reduced proportion of memory cells, which expressed lower levels of Tcf7, and displayed diminished recall responses on secondary infection. Mixed bone marrow chimeras revealed that the aforementioned gp130 effects on CD4+ T cells were cell-intrinsic. Overall our data show that gp130 signaling in T cells influences the quantity and quality of long lasting CD4+ T cell responses as well as CD8+ T cell and antibody mediated immunity after acute viral infection. PMID:26085685

  5. Lesions of the basolateral amygdala reverse the long-lasting interference with shuttle box escape produced by uncontrollable stress

    PubMed Central

    Greenwood, Benjamin N.; Strong, Paul V.; Fleshner, Monika

    2010-01-01

    Exposure to an uncontrollable, but not a controllable, stressor produces a constellation of behaviors called learned helplessness. In rodents, uncontrollable stress interferes with the ability to learn to escape from escapable shocks delivered in a shuttle box. The stress-induced shuttle box escape deficit is a common screening tool for potential antidepressant strategies. Inconsistencies in the literature exist regarding the time-course of, and mechanisms underlying, stress-induced escape deficits. When no common cues are shared between the stressor and testing environment, the escape deficit is short lived and independent of conditioned freezing. In contrast, when stress and testing occur in the same or similar environments, the escape deficit is very long-lasting. The current studies address the hypothesis that the long-lived escape deficit produced by uncontrollable stress is dependent upon conditioned fear and the basolateral amygdala (BLA). Rats received bilateral excitotoxic lesions of the BLA 2 wk following uncontrollable foot shocks. One wk after surgery, rats were tested for conditioned freezing and escape behavior in the same shuttle boxes in which prior foot shocks were delivered. Stressed rats with sham lesions displayed robust conditioned freezing and failed to escape during shuttle box testing. Lesions of the BLA eliminated conditioned freezing and completely restored stressed rats' ability to perform the escape contingency. These data indicate that the long-lived stress-induced escape deficit produced under conditions in which the stressor and testing environments share common cues is dependent upon conditioned freezing elicited by the BLA. Results have important implications for the mechanisms underlying learned helplessness phenomena. PMID:20226213

  6. Excitotoxic Insult Results in a Long-Lasting Activation of CaMKIIα and Mitochondrial Damage in Living Hippocampal Neurons

    PubMed Central

    Otmakhov, Nikolai; Gorbacheva, Elena V.; Regmi, Shaurav; Yasuda, Ryohei; Hudmon, Andy; Lisman, John

    2015-01-01

    Over-activation of excitatory NMDA receptors and the resulting Ca2+ overload is the main cause of neuronal toxicity during stroke. CaMKII becomes misregulated during such events. Biochemical studies show either a dramatic loss of CaMKII activity or its persistent autonomous activation after stroke, with both of these processes being implicated in cell toxicity. To complement the biochemical data, we monitored CaMKII activation in living hippocampal neurons in slice cultures using high spatial/temporal resolution two-photon imaging of the CaMKIIα FRET sensor, Camui. CaMKII activation state was estimated by measuring Camui fluorescence lifetime. Short NMDA insult resulted in Camui activation followed by a redistribution of its protein localization: an increase in spines, a decrease in dendritic shafts, and concentration into numerous clusters in the cell soma. Camui activation was either persistent (> 1–3 hours) or transient (~20 min) and, in general, correlated with its protein redistribution. After longer NMDA insult, however, Camui redistribution persisted longer than its activation, suggesting distinct regulation/phases of these processes. Mutational and pharmacological analysis suggested that persistent Camui activation was due to prolonged Ca2+ elevation, with little impact of autonomous states produced by T286 autophosphorylation and/or by C280/M281 oxidation. Cell injury was monitored using expressible mitochondrial marker mito-dsRed. Shortly after Camui activation and clustering, NMDA treatment resulted in mitochondrial swelling, with persistence of the swelling temporarily linked to the persistence of Camui activation. The results suggest that in living neurons excitotoxic insult produces long-lasting Ca2+-dependent active state of CaMKII temporarily linked to cell injury. CaMKII function, however, is to be restricted due to strong clustering. The study provides the first characterization of CaMKII activation dynamics in living neurons during excitotoxic

  7. Long lasting increase in nociceptive threshold induced in mice by forced swimming: involvement of an endorphinergic mechanism.

    PubMed

    Suaudeau, C; Costentin, J

    2000-05-01

    Mice submitted to forced swimming session(s) displayed a long lasting modification in their nociceptive threshold, assessed through their jump latency from a hot plate (55 degrees C). Thus two forced swimming sessions (6 min each, 8h apart), in water at 33 degrees C, increased by about 50% the jump latency when the hot plate test was performed 14 hours, 3 days or 6 days thereafter. The water temperature (16 degrees C vs 33 degrees C) had no critical influence in this respect. To be clearly effective (at 33 degrees C) the swimming session had to be performed twice (when performed only once it was irregularly effective); it apparently culminated for a 6 min duration, since its effectiveness was not significantly increased by extending the swimming time to 12 min or 18 min. Performing 2 forced swimming sessions (6 min each, 8h apart), 5 consecutive days, resulted in a suppression of the increase in jump latency in the hot plate test. The two forced swimming episodes-induced analgesia was prevented by the s.c. administration of diazepam (from 0.125 mg/kg) or morphine (from 5 mg/kg) or scopolamine (1 mg/kg) before each forced swimming episode. Morphine (7.5 mg/kg) was uneffective to prevent the induction of two forced swimming episodes-induced analgesia when it was administered immediately after each forced swimming session. Finally this analgesia was dose dependently reversed by naloxone (ID(50) = 0.14 mg/kg, s.c., 30 min before the hot plate test). It is hypothesized that the handling of mice immediately before the hot plate test induces the remembrance of the stress induced by previous forced swimming episodes, triggering a fear reaction which increases the nociceptive threshold. PMID:10938583

  8. RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions.

    PubMed

    Broad, John; Takahashi, Nobuyuki; Tajimi, Masaomi; Sudo, Masaki; Góralczyk, Adam; Parampalli, Umesh; Mannur, Kesava; Yamamoto, Toshinori; Sanger, Gareth J

    2016-02-01

    The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 μM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 μM this activity was usually prolonged. At higher concentrations (3-30 μM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 μM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying. PMID:26685754

  9. TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects.

    PubMed

    Gatto, Gregory J; Bohme, G Andrees; Caldwell, William S; Letchworth, Sharon R; Traina, Vincent M; Obinu, M Carmen; Laville, Michel; Reibaud, Michel; Pradier, Laurent; Dunbar, Geoffrey; Bencherif, Merouane

    2004-01-01

    The development of selective ligands targeting neuronal nicotinic acetylcholine receptors to alleviate symptoms associated with neurodegenerative diseases presents the advantage of affecting multiple deficits that are the hallmarks of these pathologies. TC-1734 is an orally active novel neuronal nicotinic agonist with high selectivity for neuronal nicotinic receptors. Microdialysis studies indicate that TC-1734 enhances the release of acetylcholine from the cortex. TC-1734, by either acute or repeated administration, exhibits memory enhancing properties in rats and mice and is neuroprotective following excitotoxic insult in fetal rat brain in cultures and against alterations of synaptic transmission induced by deprivation of glucose and oxygen in hippocampal slices. At submaximal doses, TC-1734 produced additive cognitive effects when used in combination with tacrine or donepezil. Unlike (-)-nicotine, behavioral sensitization does not develop following repeated administration of TC-1734. Its pharmacokinetic (PK) profile (half-life of 2 h) contrasts with the long lasting improvement in working memory (18 h) demonstrating that cognitive improvement extends beyond the lifetime of the compound. The very low acute toxicity of TC-1734 and its receptor activity profile provides additional mechanistic basis for its suggested potential as a clinical candidate. TC-1734 was very well tolerated in acute and chronic oral toxicity studies in mice, rats and dogs. Phase I clinical trials demonstrated TC-1734's favorable pharmacokinetic and safety profile by acute oral administration at doses ranging from 2 to 320 mg. The bioavailability, pharmacological, pharmacokinetic, and safety profile of TC-1734 provides an example of a safe, potent and efficacious neuronal nicotinic modulator that holds promise for the management of the hallmark symptomatologies observed in dementia. PMID:15179444

  10. Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity.

    PubMed

    Knikou, Maria; Dixon, Luke; Santora, Danielle; Ibrahim, Mohamed M

    2015-09-01

    Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans. PMID:26108955

  11. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family-crucially involved in the regulation of brain structural plasticity and cognitive processes-can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R. PMID:25926782

  12. Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain

    PubMed Central

    Bonnard, Elisabeth; Poras, Hervé; Nadal, Xavier; Maldonado, Rafael; Fournié-Zaluski, Marie-Claude; Roques, Bernard P

    2015-01-01

    The peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain generation as suggested by the modulation of opioid receptors expression and enkephalins (ENKs) release observed in these painful conditions. Accordingly, an innovative approach in the treatment of these nocifensive events is to increase and maintain high local concentrations of extracellular pain-evoked ENKs, by preventing their physiological enzymatic inactivation by two Zn metallopeptidases, the neutral endopeptidase (NEP, neprilysin, EC 3.4.24.11) and the neutral aminopeptidase (APN, EC 3.4.11.2). With this aim, new orally active dual ENKephalinase inhibitors (DENKIs) were designed as soluble prodrugs by introducing a N-terminal cleavable carbamate in the previously described aminophosphinic inhibitors. This induces long-lasting antinociceptive responses after oral administration, in various rodent models of inflammatory and neuropathic pain. These responses are mediated through stimulation of peripheral opioid receptors by DENKIs-protected ENKs as demonstrated by naloxone methiodide reversion. In all tested models, the most efficient prodrug 2a (PL265) was active, at least during 150–180 min, after single oral administration of 25–50 mg/kg in mice and of 100–200 mg/kg in rats. In models of neuropathic pain, both hyperalgesia and allodynia were markedly reduced. Interestingly, combination of inactive doses of 2a (PL265) and of the anti-epileptic drug gabapentin had synergistic effect on neuropathic pain. Pharmacokinetic studies of 2a (PL265) in rats show that the active drug is the only generated metabolite produced. These encouraging results have made 2a (PL265) a suitable candidate for clinical development. PMID:25692029

  13. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

    PubMed Central

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family—crucially involved in the regulation of brain structural plasticity and cognitive processes—can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R. PMID:25926782

  14. Long lasting preventive effects of piperlongumine and a Piper longum extract against stress triggered pathologies in mice

    PubMed Central

    Yadav, Vaishali; Chatterjee, Shyam Sunder; Majeed, Muhammed; Kumar, Vikas

    2015-01-01

    Aim: To compare doxycycline (DOX) such as oral efficacies of piperlongumine (PL) and a Piper longum fruits extract (PLE) as stress resistance inducers. Materials and Methods: Efficacies of oral pretreatments with 5 mg/kg PL or PLE or of 50 mg/kg DOX for 10 consecutive days against stress resistance were compared. Mice in treated groups were subjected to a stress induced hyperthermia on the 1st, 5th, 7th, and 10thday. Treated mice were then subjected to tail suspension test on the 11thday. Alteration in body weights, core temperatures, and gastric ulcers triggered by occasional exposures to foot shocks were determined. Results: DOX like long-lasting protective effects of PL and PLE against gradual alterations in body weights, basal temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed 1 day after the last foot-shock exposures and gastric ulcers and other pathologies quantified 1 day after the test were also suppressed in PL or PLE or DOX pretreated groups. Conclusion: PL and crude PLE are DOX like long-acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of P. longum and other plants of the Piperaceae family, and reveal that PL is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant-derived products enriched in PL or piperine like amide alkaloids in volunteers and patients can be warranted. PMID:26649232

  15. Enzymatic mono-pegylation of glucagon-like peptide 1 towards long lasting treatment of type 2 diabetes

    PubMed Central

    Selis, Fabio; Schrepfer, Rodolfo; Sanna, Riccardo; Scaramuzza, Silvia; Tonon, Giancarlo; Dedoni, Simona; Onali, Pierluigi; Orsini, Gaetano; Genovese, Stefano

    2012-01-01

    Human glucagon-like peptide-1 (GLP-1) is a physiological gastrointestinal peptide with glucose-dependent insulinotropic effects which is therefore considered an interesting antidiabetic agent. However, after in vivo administration, exogenous GLP-1 does not exert its physiological action due to the combination of rapid proteolytic degradation by ubiquitous dipeptidyldipeptidase IV (DPP IV) enzyme and renal clearance resulting in an extremely short circulating half-life. In this work we describe the conjugation of GLP-1-(7-36)-amide derivatives with polyethylene glycol (PEG) by enzymatic site-specific transglutamination reaction as an approach to reduce both the proteolysis and the renal clearance rates. The compound GLP-1-(7-36)-amide-Q23-PEG 20 kDa monopegylated on the single glutamine residue naturally present in position 23 maintained the ability to activate the GLP-1 receptor expressed in the rat β-cell line RIN-m5F with nanomolar potency along with an increased in vitro resistance to DDP IV and a circulating half-life of about 12 h after subcutaneous administration in rats. These properties enabled GLP-(7-36)-amide-Q23-PEG 20 kDa to exert a glucose-stabilizing effect for a period as long as 8 h, as demonstrated by a single subcutaneous injection to diabetic mice concomitantly challenged with an oral glucose load. The results reported in this work indicate that GLP-(7-36)-amide-Q23-PEG 20 kDa could be a lead compound for the development of long-lasting anti-diabetic agents useful in the treatment of type 2 diabetes affected patients. PMID:25755995

  16. Proteases as Insecticidal Agents

    PubMed Central

    Harrison, Robert L.; Bonning, Bryony C.

    2010-01-01

    Proteases from a variety of sources (viruses, bacteria, fungi, plants, and insects) have toxicity towards insects. Some of these insecticidal proteases evolved as venom components, herbivore resistance factors, or microbial pathogenicity factors, while other proteases play roles in insect development or digestion, but exert an insecticidal effect when over-expressed from genetically engineered plants or microbial pathogens. Many of these proteases are cysteine proteases, although insect-toxic metalloproteases and serine proteases have also been examined. The sites of protease toxic activity range from the insect midgut to the hemocoel (body cavity) to the cuticle. This review discusses these insecticidal proteases along with their evaluation and use as potential pesticides. PMID:22069618

  17. Inflammation and neurological adverse drugs reactions: a case of long lasting impaired consciousness after oxatomide administration in a patient with gastroenteritis

    PubMed Central

    2012-01-01

    Oxatomide at therapeutic doses generates occasionally drowsiness in children. When administered at toxic doses, however oxatomide may induce long lasting impaired consciousness. We now report a case of severe long lasting impaired consciousness induced by therapeutic doses of oxatomide occurring in a child affected by acute gastroenteritis. The clinical symptoms, the pharmacogenetic tests of polymorphisms in cytochrome P450 metabolizing enzymes (CYPs) and the clinical and laboratory analyses indicate that the enhanced drug sedative effect is likely due to an acute, yet mild, inflammatory state of the patient. These findings highlight the importance of assessing common, not serious inflammatory states when oxatomide is prescribed in paediatric patients. PMID:22464080

  18. Triple insecticide resistance in Anopheles culicifacies: a practical impediment for malaria control in Odisha State, India

    PubMed Central

    Sahu, S.S.; Gunasekaran, K.; Vijayakumar, T.; Jambulingam, P.

    2015-01-01

    Background & objectives: In Odisha State, the control of malaria vectors has become dependent on synthetic pyrethroids, which are used for treatment of all approved long-lasting insecticidal nets (LLINs). The vast use of just one class of insecticide has led to the problem of resistance to insecticides in malaria vectors. One of the major malaria vectors in Odisha State is Anopheles culicifacies Giles. The aim of this study was to determine the resistance status of An. culicifacies to deltamethrin, a synthetic pyrethroid and other common insecticides used by the National Vector Borne Diseases Control Programme (NVBDCP) for indoor residual spraying in Odisha State. Methods: Mosquitoes were collected during April 2014 - June 2014 from 15 randomly selected villages in five Plasmodium falciparum endemic southern districts of Odisha State. The blood-fed wild caught females were exposed to the diagnostic dosage of DDT (4.0%), malathion (5.0%) and deltamethrin (0.05%) for one hour. Mortality was recorded at 24 h after the exposure. Results: Results indicated that An. culicifacies was resistant to all the three insecticides used in the malaria control programme in the five districts of Odisha State. Interpretation & conclusions: Resistance management strategy by appropriate rotation of different groups of insecticides including carbamates and incorporating a synergist with synthetic pyrethroids for treating mosquito nets should be considered for the control of malaria vectors in the area, especially where An. culicifacies is predominant. Periodical monitoring of susceptibility/resistance status of An. culicifacies to different insecticides is warranted. PMID:26905243

  19. Robotic guidance induces long-lasting changes in the movement pattern of a novel sport-specific motor task.

    PubMed

    Kümmel, Jakob; Kramer, Andreas; Gruber, Markus

    2014-12-01

    Facilitating the learning or relearning of motor tasks is one of the main goals of coaches, teachers and therapists. One promising way to achieve this goal is guiding the learner through the correct movement trajectory with the help of a robotic device. The aim of this study was to investigate if haptic guidance can induce long-lasting changes in the movement pattern of a complex sport-specific motor task. For this purpose, 31 subjects were assigned to one of three groups: EA (early angle, n=10), LA (late angle, n=11) and CON (control, n=10). EA and LA successfully completed five training sessions, which consisted of 50 robot-guided golf swings and 10 free swings each, whereas CON had no training. The EA group was guided through the movement with the wrist being bent early during backswing, whereas in the LA group it was bent late. The participants of EA and LA were not told about this difference in the movement patterns. To assess if the robot-guided training was successful in shaping the movement pattern, the timing of the wrist bending during the backswing in free swings was measured before (PRE), one day after (POST), and 7 days after (FUP) the five training sessions. The ANOVA (time×group×angle) showed that during POST and FUP, the participants of the EA group bent their wrist significantly earlier during the backswing than the other groups. Post-hoc analyses revealed that this interaction effect was mainly due to the differences in the wrist angle progression during the first 5° of the backswing. The robot-guided training was successful in shaping the movement pattern, and these changes persisted even after 7 days without further practice. This might have implications for the learning of complex motor tasks in general, as haptic guidance might quickly provide the beginner with an internal model of the correct movement pattern without having to direct the learner's attention towards the key points of the correct movement pattern. PMID:25238621

  20. Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

    PubMed

    Sikiric, P; Jadrijevic, S; Seiwerth, S; Sosa, T; Deskovic, S; Perovic, D; Aralica, G; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Ziger, T; Rotkvic, I; Mise, S; Zoricic, I; Sebecic, B; Patrlj, L; Kocman, B; Sarlija, M; Mikus, D; Separovic, J; Hanzevacki, M; Gjurasin, M; Miklic, P

    1999-12-01

    values, BPC 157-treated groups consistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated groups showed no difference compared with control values. Thus, despite limitations, a generalization supporting a direct importance of a common cytoprotective approach, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions. PMID:10672991

  1. Insecticides and Biological Control

    ERIC Educational Resources Information Center

    Furness, G. O.

    1972-01-01

    Use of insecticides has been questioned due to their harmful effects on edible items. Biological control of insects along with other effective practices for checking spread of parasites on crops are discussed. (PS)

  2. Electrostatic coating enhances bioavailability of insecticides and breaks pyrethroid resistance in mosquitoes

    PubMed Central

    Andriessen, Rob; Snetselaar, Janneke; Suer, Remco A.; Osinga, Anne J.; Deschietere, Johan; Lyimo, Issa N.; Mnyone, Ladslaus L.; Brooke, Basil D.; Ranson, Hilary; Knols, Bart G. J.; Farenhorst, Marit

    2015-01-01

    Insecticide resistance poses a significant and increasing threat to the control of malaria and other mosquito-borne diseases. We present a novel method of insecticide application based on netting treated with an electrostatic coating that binds insecticidal particles through polarity. Electrostatic netting can hold small amounts of insecticides effectively and results in enhanced bioavailability upon contact by the insect. Six pyrethroid-resistant Anopheles mosquito strains from across Africa were exposed to similar concentrations of deltamethrin on electrostatic netting or a standard long-lasting deltamethrin-coated bednet (PermaNet 2.0). Standard WHO exposure bioassays showed that electrostatic netting induced significantly higher mortality rates than the PermaNet, thereby effectively breaking mosquito resistance. Electrostatic netting also induced high mortality in resistant mosquito strains when a 15-fold lower dose of deltamethrin was applied and when the exposure time was reduced to only 5 s. Because different types of particles adhere to electrostatic netting, it is also possible to apply nonpyrethroid insecticides. Three insecticide classes were effective against strains of Aedes and Culex mosquitoes, demonstrating that electrostatic netting can be used to deploy a wide range of active insecticides against all major groups of disease-transmitting mosquitoes. Promising applications include the use of electrostatic coating on walls or eave curtains and in trapping/contamination devices. We conclude that application of electrostatically adhered particles boosts the efficacy of WHO-recommended insecticides even against resistant mosquitoes. This innovative technique has potential to support the use of unconventional insecticide classes or combinations thereof, potentially offering a significant step forward in managing insecticide resistance in vector-control operations. PMID:26324912

  3. Electrostatic coating enhances bioavailability of insecticides and breaks pyrethroid resistance in mosquitoes.

    PubMed

    Andriessen, Rob; Snetselaar, Janneke; Suer, Remco A; Osinga, Anne J; Deschietere, Johan; Lyimo, Issa N; Mnyone, Ladslaus L; Brooke, Basil D; Ranson, Hilary; Knols, Bart G J; Farenhorst, Marit

    2015-09-29

    Insecticide resistance poses a significant and increasing threat to the control of malaria and other mosquito-borne diseases. We present a novel method of insecticide application based on netting treated with an electrostatic coating that binds insecticidal particles through polarity. Electrostatic netting can hold small amounts of insecticides effectively and results in enhanced bioavailability upon contact by the insect. Six pyrethroid-resistant Anopheles mosquito strains from across Africa were exposed to similar concentrations of deltamethrin on electrostatic netting or a standard long-lasting deltamethrin-coated bednet (PermaNet 2.0). Standard WHO exposure bioassays showed that electrostatic netting induced significantly higher mortality rates than the PermaNet, thereby effectively breaking mosquito resistance. Electrostatic netting also induced high mortality in resistant mosquito strains when a 15-fold lower dose of deltamethrin was applied and when the exposure time was reduced to only 5 s. Because different types of particles adhere to electrostatic netting, it is also possible to apply nonpyrethroid insecticides. Three insecticide classes were effective against strains of Aedes and Culex mosquitoes, demonstrating that electrostatic netting can be used to deploy a wide range of active insecticides against all major groups of disease-transmitting mosquitoes. Promising applications include the use of electrostatic coating on walls or eave curtains and in trapping/contamination devices. We conclude that application of electrostatically adhered particles boosts the efficacy of WHO-recommended insecticides even against resistant mosquitoes. This innovative technique has potential to support the use of unconventional insecticide classes or combinations thereof, potentially offering a significant step forward in managing insecticide resistance in vector-control operations. PMID:26324912

  4. Tonic contraction of canine gastric muscle during long-lasting calcium removal and its dependence on magnesium.

    PubMed

    Filipponi, K; Golenhofen, K; Hofstetter, V; Hohnsbein, J; Lammel, E; Lukanow, J

    1987-12-01

    1. Tonic contractions induced by acetylcholine (ACh) in canine gastric fundus preparations were shown to persist during long-lasting exposure to Ca2+-free solution containing EGTA (1 mmol/l). These EGTA-resistant contractions amounted to up to more than 50% of maximal ACh-control responses in physiological salt solution. They could be evoked repeatedly for more than 20 h without reduction in size, each contraction lasting as long as ACh was present. 2. During prolonged exposure to Ca2+-free solution at normal Mg2+ concentration ([Mg2+]O = 1.2 mmol/l), the preparations exhibited a slowly developing contracture (elevation of the baseline of contraction), which was particularly pronounced in strips taken from the circular layer of the muscular wall (44% of control ACh-maximum after 4 h in Ca2+-free solution). Contracture could be suppressed either by increasing [Mg2+]O to 6-10 mmol/l or by depolarizing the cell membrane (replacement of external Na+ by K+). However, contracture also developed if, at physiological [Na+]O and [K+]O, [Mg2+]O was further increased to 50 mmol/l. 3. The combined effects of [Mg2+]O and membrane potential suggest that contracture is caused by a gain of Mg2+ by the cells. This conclusion is based on the assumption that (a) the cytoplasmic Mg2+ concentration is determined by the transmembrane electrochemical gradient acting on Mg2+, the magnesium permeability of the cell membrane (PMg) and an active extrusion mechanism, and that (b) Ca2+ removal leads to an increase of PMg which is (partly) prevented by an appropriate increase of [Mg2+]O. 4. 45Ca efflux experiments, performed at [Mg2+]O = 10 mmol/l to avoid interference of ACh responses with contracture, showed that the cellular 45Ca content decreased from some 200 mumol/kg wet wt. to less than 10 mumol/kg wet wt. within 10-20 h in Ca2+-free solution. Activations by ACh did not produce any detectable increase in 45Ca efflux. 5. The calcium ionophore A23187 (10(-5) mol/l), applied in order to

  5. Long-Lasting Impact of Neonatal Exposure to Total Body Gamma Radiation on Secondary Lymphoid Organ Structure and Function.

    PubMed

    Rangel-Moreno, Javier; de la Luz Garcia-Hernandez, Maria; Ramos-Payan, Rosalio; Biear, Jamie; Hernady, Eric; Sangster, Mark Y; Randall, Troy D; Johnston, Carl J; Finkelstein, Jacob N; Williams, Jacqueline P

    2015-10-01

    population, and used the induction of adaptive immunity against influenza virus as a functional end point. We demonstrated that, in adult animals irradiated as neonates, high endothelial venule (HEV) expansion, generation of follicular helper T cells (TFH) and formation of splenic germinal centers (GC) were rapidly and, more importantly, persistently impaired in SLO, suggesting that the early-life exposure to sublethal radiation had long-lasting effects on the induction of humoral immunity. Although the neonatal TBI did not affect the overall outcome from influenza infection in the adults at the earlier time points assessed, we believe that they nonetheless contribute significantly to the increased mortality observed at subsequent late time points. Furthermore, we speculate that the detrimental and persistent impact on the induction of CD4 T- and B-cell responses in the mediastinal lymph nodes will decrease the animals' ability to respond to other aerial pathogens. Since many of these pathogens are normally cleared by antibodies, our findings provide an explanation for the susceptibility of survivors of childhood HCT to life-threatening respiratory tract infections. These findings have implications regarding the need for increased monitoring in pediatric hematopoietic cell transplant patients, since they indicate that there are ongoing and cumulative defects in SLO, which, importantly, develop during the immediate and early postirradiation period when patients may appear immunologically competent. The identification of changes in immune-related signals may offer bioindicators of progressive dysfunction, and of potential mechanisms that could be targeted so as to reduce the risk of infection from extracellular pathogens. Furthermore, these results support the potential susceptibility of the pediatric population to infection after sublethal irradiation in the context of a nuclear or radiological event. PMID:26397175

  6. Organophosphorus Insecticide Pharmacokinetics

    SciTech Connect

    Timchalk, Charles

    2010-01-01

    This chapter highlights a number of current and future applications of pharmacokinetics to assess organophosphate (OP) insecticide dosimetry, biological response and risk in humans exposed to these agents. Organophosphates represent a large family of pesticides where insecticidal as well as toxicological mode of action is associated with their ability to target and inhibit acetylcholinesterase (AChE). Pharmacokinetics entails the quantitative integration of physiological and metabolic processes associated with the absorption, distribution, metabolism and excretion (ADME) of drugs and xenobiotics. Pharmacokinetic studies provide important data on the amount of toxicant delivered to a target site as well as species-, age-, gender-specific and dose-dependent differences in biological response. These studies have been conducted with organophosphorus insecticides in multiple species, at various dose levels, and across different routes of exposure to understand their in vivo pharmacokinetics and how they contribute to the observed toxicological response. To access human exposure to organophosphorus insecticides, human pharmacokinetic studies have been conducted and used to develop biological monitoring strategies based on the quantitation of key metabolites in biological fluids. Pharmacokinetic studies with these insecticides are also useful to facilitate extrapolation of dosimetry and biological response from animals to humans and for the assessment of human health risk. In this regard, physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models are being utilized to assess risk and understand the toxicological implications of known or suspected exposures to various insecticides. In this chapter a number of examples are presented that illustrate the utility and limitation of pharmacokinetic studies to address human health concerns associated with organophosphorus insecticides.

  7. Insecticide Resistance in Fleas.

    PubMed

    Rust, Michael K

    2016-01-01

    Fleas are the major ectoparasite of cats, dogs, and rodents worldwide and potential vectors of animal diseases. In the past two decades the majority of new control treatments have been either topically applied or orally administered to the host. Most reports concerning the development of insecticide resistance deal with the cat flea, Ctenocephalides felis felis. Historically, insecticide resistance has developed to many of the insecticides used to control fleas in the environment including carbamates, organophosphates, and pyrethroids. Product failures have been reported with some of the new topical treatments, but actual resistance has not yet been demonstrated. Failures have often been attributed to operational factors such as failure to adequately treat the pet and follow label directions. With the addition of so many new chemistries additional monitoring of flea populations is needed. PMID:26999217

  8. Insecticide Resistance in Fleas

    PubMed Central

    Rust, Michael K.

    2016-01-01

    Fleas are the major ectoparasite of cats, dogs, and rodents worldwide and potential vectors of animal diseases. In the past two decades the majority of new control treatments have been either topically applied or orally administered to the host. Most reports concerning the development of insecticide resistance deal with the cat flea, Ctenocephalides felis felis. Historically, insecticide resistance has developed to many of the insecticides used to control fleas in the environment including carbamates, organophosphates, and pyrethroids. Product failures have been reported with some of the new topical treatments, but actual resistance has not yet been demonstrated. Failures have often been attributed to operational factors such as failure to adequately treat the pet and follow label directions. With the addition of so many new chemistries additional monitoring of flea populations is needed. PMID:26999217

  9. EFFICACY DATA OF CYANTRANILIPROLE CONTAINING INSECTICIDE PREPARATION ON CABBAGE ROOT FLY (DELIA RADICUM LINNAEUS) IN WINTER OILSEED RAPE.

    PubMed

    Farkas, I; Molnár, I; Somlyay, I; Tóth, E

    2015-01-01

    The increasing pressure of oilseed rape pests emphasized the need to improve the insecticide portfolio, i.e. register new active ingredients with new insecticide mode of action. The tested seed treatment formulation applied at 32; 40 and 50 UAT rate of containing cyantraniliprole as active substance. 40 UAT rate gives acceptable control of the Cabbage root fly in each trial. Despite the long lasting flight and egg laying period of cabbage root fly, the standard control products and also this product give 50-65% efficacy. It is enough to reduce damage of the Cabbage root fly and prevent economical damage in oilseed rape. PMID:27145579

  10. Hippocampal Injections of Oligomeric Amyloid β-peptide (1–42) Induce Selective Working Memory Deficits and Long-lasting Alterations of ERK Signaling Pathway

    PubMed Central

    Faucher, Pierre; Mons, Nicole; Micheau, Jacques; Louis, Caroline; Beracochea, Daniel J.

    2016-01-01

    Increasing evidence suggests that abnormal brain accumulation of soluble rather than aggregated amyloid-β1–42 oligomers (Aβo(1–42)) plays a causal role in Alzheimer’s disease (AD). However, as yet, animal’s models of AD based on oligomeric amyloid-β1–42 injections in the brain have not investigated their long-lasting impacts on molecular and cognitive functions. In addition, the injections have been most often performed in ventricles, but not in the hippocampus, in spite of the fact that the hippocampus is importantly involved in memory processes and is strongly and precociously affected during the early stages of AD. Thus, in the present study, we investigated the long-lasting impacts of intra-hippocampal injections of oligomeric forms of Aβo(1–42) on working and spatial memory and on the related activation of ERK1/2. Indeed, the extracellular signal-regulated kinase (ERK) which is involved in memory function had been found to be activated by amyloid peptides. We found that repeated bilateral injections (1injection/day over 4 successive days) of oligomeric forms of Aβo(1–42) into the dorsal hippocampus lead to long-lasting impairments in two working memory tasks, these deficits being observed 7 days after the last injection, while spatial memory remained unaffected. Moreover, the working memory deficits were correlated with sustained impairments of ERK1/2 activation in the medial prefrontal cortex (mPFC) and the septum, two brain areas tightly connected with the hippocampus and involved in working memory. Thus, our study is first to evidence that sub-chronic injections of oligomeric forms of Aβo(1–42) into the dorsal hippocampus produces the main sign of cognitive impairments corresponding to the early stages of AD, via long-lasting alterations of an ERK/MAPK pathway in an interconnected brain networks. PMID:26793098

  11. Long-Lasting Effects of Early-Life Antibiotic Treatment and Routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs

    PubMed Central

    Schokker, Dirkjan; Zhang, Jing; Vastenhouw, Stéphanie A.; Heilig, Hans G. H. J.; Smidt, Hauke; Rebel, Johanna M. J.; Smits, Mari A.

    2015-01-01

    Background In intensive pig husbandry systems, antibiotics are frequently administrated during early life stages to prevent respiratory and gastro-intestinal tract infections, often in combination with stressful handlings. The immediate effects of these treatments on microbial colonization and immune development have been described recently. Here we studied whether the early life administration of antibiotics has long-lasting effects on the pig’s intestinal microbial community and on gut functionality. Methodology/Principal Findings To investigate the long-lasting effect of early-life treatment, piglets were divided into three different groups receiving the following treatments: 1) no antibiotics and no stress, 2) antibiotics and no stress, and 3) antibiotics and stress. All treatments were applied at day four after birth. Sampling of jejunal content for community scale microbiota analysis, and jejunal and ileal tissue for genome-wide transcription profiling, was performed at day 55 (~8 weeks) and day 176 (~25 weeks) after birth. Antibiotic treatment in combination with or without exposure to stress was found to have long-lasting effects on host intestinal gene expression involved in a multitude of processes, including immune related processes. Conclusions/Significance The results obtained in this study indicate that early life (day 4 after birth) perturbations have long-lasting effects on the gut system, both in gene expression (day 55) as well as on microbiota composition (day 176). At day 55 high variance was observed in the microbiota data, but no significant differences between treatment groups, which is most probably due to the newly acquired microbiota during and right after weaning (day 28). Based on the observed difference in gene expression at day 55, it is hypothesized that due to the difference in immune programming during early life, the systems respond differently to the post-weaning newly acquired microbiota. As a consequence, the gut systems of

  12. miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

    NASA Astrophysics Data System (ADS)

    Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

    2014-02-01

    Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

  13. In Vivo and Ex Vivo Imaging Reveals a Long-Lasting Chlamydial Infection in the Mouse Gastrointestinal Tract following Genital Tract Inoculation

    PubMed Central

    Zhang, Qi; Huang, Yumeng; Gong, Siqi; Yang, Zhangsheng; Sun, Xin; Schenken, Robert

    2015-01-01

    Intravaginal infection with Chlamydia muridarum in mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected with C. trachomatis. Here, we utilized in vivo imaging of C. muridarum infection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. Unexpectedly, the C. muridarum-derived signal was still detectable in the abdominal area 100 days after inoculation. Ex vivo imaging of the mouse organs revealed that the long-lasting presence of the chlamydial signal was restricted to the gastrointestinal (GI) tract, which was validated by directly measuring the chlamydial live organisms and genomes in the same organs. The C. muridarum organisms spreading from the genital to the GI tracts were detected in different mouse strains and appeared to be independent of oral or rectal routes. Mice prevented from orally taking up excretions also developed the long-lasting GI tract infection. Inoculation of C. muridarum directly into the upper genital tract, which resulted in a delayed vaginal shedding of live organisms, accelerated the chlamydial spreading to the GI tract. Thus, we have demonstrated that the genital tract chlamydial organisms may use a systemic route to spread to and establish a long-lasting infection in the GI tract. The significance of the chlamydial spreading from the genital to GI tracts is discussed. PMID:26099591

  14. Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity

    PubMed Central

    Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2013-01-01

    The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long-term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75NTR pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75NTR pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75NTR-masking conditions, thus supporting the aforementioned hypothesis. PMID:24212565

  15. Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity

    NASA Astrophysics Data System (ADS)

    Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

    2013-11-01

    The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long-term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75NTR pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75NTR pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75NTR-masking conditions, thus supporting the aforementioned hypothesis.

  16. METABOLISM OF CARBAMATE INSECTICIDES

    EPA Science Inventory

    The results of studies conducted to determine the metabolic fate of carbamate insecticides and its toxicological significance are presented. Methomyl metabolism in rats was investigated in detail as was Croneton in the rat, cow, pig and chicken. Carbaryl and carbofuran were admin...

  17. Insecticides and excitation behavior.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Treatment of mosquitoes with insecticides can result from exposure to surface contact or sprays. Efficacy of surface contact can be impacted by landing and resting behavior on treated surfaces. Behavioral analysis of the landing and resting responses of 3 different mosquito species to pyrethroid-t...

  18. ANTICHOLINESTERASE INSECTICIDE RETROSPECTIVE

    PubMed Central

    Casida, John E.; Durkin, Kathleen A.

    2012-01-01

    The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades. About 90 of these compounds are still in use – the largest number for any insecticide chemotype or mode of action. In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death. The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction. Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations. Species selectivity is determined in part by inhibitor and target site specificity. Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity. Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others. Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains. The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10 years ago for several reasons: there have been no major new compounds for 30 years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed. Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system. The OPs and MCs are down

  19. Global Trends in the Use of Insecticides to Control Vector-Borne Diseases

    PubMed Central

    van den Berg, Henk; Zaim, Morteza; Soares, Agnes; Ameneshewa, Birkinesh; Mnzava, Abraham; Hii, Jeffrey; Dash, Aditya Prasad; Ejov, Mikhail

    2012-01-01

    Background: Data on insecticide use for vector control are essential for guiding pesticide management systems on judicious and appropriate use, resistance management, and reduction of risks to human health and the environment. Objective: We studied the global use and trends of insecticide use for control of vector-borne diseases for the period 2000 through 2009. Methods: A survey was distributed to countries with vector control programs to request national data on vector control insecticide use, excluding the use of long-lasting insecticidal nets (LNs). Data were received from 125 countries, representing 97% of the human populations of 143 targeted countries. Results: The main disease targeted with insecticides was malaria, followed by dengue, leishmaniasis, and Chagas disease. The use of vector control insecticides was dominated by organochlorines [i.e., DDT (dichlorodiphenyltrichloroethane)] in terms of quantity applied (71% of total) and by pyrethroids in terms of the surface or area covered (81% of total). Global use of DDT for vector control, most of which was in India alone, was fairly constant during 2000 through 2009. In Africa, pyrethroid use increased in countries that also achieved high coverage for LNs, and DDT increased sharply until 2008 but dropped in 2009. Conclusions: The global use of DDT has not changed substantially since the Stockholm Convention went into effect. The dominance of pyrethroid use has major implications because of the spread of insecticide resistance with the potential to reduce the efficacy of LNs. Managing insecticide resistance should be coordinated between disease-specific programs and sectors of public health and agriculture within the context of an integrated vector management approach. PMID:22251458

  20. Evaluation of Olyset™ insecticide-treated nets distributed seven years previously in Tanzania

    PubMed Central

    Tami, Adriana; Mubyazi, Godfrey; Talbert, Alison; Mshinda, Hassan; Duchon, Stéphane; Lengeler, Christian

    2004-01-01

    Background Insecticide-treated nets represent currently a key malaria control strategy, but low insecticide re-treatment rates remain problematic. Olyset™ nets are currently one of two long-lasting insecticidal nets recommended by WHO. An assessment was carried out of the effect of Olyset™ nets after seven years of use in rural Tanzania. Methods A survey of Olyset™ nets was conducted in two Tanzanian villages to examine their insecticide dosage, bioassay efficacy and desirability compared with ordinary polyester nets. Results Of 103 randomly selected nets distributed in 1994 to 1995, 100 could be traced. Most nets were in a condition likely to offer protection against mosquito biting. Villagers appreciated mainly the durability of Olyset™ nets and insecticide persistence. People disliked the small size of these nets and the light blue colour and preferred a smaller mesh size, features that can easily be modified. At equal price, 51% said they would prefer to buy an Olyset™ net and 49% opted for an ordinary polyester net. The average permethrin content was 33%-41% of the initial insecticide dose of 20,000 mg/Kg. Bioassay results indicated high knock-down rates at 60 minutes, but the mosquito mortality after 24 hours was rather low (mean: 34%). No significant correlation was found between bioassay results and insecticide concentration in and on the net. Conclusions Olyset™ nets are popular, durable and with a much longer insecticide persistence than ordinary polyester nets. Hence, Olyset™ nets are one of the best choices for ITN programmes in rural malaria-endemic areas. PMID:15225349

  1. Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats.

    PubMed

    Visser, Sandra A G; Sällström, Björn; Forsberg, Tomas; Peletier, Lambertus A; Gabrielsson, Johan

    2006-04-01

    The aim of the present investigation was to develop a pharmacokinetic-pharmacodynamic model for the characterization of clomethiazole (CMZ)-induced hypothermia and the rapid development of long-lasting tolerance in rats while taking into account circadian rhythm in baseline and the influence of handling. CMZ-induced hypothermia and tolerance was measured using body temperature telemetry in male Sprague-Dawley rats, which were given s.c. bolus injections of 0, 15, 150, 300, and 600 micromol kg(-1) and 24-h s.c. continuous infusions of 0, 20, and 40 micromol kg(-1) h(-1) using osmotic pumps. The duration of tolerance was studied by repeated injections of 300 micromol kg(-1) at 3- to 32-day intervals. Plasma exposure to CMZ was obtained in satellite groups of catheterized rats. Fitted population concentration-time profiles served as input for the pharmacodynamic analysis. The asymmetric circadian rhythm in baseline body temperature was successfully described by a novel negative feedback model incorporating external light-dark conditions. An empirical function characterized the transient increase in temperature upon handling of the animal. A feedback model for temperature regulation and tolerance development allowed estimation of CMZ potency at 30 +/- 1 microM. The delay in onset of tolerance was estimated via a series of four transit compartments at 7.6 +/- 2 h. The long-lasting tolerance was assumed to be caused by inactivation of a mediator with an estimated turnover time of 46 +/- 3 days. This multicomponent turnover model was able to quantify the CMZ-induced hypothermia, circadian rhythm in baseline, and rapid onset of a long-lasting tolerance to CMZ in rats. PMID:16339393

  2. A novel red long lasting phosphorescent (LLP) material {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+}, Sm{sup 3+}

    SciTech Connect

    Wang Jing; Su Qiang . E-mail: cessuq@zsu.edu.cn; Wang Shubin

    2005-04-20

    A novel red long lasting phosphorescent materials {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+},Sm{sup 3+} is firstly synthesized by high-temperature solid-state reaction. The influence of Sm{sup 3+} ions on luminescence and long lasting phosphorescence properties of Mn{sup 2+} in phosphor {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+},Sm{sup 3+} are systematically investigated. It is found that the red phosphorescence ({lambda} = 616 nm) performance of Mn{sup 2+} ion such as brightness and duration is largely improved when Sm{sup 3+} ion is co-doped into the matrix in which Mn{sup 2+} ion acts as luminescent center and Sm{sup 3+} ion plays an important role of electron trap. Thermoluminescence spectrums show that there exists one peak in {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+},Sm{sup 3+}, the depth of which is 0.33 eV, and that there are three peaks in {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+}, among which the depth of the lowest temperature peak in {beta}-Zn{sub 3}(PO{sub 4}){sub 2}:Mn{sup 2+} is 0.37 eV. Such differences in the trap depth result in the improvement of red long lasting phosphorescence of Mn{sup 2+} in present matrix.

  3. Short stressor induced long-lasting increases of vasopressin stores in hypothalamic corticotropin-releasing hormone (CRH) neurons in adult rats.

    PubMed

    Schmidt, E D; Binnekade, R; Janszen, A W; Tilders, F J

    1996-09-01

    Recently, we demonstrated that single administration of interleukin-1 beta (IL-1) to adult rats induces a long-lasting (weeks) increase of vasopressin (AVP) stores in terminals of CRH neurons in the external zone of the median eminence (ZEME). This is accompanied by hypersecretion of AVP into the pituitary portal circulation and long-lasting hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis to stressors. Here, we determine whether this form of plasticity of hypothalamic CRH neurons is specific for IL-1 or represents a general response to a stressor. Single exposure of rats to lipopolysaccharide (LPS), IL-1, brain surgery or electric footshocks increases the AVP stores in the ZEME 7 and 11 days later. Exposure to insulin or ether does not affect the AVP stores. The stressors have little or no effect on the CRH stores in the ZEME. The amplitude of the increase in AVP as measured 7-11 days after stimulation correlates with the overall ACTH response to the stressor (area under curve, r = 0.89, P < 0.0001), with the peak ACTH levels (r = 0.52, P < 0.05), but not with the duration of the ACTH response nor with any parameter of the corticosterone response. Administration of ACTH or corticosterone at doses that mimic stress-induced plasma levels does not increase AVP stores 7 days later. We conclude that long-lasting increases of AVP stores in CRH terminals in the ZEME can be induced by various stressors and postulate that the amplitude of such increases depends on the degree of activation of the CRH neurons by the stressor. (NWO grant: 900-543-101.) PMID:8877819

  4. Genome-wide RNA profiling of long-lasting stem cell-like memory CD8 T cells induced by Yellow Fever vaccination in humans.

    PubMed

    Fuertes Marraco, Silvia A; Soneson, Charlotte; Delorenzi, Mauro; Speiser, Daniel E

    2015-09-01

    The live-attenuated Yellow Fever (YF) vaccine YF-17D induces a broad and polyfunctional CD8 T cell response in humans. Recently, we identified a population of stem cell-like memory CD8 T cells induced by YF-17D that persists at stable frequency for at least 25 years after vaccination. The YF-17D is thus a model system of human CD8 T cell biology that furthermore allows to track and study long-lasting and antigen-specific human memory CD8 T cells. Here, we describe in detail the sample characteristics and preparation of a microarray dataset acquired for genome-wide gene expression profiling of long-lasting YF-specific stem cell-like memory CD8 T cells, compared to the reference CD8 T cell differentiation subsets from total CD8 T cells. We also describe the quality controls, annotations and exploratory analyses of the dataset. The microarray data is available from the Gene Expression Omnibus (GEO) public repository with accession number GSE65804. PMID:26484272

  5. Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus.

    PubMed

    Gouveia, Telma Luciana Furtado; Scorza, Fulvio Alexandre; Silva, Michele Juliana Vieira; Bandeira, Tatiane de Aquino; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, Marcelo de Paula; Araujo, Thiago Rodrigues; Frangiotti, Maria Isabel Berzaghi; Amado, Débora; Cavalheiro, Esper Abrão; Silva, José Antonio; Naffah-Mazzacoratti, Maria da Graça

    2011-01-01

    Statins may act on inflammatory responses, decreasing oxidative stress and also reducing temperature after a brain ischemic insult. Previous data have indicated that statins protect neurons from death during long-lasting status epilepticus (SE) and attenuate seizure behaviors in animals treated with kainic acid. In this context, the study described here aimed to investigate the effect of lovastatin on body temperature and on mRNA expression levels of hippocampal cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 and B2 receptors of rats submitted to pilocarpine-induced SE. Quantitative real-time polymerase chain reaction showed a significant decrease in mRNA expression of interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 receptor in animals with SE treated with lovastatin, compared with untreated animals with SE (P<0.001). Lovastatin also reduced SE-induced hyperthermia, indicating that mechanisms related to brain protection are triggered by this drug under conditions associated with acute excitotoxicity or long-lasting SE. PMID:21130693

  6. Inability to evoke a long-lasting protective immune response to respiratory syncytial virus infection in mice correlates with ineffective nasal antibody responses.

    PubMed

    Singleton, Richard; Etchart, Nathalie; Hou, Sam; Hyland, Lisa

    2003-11-01

    Long-lasting protective antibody is not normally generated in children following primary respiratory syncytial virus (RSV) infection, frequently leading to reinfection. We used the BALB/c mouse model to examine the role of the nasal-associated lymphoid tissue and the bone marrow in the generation of RSV-specific long-lasting plasma cells, with a view to further understanding the mechanisms responsible for the poorly sustained RSV antibody levels following primary infection. We show here that substantial numbers of RSV-specific plasma cells were generated in the bone marrow following challenge, which were maintained thereafter. In contrast, in the nasal-associated lymphoid tissue, RSV-specific plasma cell numbers waned quickly both after primary infection and after challenge and were not maintained at a higher level after boosting. These data indicate that the inability to generate a robust local mucosal response in the nasal tissues may contribute substantially to the likelihood of subsequent reinfection and that the presence of serum anti-RSV antibody without local protection is not enough to protect against reinfection. PMID:14557616

  7. Characterization of Long-Lasting Oatp Inhibition by Typical Inhibitor Cyclosporine A and In Vitro-In Vivo Discrepancy in Its Drug Interaction Potential in Rats.

    PubMed

    Taguchi, Takayuki; Masuo, Yusuke; Kogi, Tatsuya; Nakamichi, Noritaka; Kato, Yukio

    2016-07-01

    Quantitative assessment of potential drug-drug interactions (DDIs) is one of the major focuses in drug development. The aim of the present study was to quantitatively evaluate in vitro-in vivo discrepancy of DDI potential for prototypical organic anion transporting polypeptide (Oatp) inhibitor cyclosporine A (CsA) using rats. Plasma concentration of pravastatin, prototypical Oatp substrate, after oral administration was increased by CsA intravenously administered at 1 d before the pravastatin administration. The ratio of the area under the curve of pravastatin to the control was much higher than the R-values calculated using the plasma unbound concentrations of CsA and the inhibition constant (Ki) assessed in isolated hepatocytes, indicating in vitro-in vivo discrepancy. This interaction with pravastatin persisted for 3 d after CsA administration, demonstrating long-lasting inhibition in vivo. The Ki value for unbound CsA in the presence of serum was comparable with that in its absence. M1, the major metabolite of CsA inhibited pravastatin uptake at much higher concentration compared with its plasma unbound concentration. Thus, the DDI potential of CsA-mediated hepatic Oatp inhibition cannot be extrapolated from in vitro data, and this could be due to the long-lasting Oatp inhibition by CsA, but not the effect of plasma protein or metabolites. PMID:27290622

  8. Acute and long-lasting effects of peripheral injection of caerulein and CCK-8 on the central GABAergic system in mice.

    PubMed

    Nagahama, H

    1989-01-01

    Acute and long-lasting effects of peripheral injection of caerulein (CLN) and cholecystokinin octapeptide (CCK-8) on the gamma-aminobutylic acid (GABA) content and the GABA accumulation by aminooxyacetic acid (AOAA) in the discrete brain regions of mice were examined. The content and accumulation of GABA in the striatum, hypothalamus, and frontal cortex was measured with high performance liquid chromatography with electrochemical detection (HPLC-ECD). The GABA content slightly decreased in the striatum 60 min after CLN and CCK-8 were administered, whereas it slightly increased in the hypothalamus and frontal cortex. Moreover, with CLN and CCK-8, the GABA accumulation after AOAA treatment decreased in the striatum and hypothalamus 30 min after injection. Meanwhile, when administering CLN, the GABA content as well as the GABA accumulation after AOAA treatment increased in the striatum and frontal cortex 1 day after injection, and continued to increase the second and third day in the striatum. These results showed that peripheral injection of CLN and CCK-8 had effects on the central GABAergic system with local specific actions, and also the long-lasting and time-dependent biphasic effects of CLN. PMID:2622803

  9. Delayed mortality effects cut the malaria transmission potential of insecticide-resistant mosquitoes.

    PubMed

    Viana, Mafalda; Hughes, Angela; Matthiopoulos, Jason; Ranson, Hilary; Ferguson, Heather M

    2016-08-01

    Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60-100% and 3-61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance. PMID:27402740

  10. Reduction of epileptiform activity by valproic acid in a mouse model of Alzheimer's disease is not long-lasting after treatment discontinuation.

    PubMed

    Ziyatdinova, Sofya; Viswanathan, Jayashree; Hiltunen, Mikko; Tanila, Heikki; Pitkänen, Asla

    2015-05-01

    Patients with Alzheimer's disease are at increased risk for unprovoked seizures and epilepsy compared with age-matched controls. Experimental evidence suggests that neuronal hyperexcitability and epilepsy can be triggered by amyloid-β (Aβ), the main component of amyloid plaques. Previous studies demonstrated that the administration of an anticonvulsant and histone deacetylase inhibitor, valproic acid, leads to a long-lasting reduction in Aβ levels. Here we used an APdE9 mouse model of Alzheimer's disease with overproduction of Aβ to assess whether treatment with valproic acid initiated immediately after epilepsy onset modifies the occurrence of epileptiform activity. We also analyzed whether the effect is long-lasting and associated with antiamyloidogenesis and histone-modifications. Male APdE9 mice (15 week old) received daily intraperitoneal injections of 30mg/kg valproic acid for 1 week. After a 3-week wash-out, the same animals received injections of a higher dose of valproic acid (300mg/kg) daily for 1 week. Long-term video-electroencephalography monitoring was performed prior to, during, and after the treatments. Aβ and total histone H3 and H4 acetylation levels were measured at 1 month after the final valproic acid treatment. While 30mg/kg valproic acid reduced spontaneous seizures in APdE9 mice (p<0.05, chi-square), epileptiform discharges were not reduced. Administration of 300mg/kg valproic acid, however, reduced epileptiform discharges in APdE9 mice for at least 1 week after treatment discontinuation (p<0.05, Wilcoxon test), but there was no consistent long-term effects on epileptiform activity after treatment withdrawal. Further, we found no long-lasting effect on Aβ levels (p>0.05, Mann-Whitney test), only a meager increase in global acetylation of histone H3 (p<0.05), and no effects on H4 acetylation (p>0.05). In conclusion, valproic acid treatment of APdE9 mice at the stage when amyloid plaques are beginning to develop and epileptiform activity

  11. Best practices for an insecticide-treated bed net distribution programme in sub-Saharan eastern Africa

    PubMed Central

    2011-01-01

    Insecticide-treated bed nets are the preeminent malaria control means; though there is no consensus as to a best practice for large-scale insecticide-treated bed net distribution. In order to determine the paramount distribution method, this review assessed literature on recent insecticide treated bed net distribution programmes throughout sub-Saharan Eastern Africa. Inclusion criteria were that the study had taken place in sub-Saharan Eastern Africa, targeted malaria prevention and control, and occurred between 1996 and 2007. Forty-two studies were identified and reviewed. The results indicate that distribution frameworks varied greatly; and consequently so did outcomes of insecticide-treated bed net use. Studies revealed consistent inequities between urban and rural populations; which were most effectively alleviated through a free insecticide-treated bed net delivery and distribution framework. However, cost sharing through subsidies was shown to increase programme sustainability, which may lead to more long-term coverage. Thus, distribution should employ a catch up/keep up programme strategy. The catch-up programme rapidly scales up coverage, while the keep-up programme maintains coverage levels. Future directions for malaria should include progress toward distribution of long-lasting insecticide-treated nets. PMID:21651815

  12. Teppeki, selective insecticide about Bombus terrestris.

    PubMed

    Fanigliulo, Angela; Filì, Vittorio; Pacella, Rosa; Comes, Soccorsa; Crescenzi, Aniello

    2009-01-01

    At a time when a highly controversial debate about the causes of the widespread deaths of bees is taking place all over Europe, which accused the agriculture and its practices with particular reference to the harmful effects of some insecticides, it seems important to point out as another insecticide, the Teppeki, can be selective about bumble and have a good compatibility with the activity of the apiaries. This insecticide has the active ingredient flonicamid (500 g/kg) belonging to a new chemical class, called pyridinecarboxamides: the product works systemic and is known as having a long lasting efficacy against all important aphid species. Bioagritest test facility of Pignola (PZ, Italy) has conducted in two successive production cycles an experimental trial on a tomato hydroponic cultivation within the Agricola Bonsai farm in Sibari (CS, Italy), whose objective was to measure the selectivity of flonicamid on Bombus terrestris, insects playing an important role in the pollination of certain species grown in greenhouse such as Tomato, Eggplant, Pepper and Cucumber. On the pollinated flower B. terrestris leaves some trace of its visit, a typical dark trademark: on the detection of the marking of flowers was based the testing program conducted by Bioagritest. Two thesis were compared: A, standard) treatment with a foliar insecticide, the neonicotinoide acetamiprid, normally used for control of aphids and whiteflies (unlike other neonicotinoides--imidacloprid and thiametoxam--quite selective about B. terrestris) and B, Teppeki) foliar treatment with Teppeki, to the maximum dose indicated on the label. The experimental design included the use of randomized blocks with 4 repetitions (4 plots/thesis with 100 plants each). In every thesis six B. terrestris hives were placed 2 days before treatment: the respective holes remained closed during the treatment and the 12 following hours. In order to verify the pollination, by the detection of the flower marking, 2 flowers

  13. A LIGHT-CURVE MODEL OF THE SYMBIOTIC NOVA PU Vul (1979): A VERY QUIET EXPLOSION WITH LONG-LASTING FLAT PEAK

    SciTech Connect

    Kato, Mariko; Hachisu, Izumi; Cassatella, Angelo; Gonzalez-Riestra, Rosario

    2011-02-01

    We present a light-curve model of the symbiotic nova PU Vul (Nova Vulpeculae 1979) that shows a long-lasting flat peak with no spectral indication of wind mass loss before decline. Our quasi-evolution models consisting of a series of static solutions explain both the optical flat peak and ultraviolet (UV) light curve simultaneously. The white dwarf mass is estimated to be {approx}0.6 M{sub sun}. We also provide a new determination of the reddening, E(B - V) = 0.43 {+-} 0.05, from UV spectral analysis. Theoretical light-curve fitting of UV 1455 A provides the distance of d = 3.8 {+-} 0.7 kpc.

  14. GRB 120711A: an intense INTEGRAL burst with long-lasting soft γ-ray emission and a powerful optical flash

    NASA Astrophysics Data System (ADS)

    Martin-Carrillo, A.; Hanlon, L.; Topinka, M.; LaCluyzé, A. P.; Savchenko, V.; Kann, D. A.; Trotter, A. S.; Covino, S.; Krühler, T.; Greiner, J.; McGlynn, S.; Murphy, D.; Tisdall, P.; Meehan, S.; Wade, C.; McBreen, B.; Reichart, D. E.; Fugazza, D.; Haislip, J. B.; Rossi, A.; Schady, P.; Elliott, J.; Klose, S.

    2014-07-01

    A long and intense γ-ray burst (GRB) was detected by INTEGRAL on 11 July 2012 with a duration of ~115 s and fluence of 2.8 × 10-4 erg cm-2 in the 20 keV-8 MeV energy range. GRB 120711A was at z ~ 1.405 and produced soft γ-ray emission (>20 keV) for at least ~10 ks after the trigger. The GRB was observed by several ground-based telescopes that detected a powerful optical flash peaking at an R-band brightness of ~11.5 mag at ~126 s after the trigger, or ~9th magnitude when corrected for the host galaxy extinction (AV ~ 0.85). The X-ray afterglow was monitored by the Swift, XMM-Newton, and Chandra observatories from 8 ks to 7 Ms and provides evidence for a jet break at ~0.9 Ms. We present a comprehensive temporal and spectral analysis of the long-lasting soft γ-ray emission detected in the 20-200 keV band with INTEGRAL/IBIS, the Fermi/LAT post-GRB detection above 100 MeV, the soft X-ray afterglow and the optical/near-infrared detections from Watcher, Skynet/PROMPT, GROND, and REM. The prompt emission had a very hard spectrum (Epeak ~ 1 MeV) and yields an Eγ,iso ~ 1054 erg (1 keV-10 MeV rest frame), making GRB 120711A one of the most energetic GRBs detected so far. We modelled the long-lasting soft γ-ray emission using the standard afterglow scenario, which indicates a forward shock origin. The combination of data extending from the near-infrared to GeV energies suggest that the emission is produced by a broken power-law spectrum consistent with synchrotron radiation. The afterglow is well modelled using a stratified wind-like environment with a density profile k ~ 1.2, suggesting a massive star progenitor (i.e. Wolf-Rayet) with a mass-loss rate between ~10-5-10-6 M⊙ yr-1 depending on the value of the radiative efficiency (ηγ = 0.2 or 0.5). The analysis of the reverse and forward shock emission reveals an initial Lorentz factor of ~120-340, a jet half-opening angle of ~2°-5°, and a baryon load of ~10-5 - 10-6 M⊙ consistent with the expectations of the

  15. Observation of the simultaneous transport of Asian mineral dust aerosols with anthropogenic pollutants using a POPC during a long-lasting dust event in late spring 2014

    NASA Astrophysics Data System (ADS)

    Pan, Xiaole; Uno, Itsushi; Hara, Yukari; Kuribayashi, Masatoshi; Kobayashi, Hiroshi; Sugimoto, Nobuo; Yamamoto, Shigekazu; Shimohara, Takaaki; Wang, Zifa

    2015-03-01

    We observed a long-lasting dust event from 25 May to 2 June 2014, using a polarization optical particle counter (POPC). The transport of dust plumes over East Asia was verified on the basis of observations of Moderate Resolution Imaging Spectroradiometer, a lidar network, and surface synoptic observation stations. Mixing of dust and anthropogenic pollutants was investigated according to the variation in the depolarization ratio as a function of particle size. The nonsphericity of dust particles varied due to the impact of anthropogenic pollutants on their pathway. In the coarse mode, dust particles always had a clear nonspherical configuration, although large amounts of nitrate were also present. Supermicron particles are occasionally present in a spherical configuration, possibly due to the complex mixing of natural dust and anthropogenic particles. Statistically, ~64% of the total nitrate mass was deemed to be transported from outside of Japan due to a trapping effect in the dust plume.

  16. [Animal experimental evidence of the long-lasting efficacy of etofenamate by prolongation of the half-life after intramuscular application].

    PubMed

    Dell, H D; Brons, J; Fiedler, J; Kamp, R; Pelster, B

    1990-03-01

    Animal Experimental Evidence of Long-lasting Liberation of Etofenamate by Half-life Prolongation after Intramuscular Application. The purpose of this investigation was to show in animal experiments that by i.m. injection of etofenamate (active substance of Rheumon i.m.) in oily solution the following effects could be obtained: a fast onset of action (gain of therapeutically relevant drug levels shortly after injection) a long-lasting efficacy (prolonged liberation from the oil depot) and better tolerability as compared to other intramuscularly applicable antiinflammatory drugs (avoidance of high plasma spikes). Etofenamate in rats is liberated with a half-life of 1.29 days from the place of application (cutaneous half-life 8.5 h). Flufenamic acid in muscles is found only in traces. After i.m. administration of etofenamate to dogs maximum plasma levels of etofenamate and flufenamic acid were reached within 2 and 4 h, resp. The mean half-lives of plasma elimination are 14 h for etofenamate and 23.2 h for flufenamic acid formed esterolytically from etofenamate (flufenamic acid oral half-life 2-4 h). Maximum plasma levels after etofenamate are only 6.5-11.8% of the maximum levels after equivalent amounts of flufenamic acid administered orally. According to these data etofenamate i.m. is a drug formulation with fast increasing plasma levels, prolonged half-life and lower maximum plasma levels as compared to orally administered preparations. The results are confirmed in animals (pharmacodynamics, toxicology and tolerability) and man (kinetics, clinical studies). PMID:2346540

  17. Activation of glial glutamate transporter via MAPK p38 prevents enhanced and long-lasting non-evoked resting pain after surgical incision in rats.

    PubMed

    Reichl, Sylvia; Segelcke, Daniel; Keller, Viktor; Jonas, Robin; Boecker, Armin; Wenk, Manuel; Evers, Dagmar; Zahn, Peter K; Pogatzki-Zahn, Esther M

    2016-06-01

    Pain after surgery has recently become a major issue not only due to lack of treatment success in the acute phase; even more alarming is the large number of patients developing prolonged pain after surgery. Because spinal glutamate as well as spinal glia plays a major role in acute incisional pain, we investigated the role of the spinal glial glutamate transporters (GT), GLAST, GLT-1, for acute and prolonged pain and hyperalgesia caused by an incision. Spinal administration of the GT-inhibitor DL-TBOA increased non-evoked pain but not evoked pain behavior (hyperalgesia) up to 2 weeks after incision. In accordance, spinal GLAST (and to a lesser degree GLT-1) were upregulated after incision for several days. Long-term incision induced GT upregulation was prevented by long-lasting p38-inhibitor administration but not by long-lasting ERK1/2-inhibition after incision. In accordance, daily treatment with the p38-inhibitor (but not the ERK1/2 inhibitor) prolonged non-evoked but not evoked pain behavior after incision. In electrophysiological experiments, spontaneous activity of high threshold (HT) (but not wide dynamic range (WDR)) neurons known to transmit incision induced non-evoked pain was increased after prolonged treatment with the p38-inhibitor. In conclusion, our findings indicate a new spinal pathway by which non-evoked pain behavior after incision is modulated. The pathway is modality (non-evoked pain) and neuron (HT) specific and disturbance contributes to prolonged long-term pain after surgical incision. This may have therapeutic implications for the treatment of acute and - even more relevant - for prevention of chronic pain after surgery in patients. PMID:26920805

  18. Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

    SciTech Connect

    Axelstad, Marta Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Soren Peter; Hougaard, Karin Sorig; Hass, Ulla

    2008-10-01

    Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T{sub 4}) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T{sub 4} during development. This supports the hypothesis that decreased T{sub 4} may be a relevant predictor for long-lasting developmental neurotoxicity.

  19. Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

    PubMed

    Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; Hass, Ulla

    2008-10-01

    Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity. PMID:18573268

  20. MHC class II tetramer analyses in AE37-vaccinated prostate cancer patients reveal vaccine-specific polyfunctional and long-lasting CD4(+) T-cells.

    PubMed

    Anastasopoulou, Eleftheria A; Voutsas, Ioannis F; Papamichail, Michael; Baxevanis, Constantin N; Perez, Sonia A

    2016-07-01

    Realizing the basis for generating long-lasting clinical responses in cancer patients after therapeutic vaccinations provides the means to further ameliorate clinical efficacy. Peptide cancer vaccines stimulating CD4(+) T helper cells are often promising for inducing immunological memory and persistent CD8(+) cytotoxic T cell responses. Recent reports from our clinical trial with the AE37 vaccine, which is a HER2 hybrid polypeptide, documented its efficacy to induce CD4(+) T cell immunity, which was associated with clinical improvements preferentially among HLA-DRB1*11(+) prostate cancer patients. Here, we performed in-depth investigation of the CD4(+) T cell response against the AE37 vaccine. We used the DR11/AE37 tetramer in combination with multicolor flow cytometry to identify and characterize AE37-specific CD4(+) T cells regarding memory and Tregs phenotype in HLA-DRB1*11(+) vaccinated patients. To verify vaccine-specific immunological memory in vivo, we also assessed AE37-specific CD4(+) T cells in defined CD4(+) memory subsets by cell sorting. Finally, vaccine-induced AE37-specific CD4(+) T cells were assessed regarding their functional profile. AE37-specific memory CD4(+) T cells could be detected in peptide-stimulated cultures from prostate cancer patients following vaccination even 4 y post-vaccination. The vast majority of vaccine-induced AE37-specific CD4(+) T cells exhibited a multifunctional, mostly Th1 cytokine signature, with the potential of granzyme B production. In contrast, we found relatively low frequencies of Tregs among AE37-specific CD4(+) T cells. This is the first report on the identification of vaccine-induced HER2-specific multifunctional long-lasting CD4(+) T cells in vaccinated prostate cancer patients. PMID:27622033

  1. Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

    PubMed Central

    Cupertino, Marli C; Costa, Kyvia L C; Santos, Daiane C M; Novaes, Rômulo D; Condessa, Suellen S; Neves, Ana C; Oliveira, Juraci A; Matta, Sérgio L P

    2013-01-01

    Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis. PMID:24020407

  2. Exposure of mice to secondhand smoke elicits both transient and long-lasting transcriptional changes in cancer-related functional networks.

    PubMed

    Tommasi, Stella; Zheng, Albert; Besaratinia, Ahmad

    2015-05-15

    Secondhand smoke (SHS) has long been linked to lung cancer and other diseases in nonsmokers. Yet, the underlying mechanisms of SHS carcinogenicity in nonsmokers remain to be elucidated. We investigated the immediate and long-lasting effects of SHS exposure on gene expression in mice in vivo. We exposed mice whole body to SHS for 5 h/day, 5 days/week for 4 months in exposure chambers of a microprocessor-controlled smoking machine. Subsequently, we performed microarray gene expression profiling, genome-wide, to construct the pulmonary transcriptome of SHS-exposed mice, immediately after discontinuation of exposure (T0) and following 1-month (T1) and 7-month (T2) recoveries in clean air. Sub-chronic exposure of mice to SHS elicited a robust transcriptomic response, including both reversible and irreversible changes in gene expression. There were 674 differentially expressed transcripts immediately after treatment (T0), of which the majority were involved in xenobiotic metabolism, signaling, and innate immune response. Reduced, yet, substantial numbers of differentially expressed transcripts were detectable in mice after cessation of SHS-exposure (254 transcripts at T1 and 30 transcripts at T2). Top biofunctional networks disrupted in SHS-exposed mice, even after termination of exposure, were implicated in cancer, respiratory disease, and inflammatory disease. Our data show that exposure of mice to SHS induces both transient and long-lasting changes in gene expression, which impact cancer-related functional networks. The pattern of transcriptional changes in SHS-exposed mice may provide clues on the underlying mechanisms of lung tumorigenesis in nonsmokers. Our findings underscore the importance of eliminating SHS from environments where nonsmokers are unavoidably exposed to this carcinogen. PMID:25346222

  3. The valence of the long-lasting emotional experiences with various handlers modulates discrimination and generalization of individual humans in sheep.

    PubMed

    Destrez, A; Coulon, M; Deiss, V; Delval, E; Boissy, A; Boivin, X

    2013-11-01

    Between-farm variation in animal reactions to humans can reflect different management styles and behavioral tendencies among farmers. Animals are well known to discriminate among humans, but less clear is the key issue of whether they more or less easily generalize their experience from specific humans to others depending on management style. Here, we chose 2 contrasted management styles by known handlers: "gentle" management, that is, long-lasting exposure to positive human interactions (with limited negative interactions), and "aversive" management including long-lasting exposure to various negative human interactions (with only food delivery considered a positive interaction) and aversive events. Over a period of 19 wk, 15 female lambs were exposed to the gentle management treatment ("gently treated" group) and another 15 lambs ("aversively treated" group) were exposed to the aversive management treatment. To facilitate discrimination by animals, experimenters wore white clothes for aversive events and green clothes for farming handling (positive handling and feeding for the gently treated group and only feeding for the aversively treated group). Sheep perception of the human was assessed after the management period by submitting lambs from each group to 2 standardized tests: 1) the presence of a stationary human (familiar human in white vs. familiar human in green vs. unknown human) and 2) the presence of a moving human (familiar human in white vs. familiar human in green vs. unknown human). As expected, during the stationary human test, aversively treated lambs spent less time in the human zone (P<0.0001), showed greater latency to approach the human (P=0.05), and had fewer contacts with the human (P=0.05) than gently treated lambs. During the moving human test, aversively treated lambs also showed a greater escape distance from humans than gently treated lambs (P<0.0001). Aversively treated lambs showed the same fear responses towards familiar and unknown

  4. A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity.

    PubMed Central

    Baker-Zander, S.; Sell, S.

    1980-01-01

    Inoculation of the causative agent of syphilis, Treponema pallidum into the testes of rabbits initiated the following sequence of events: 1) a rapid proliferation of organisms in the interstitial tissues of the testes, reaching a maximum at about 10-11 days after infection; 2) systemic spread of organisms primarily in the lymphoid organs; 3) a prompt immune response manifested by hyperplasia of T cell domains in draining lymph nodes and spleen, blast transformation responses of lymphoid cells to sonicates of T pallidum, the appearance of serum antibody, and the marked infiltration of the infected areas of the testes by T cells; 4) essential clearing of organisms identified by immunofluorescence from the infected site 10-14 days after infection associated with evolution of the inflammatory response from primarily a T cell infiltrate to a larger mononuclear cell type, and the immunofluorescent identification of presumptive T pallidum antigen in macrophages; 5) interstitial fibrosis or resolution 17-21 days after infection so that examination of infected testes from 1 to 24 months later reveals foci of tubular atrophy and fibrosis of varying size, alternating with regenerated tubules, separated by interstitial areas with only minimal fibrosis. During the long period of latency there is no evidence of atrophy or hypoplasia of the lymphoid organs and long-lasting T cell memory with regard to T pallidum sonicates is demonstrable. Reinfection of previously inoculated rabbits indicates partial protection at 25 days after infection followed by essentially complete protection after 55 days. It is concluded that there is a prompt and long-lasting immune response to T pallidum in experimentally infected rabbits. The main mechanism for destruction of infecting organisms appears to be T-cell-initiated macrophage-mediated destruction, but a role for antibody dependent phagocytosis cannot be ruled out. The reason that some organisms may survive in various body organs remains

  5. A renaissance for botanical insecticides?

    PubMed

    Isman, Murray B

    2015-12-01

    Botanical insecticides continue to be a subject of keen interest among the international research community, reflected in the steady growth in scientific publications devoted to the subject. Until very recently though, the translation of that theory to practice, i.e. the commercialisation and adoption of new botanical insecticides in the marketplace, has seriously lagged behind. Strict regulatory regimes, long the bane of small pesticide producers, are beginning to relax some of the data requirements for 'low-risk' pesticide products, facilitating movement of more botanicals into the commercial arena. In this paper I discuss some of the jurisdictions where botanicals are increasingly finding favour, some of the newer botanical insecticides in the plant and animal health arsenal and some of the specific sectors where botanicals are most likely to compete effectively with other types of insecticidal product. PMID:26251334

  6. A long-lasting taxonomic problem in European Sympycnus resolved, with the description of a new species and data on habitat preferences.

    PubMed

    Pollet, Marc; Persson, Magnus; Bøggild, Esben; Crossley, Roy

    2015-01-01

    Type specimens of Sympycnus pulicarius, S. annulipes, S. cinerellus and S. desoutteri were examined to clear up a long-lasting taxonomic confusion. Our study revealed that they represent, together with S. pygmaeus and S. annulipes var. brunnitibialis, a single species, with S. pulicarius as the senior subjective synonym, which is redescribed in this paper. Lectotypes were designated for Dolichopus pulicarius, Porphyrops annulipes, Chrysotus cinerellus and Sympycnus desoutteri. The postpedicel in this species shows substantial variation in shape and size, but the presence of a posteroventral bristle on the mid tibia is more reliable and the particular chaetotaxy and relative lengths of the tarsomeres of the male hind tarsus are entirely consistent. Both latter features separate S. pulicarius from another species, S. septentrionalis sp. nov., that is described here. Ecological data on both species were examined. An analysis of Malaise trap and white pan trap samples collected in Belgium revealed that S. pulicarius is most common in the western part of Flanders, and most abundant in open grassy habitats. In contrast to S. pulicarius, which is widespread over Europe, S. septentrionalis sp. nov. seems confined to northern Europe, where it exhibits a similar habitat preference. PMID:26624340

  7. Long-Lasting Phosphorescent Properties of Tb3+ Doped ZnO-P2O5-SiO2 Glasses

    NASA Astrophysics Data System (ADS)

    Cao, Yuxia

    2016-03-01

    The long-lasting phosphorescent glass with the composition of ZnO-P2O5-SiO2: Tb3+ was prepared by melt-quenched method. After irradiation by 254 nm light, a visible greenish light can be observed with the naked eyes, in the dark for up to 9 h after removal of the activating light. The luminescent properties of ZnO-P2O5-SiO2: Tb3+ were studied by fluorescence spectra, afterglow spectra and thermoluminescence spectra. The results show that the luminescent properties of the glasses become better with the increase of ZnO contents. The luminescent properties of glasses increase with the increase of Tb3+ contents. When 2% of ZnO is replaced by 2% of RO (RO=CaO, SrO, BaO), the luminescent property of glasses become worse in the order of CaO, SrO, BaO. The higher the contents of RO (RO=CaO, SrO, BaO) are, the worse the luminescent properties of the glasses become.

  8. N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits.

    PubMed

    Bouter, Yvonne; Dietrich, Katharina; Wittnam, Jessica L; Rezaei-Ghaleh, Nasrollah; Pillot, Thierry; Papot-Couturier, Sophie; Lefebvre, Thomas; Sprenger, Frederick; Wirths, Oliver; Zweckstetter, Markus; Bayer, Thomas A

    2013-08-01

    N-truncated Aβ4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ4-42 is as toxic as pyroglutamate Aβ3-42 and Aβ1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ4-42, pyroglutamate Aβ3-42 and Aβ1-42. Transgenic mice expressing Aβ4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction. PMID:23685882

  9. Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity

    NASA Astrophysics Data System (ADS)

    Dranoff, Glenn; Jaffee, Elizabeth; Lazenby, Audrey; Golumbek, Paul; Levitsky, Hyam; Brose, Katja; Jackson, Valerie; Hamada, Hirofumi; Pardoll, Drew; Mulligan, Richard C.

    1993-04-01

    To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4^+ and CD8^+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

  10. Long-lasting and bioactive hyaluronic acid-hydroxyapatite composite hydrogels for injectable dermal fillers: Physical properties and in vivo durability.

    PubMed

    Jeong, Seol-Ha; Fan, Ying-Fang; Baek, Jae-Uk; Song, Juha; Choi, Tae-Hyun; Kim, Suk-Wha; Kim, Hyoun-Ee

    2016-09-01

    Hyaluronic acid (HAc)-hydroxyapatite (HAp) composite hydrogels were developed to improve the biostability and bioactivity of HAc for dermal filler applications. Two kinds of HAc-HAp composite fillers were generated: HAcmicroHAp and HAc-nanoHAp composites. HAc-microHAp was fabricated by mixing HAp microspheres with HAc hydrogels, and HAc-nanoHAp was made by in situ precipitation of nano-sized HAp particles in HAc hydrogels. Emphasis was placed on the effect of HAp on the durability and bioactivity of the fillers. Compared with the pure HAc filler, all of the HAc-HAp composite fillers exhibited significant improvements in volumetric maintenance based on in vivo tests owing to their reduced water content and higher degree of biointegration between the filler and surrounding tissues. HAc-HAp composite fillers also showed noticeable enhancement in dermis recovery, promoting collagen and elastic fiber formation. Based on their long-lasting durability and bioactivity, HAc-HAp composite fillers have great potential for soft tissue augmentation with multifunctionality. PMID:27164868

  11. Behavioral and Movement Disorders due to Long-Lasting Myoclonic Status Epilepticus Misdiagnosed as ADHD in a Patient With Juvenile Myoclonic Epilepsy: Electroclinical Findings and Related Hemodynamic Changes.

    PubMed

    Fanella, Martina; Carnì, Marco; Morano, Alessandra; Albini, Mariarita; Lapenta, Leonardo; Casciato, Sara; Fattouch, Jinane; Di Castro, Elisabetta; Colonnese, Claudio; Vaudano, Anna Elisabetta; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2016-01-01

    Epilepsy and attention-deficit/hyperactivity disorder (ADHD) likely share common underlying neural mechanisms, as often suggested by both the evidence of electroencephalography (EEG) abnormalities in ADHD patients without epilepsy and the coexistence of these 2 conditions. The differential diagnosis between epilepsy and ADHD may consequently be challenging. In this report, we describe a patient presenting with a clinical association of "tics" and behavioral disorders that appeared 6 months before our first observation and had previously been interpreted as ADHD. A video-EEG evaluation documented an electroclinical pattern of myoclonic status epilepticus. On the basis of the revised clinical data, the EEG findings, the good response to valproate, the long-lasting myoclonic status epilepticus, and the enduring epileptic abnormalities likely causing behavioral disturbances, the patient's symptoms were interpreted as being the expression of untreated juvenile myoclonic epilepsy. The EEG-functional magnetic resonance imaging study revealed, during clinical generalized spike-and-wave and polyspike-and-wave discharges, positive blood oxygen level-dependent (BOLD) signal changes bilaterally in the thalamus, the prefrontal cortex (Brodmann area 6, supplementary motor area) and the cerebellum, and negative BOLD signal changes in the regions of the default mode network. Such findings, which are typical of BOLD changes observed in idiopathic generalized epilepsy, may also shed light on the anatomofunctional network underlying ADHD. PMID:25733678

  12. Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver

    PubMed Central

    2011-01-01

    Background The induction of sterile immunity and long lasting protection against malaria has been effectively achieved by immunization with sporozoites attenuated by gamma-irradiation or through deletion of genes. For mice immunized with radiation attenuated sporozoites (RAS) it has been shown that intrahepatic effector memory CD8+ T cells are critical for protection. Recent studies have shown that immunization with genetically attenuated parasites (GAP) in mice is also conferred by liver effector memory CD8+ T cells. Findings In this study we analysed effector memory cell responses after immunization of GAP that lack the P52 protein. We demonstrate that immunization with p52-GAP sporozoites also results in a strong increase of effector memory CD8+ T cells, even 6 months after immunization, whereas no specific CD4+ effector T cells response could be detected. In addition, we show that the increase of effector memory CD8+ T cells is specific for the liver and not for the spleen or lymph nodes. Conclusions These results indicate that immunization of mice with P. berghei p52-GAP results in immune responses that are comparable to those induced by RAS or GAP lacking expression of UIS3 or UIS4, with an important role implicated for intrahepatic effector memory CD8+ T cells. The knowledge of the mediators of protective immunity after immunization with different GAP is important for the further development of vaccines consisting of genetically attenuated sporozoites. PMID:22004696

  13. Training Lymnaea in the presence of a predator scent results in a long-lasting ability to form enhanced long-term memory.

    PubMed

    Forest, Jeremy; Sunada, Hiroshi; Dodd, Shawn; Lukowiak, Ken

    2016-06-01

    Lymnaea exposed to crayfish effluent (CE) gain an enhanced ability to form long-term memory (LTM). We test the hypothesis that a single CE exposure and operant conditioning training leads to long lasting changes in the capability of snails to form LTM when tested in pond water four weeks later. We trained both juvenile and adult snails with a single 0.5 h training session in CE and show that LTM was present 24 h later. Snails trained in a similar manner in just pond water show no LTM. We then asked if such training in CE conferred enhanced memory forming capabilities on these snails four weeks later. That is, would LTM be formed in these snails four weeks later following a single 0.5 h training session in pond water? We found that both adult and juvenile snails previously trained in CE one month previously had enhanced LTM formation abilities. The injection of a DNA methylation blocker, 5-AZA, prior to training in adult snails blocked enhanced LTM formation four weeks later. Finally, this enhanced LTM forming ability was not passed on to the next generation of snails. PMID:27138222

  14. Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis

    PubMed Central

    Pérez-García, Georgina; Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Bolaños-Jiménez, Francisco

    2016-01-01

    Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition. PMID:26882991

  15. Long-lasting enhancement of the delayed-type hypersensitivity response to heterologous erythrocytes in mice after a single injection of cyclophosphamide.

    PubMed Central

    Bovbjerg, D H; Ader, R; Cohen, N

    1986-01-01

    Previous reports have indicated that cyclophosphamide (CY) treatment can enhance delayed-type hypersensitivity (DTH) reactions by abrogating suppressor T cell functions. Such findings have suggested that cells in the suppressor lineage may be particularly sensitive to this alkylating agent. The experiments reported here demonstrate that a single injection of CY before sensitization can induce a long-lasting state of enhanced DTH responsiveness to sheep red blood cells (SRBC) in mice. This enhancement required concurrent antigenic stimulation and appeared to be antigen-specific. Additionally, CY treatment of sensitized mice before the first antigenic challenge for DTH resulted in suppressed responses to that challenge, followed by enhanced DTH to subsequent challenge with the same antigen. The suppressed response was achieved with a lower dose of CY than the subsequent enhancement and also required concurrent antigenic stimulation. These results indicate that the effects of CY on both effector and suppressor mechanisms are critically dependent upon antigenic stimulation, and suggest that apparent suppressor sensitivity to CY may be a function of differential ability to recover from CY treatment in a context of antigenic stimulation. PMID:2436841

  16. Emergence and long-lasting persistence of linezolid-resistant Enterococcus faecium-ST117 in an oncohematologic patient after a nine-day course of linezolid.

    PubMed

    Sánchez-Díaz, Ana María; Cuartero, Claudio; Lozano, Sara; Rodríguez, Juan Diego; Alonso, Juan Manuel; Quiles-Melero, Inmaculada; López, Javier; Cantón, Rafael; Ruiz-Garbajosa, Patricia

    2014-02-01

    We report the emergence and long-lasting persistence of linezolid resistance in an ampicillin-resistant Enterococcus faecium strain in the intestine of a neutropenic oncohematologic patient receiving chemotherapy. The patient was first colonized by an epidemic ampicillin-resistant E. faecium (ARE)-ST117 clustering into lineage 78. This clone exhibited resistance to levofloxacin, erythromycin and high-level resistance to streptomycin and gentamicin. After receiving treatment with several broad spectrum antibiotics for febrile neutropenia, a 9-day course of oral linezolid was administered once the patient developed bacteraemia by the same ARE colonizing clone. Linezolid-resistant ARE was detected 17 days later in the follow-up fecal samples and persisted 41 days after suppression of linezolid therapy. Resistance to linezolid was associated with G2576T transversion in the 23S rRNA and the presence of cfr gene was not detected. The persistence of G2576T-ARE strains, especially in oncohematologic patients with injured intestinal membranes, could increase the risk of bacteraemia. PMID:23987992

  17. History of Illicit Stimulant Use Is Not Associated with Long-Lasting Changes in Learning of Fine Motor Skills in Humans.

    PubMed

    Todd, Gabrielle; Pearson-Dennett, Verity; Flavel, Stanley C; Haberfield, Miranda; Edwards, Hannah; White, Jason M

    2016-01-01

    Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent individuals with a history of primarily methamphetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users (n = 21; 27 ± 6 yrs) and two gender-matched control groups comprising nondrug users (n = 16; 22 ± 4 yrs) and cannabis users (n = 16; 23 ± 5 yrs). Motor learning was assessed with a three-minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in individuals with a history of illicit stimulant use. PMID:26819778

  18. Luminescent properties of long lasting phosphor Ca{sub 2}MgSi{sub 2}O{sub 7}:Eu{sup 2+}

    SciTech Connect

    Gong Yu; Wang Yuhua; Jiang Ziqiang; Xu Xuhui; Li Yanqin

    2009-09-15

    Long afterglow phosphors (Ca{sub 1-x}Eu{sub x}){sub 2}MgSi{sub 2}O{sub 7} (0.002 {<=} x {<=} 0.02) were prepared by solid-state reactions under a weak reductive atmosphere. X-ray diffraction pattern, photoluminescence spectra, decay curve, afterglow spectra and thermoluminescence curves were investigated. The phosphors showed two emission peaks when they were excited by 343 nm, due to two types of Eu{sup 2+} centers existing in the Ca{sub 2}MgSi{sub 2}O{sub 7} lattice. However, only one emission peak can be found in their afterglow spectra. Energy transfer between Eu{sup 2+} ions in inequivalent sites was found. A possible mechanism was presented and discussed. The afterglow decay time of Ca{sub 1.998}MgSi{sub 2}O{sub 7}:Eu{sub 0.002} was nearly 12.5 h which means it was a good long lasting phosphor.

  19. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors.

    PubMed

    Mecha, M; Feliú, A; Iñigo, P M; Mestre, L; Carrillo-Salinas, F J; Guaza, C

    2013-11-01

    Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component. PMID:23851307

  20. History of Illicit Stimulant Use Is Not Associated with Long-Lasting Changes in Learning of Fine Motor Skills in Humans

    PubMed Central

    Todd, Gabrielle; Pearson-Dennett, Verity; Flavel, Stanley C.; Haberfield, Miranda; Edwards, Hannah; White, Jason M.

    2016-01-01

    Little is known about the long-lasting effect of use of illicit stimulant drugs on learning of new motor skills. We hypothesised that abstinent individuals with a history of primarily methamphetamine and ecstasy use would exhibit normal learning of a visuomotor tracking task compared to controls. The study involved three groups: abstinent stimulant users (n = 21; 27 ± 6 yrs) and two gender-matched control groups comprising nondrug users (n = 16; 22 ± 4 yrs) and cannabis users (n = 16; 23 ± 5 yrs). Motor learning was assessed with a three-minute visuomotor tracking task. Subjects were instructed to follow a moving target on a computer screen with movement of the index finger. Metacarpophalangeal joint angle and first dorsal interosseous electromyographic activity were recorded. Pattern matching was assessed by cross-correlation of the joint angle and target traces. Distance from the target (tracking error) was also calculated. Motor learning was evident in the visuomotor task. Pattern matching improved over time (cross-correlation coefficient) and tracking error decreased. However, task performance did not differ between the groups. The results suggest that learning of a new fine visuomotor skill is unchanged in individuals with a history of illicit stimulant use. PMID:26819778

  1. Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats.

    PubMed

    Pang, Yi; Tien, Lu-Tai; Zhu, Hobart; Shen, Juying; Wright, Camilla F; Jones, Tembra K; Mamoon, Samir A; Bhatt, Abhay J; Cai, Zhengwei; Fan, Lir-Wan

    2015-01-01

    Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure. PMID:25898410

  2. AMA1-Deficient Toxoplasma gondii Parasites Transiently Colonize Mice and Trigger an Innate Immune Response That Leads to Long-Lasting Protective Immunity

    PubMed Central

    Lagal, Vanessa; Dinis, Márcia; Cannella, Dominique; Bargieri, Daniel; Gonzalez, Virginie; Andenmatten, Nicole; Meissner, Markus

    2015-01-01

    The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until we genetically engineered viable parasites lacking AMA1. The reduction in invasiveness of the Toxoplasma gondii RH-AMA1 knockout (RH-AMA1KO) tachyzoite population, in vitro, raised key questions about the outcome associated with these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1KO tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leukocytes. While the RH-AMA1KO population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts, where immune cells in combination sense parasites and secrete proinflammatory cytokines. This innate response further leads to a long-lasting status immunoprotective against a secondary challenge by high inocula of the homologous type I or a distinct type II T. gondii genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population in vivo. PMID:25847964

  3. Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice.

    PubMed

    Wack, Andreas; Baudner, Barbara C; Hilbert, Anne K; Manini, Ilaria; Nuti, Sandra; Tavarini, Simona; Scheffczik, Hanno; Ugozzoli, Mildred; Singh, Manmohan; Kazzaz, Jina; Montomoli, Emanuele; Del Giudice, Giuseppe; Rappuoli, Rino; O'Hagan, Derek T

    2008-01-24

    Influenza is controlled by protective titres of neutralizing antibodies, induced with the help of CD4 T-cells, and by antiviral T-cell effector function. Adjuvants are essential for the efficient vaccination of a naïve population against avian influenza. We evaluated a range of adjuvants for their ability to enhance, in naïve mice, protective hemagglutination inhibition (HI) titres, which represent the generally accepted correlate of protection, virus-neutralizing titres and T-cell responses to a new generation influenza vaccine produced in cell culture. The selected adjuvants include alum, calcium phosphate (CAP), MF59, the delivery system poly-(lactide co-glycolide) (PLG) and the immune potentiator CpG. MF59 was clearly the most potent single adjuvant and induced significantly enhanced, long-lasting HI and neutralizing titres and T-cell responses in comparison to all alternatives. The combination of alum, MF59, CAP or PLG with CpG generally induced slightly more potent titres. The addition of CpG to MF59 also induced a more potent Th1 cellular immune response, represented by higher IgG2a titres and the induction of a strongly enhanced IFN-gamma response in splenocytes from immunized mice. These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains. PMID:18162266

  4. Microneedle Delivery of H5N1 Influenza Virus-Like Particles to the Skin Induces Long-Lasting B- and T-Cell Responses in Mice ▿

    PubMed Central

    Song, Jae-Min; Kim, Yeu-Chun; Lipatov, Aleksandr S.; Pearton, Marc; Davis, C. Todd; Yoo, Dae-Goon; Park, Kyoung-Mi; Chen, Li-Mei; Quan, Fu-Shi; Birchall, James C.; Donis, Ruben O.; Prausnitz, Mark R.; Compans, Richard W.; Kang, Sang-Moo

    2010-01-01

    A simple method suitable for self-administration of vaccine would improve mass immunization, particularly during a pandemic outbreak. Influenza virus-like particles (VLPs) have been suggested as promising vaccine candidates against potentially pandemic influenza viruses, as they confer long-lasting immunity but are not infectious. We investigated the immunogenicity and protective efficacy of influenza H5 VLPs containing the hemagglutinin (HA) of A/Vietnam/1203/04 (H5N1) virus delivered into the skin of mice using metal microneedle patches and also studied the response of Langerhans cells in a human skin model. Prime-boost microneedle vaccinations with H5 VLPs elicited higher levels of virus-specific IgG1 and IgG2a antibodies, virus-specific antibody-secreting cells, and cytokine-producing cells up to 8 months after vaccination compared to the same antigen delivered intramuscularly. Both prime-boost microneedle and intramuscular vaccinations with H5 VLPs induced similar hemagglutination inhibition titers and conferred 100% protection against lethal challenge with the wild-type A/Vietnam/1203/04 virus 16 weeks after vaccination. Microneedle delivery of influenza VLPs to viable human skin using microneedles induced the movement of CD207+ Langerhans cells toward the basement membrane. Microneedle vaccination in the skin with H5 VLPs represents a promising approach for a self-administered vaccine against viruses with pandemic potential. PMID:20631330

  5. Glucocorticoids alter neuronal differentiation of human neuroepithelial-like cells by inducing long-lasting changes in the reactive oxygen species balance.

    PubMed

    Raciti, Marilena; Ong, Jennie; Weis, Laura; Edoff, Karin; Battagli, Cristina; Falk, Anna; Ceccatelli, Sandra

    2016-08-01

    Prenatal exposure to excess glucocorticoid has been shown to have adverse effects on the developing nervous system that may lead to alterations of fetal and adult neurogenesis, resulting in behavioral changes. In addition, an imbalance of the redox state, with an increased susceptibility to oxidative stress, has been observed in rodent neural stem cells exposed to the synthetic glucocorticoid analog dexamethasone (Dex). In the present study, we used the induced pluripotent stem cells (IPSC)-derived lt-NES AF22 cell line, representative of the neuroepithelial stage in central nervous system development, to investigate the heritable effects of Dex on reactive oxygen species (ROS) balance and its impact on neuronal differentiation. By analysing gene expression in daughter cells that were never directly exposed to Dex, we could observe a downregulation of four key antioxidant enzymes, namely Catalase, superoxide dismutase 1, superoxide dismutase 2 and glutathione peroxidase7, along with an increased intracellular ROS concentration. The imbalance in the intracellular REDOX state was associated to a significant downregulation of major neuronal markers and a concomitant increase of glial cells. Interestingly, upon treatment with the antioxidant N-acetyl-cysteine (NAC), the misexpression of both neuronal and glial markers analyzed was recovered. These novel findings point to the increased ROS concentration playing a direct role in the heritable alterations of the differentiation potential induced by Dex exposure. Moreover, the data support the hypothesis that early insults may have detrimental long-lasting consequences on neurogenesis. Based on the positive effects exerted by NAC, it is conceivable that therapeutic strategies including antioxidants may be effective in the treatment of neuropsychiatric disorders that have been associated to increased ROS and impaired neurogenesis. PMID:26992751

  6. TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus.

    PubMed

    Yu, Shaoyong; Gao, Guofeng; Peterson, Blaise Z; Ouyang, Ann

    2009-07-01

    Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. Mast cell tryptase via protease-activated receptor 2 (PAR2)-mediated pathways sensitizes sensory nerves and induces hyperalgesia. Transient receptor potential A1 (TRPA1) plays an important role in mechanosensory transduction and nociception. Here we tested the hypothesis that mast cell activation via a PAR2-dependent mechanism sensitizes TRPA1 to induce mechanical hypersensitivity in esophageal vagal C-fibers. The expression profiles of PAR2 and TRPA1 in vagal nodose ganglia were determined by immunostaining, Western blot, and RT-PCR. Extracellular recordings from esophageal nodose neurons were performed in ex vivo guinea pig esophageal-vagal preparations. Action potentials evoked by esophageal distention and chemical perfusion were compared. Both PAR2 and TRPA1 expressions were identified in vagal nodose neurons by immunostaining, Western blot, and RT-PCR. Ninety-one percent of TRPA1-positive neurons were of small and medium diameters, and 80% coexpressed PAR2. Esophageal mast cell activation significantly enhanced the response of nodose C-fibers to esophageal distension (mechanical hypersensitivity). This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activation-induced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus. PMID:19423751

  7. Reconstruction of total grain size distribution of the climactic phase of a long-lasting eruption: the example of the 2008-2013 Chaitén eruption

    NASA Astrophysics Data System (ADS)

    Alfano, Fabrizio; Bonadonna, Costanza; Watt, Sebastian; Connor, Chuck; Volentik, Alain; Pyle, David M.

    2016-07-01

    The 2008-2013 eruption of Chaitén Volcano (Chile) was a long-lasting eruption whose climactic phase (May 6, 2008) produced a sub-Plinian plume, with height ranging between 14 and 20 km that dispersed to the NE, reaching the Atlantic coast of Argentina. The erupted material was mainly of lithic origin (˜77 wt%), resulting in a unimodal total grain size distribution (TGSD) dominated by coarse ash (77 wt%), with Mdϕ of 2.7 and σϕ of 2.4. Lapilli clasts (>2 mm) dominate the proximal deposit within ~20 km of the vent, while coarse (63 μm-2 mm) and fine ash (<63 μm) sedimented as far as 800 km from vent, generating mostly poly-modal grain size distributions across the entire deposit. Given that most of the mass is sedimented in proximal areas, results show that possible contributions of later explosive events to the thickness of the distal deposit where layers are less distinguishable (>400 km) do not significantly affect the determination of the TGSD. In contrast, gaps in data sampling in the medial deposit (in particular the gap between 50 and 350 km from vent that coincides with shifts in sedimentation regimes) have large impacts on estimates of TGSD. Particle number distribution for this deposit is characterized by a high power-law exponent (3.0) following a trend very similar to the vesicle size distribution in the juvenile pyroclasts. Although this could be taken to indicate a bubble-driven fragmentation process, we suggest that fragmentation was more likely the result of a shear-driven process because of the predominance of non-vesicular products (lithics and obsidians) and the large fraction of coarse ash in the TGSD.

  8. Genetically modified rabies virus ERA strain is safe and induces long-lasting protective immune response in dogs after oral vaccination.

    PubMed

    Shuai, Lei; Feng, Na; Wang, Xijun; Ge, Jinying; Wen, Zhiyuan; Chen, Weiye; Qin, Lide; Xia, Xianzhu; Bu, Zhigao

    2015-09-01

    Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG333E) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) were generated by reverse genetic. The recombinant virus rERAG333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12months after immunization. Dogs received oral vaccination with rERAG333E induced strong protective RABV VNA response, which lasted for over 3years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs. PMID:26093157

  9. Enhancement of long-lasting immunoprotective effect against Androctonus australis hector envenomation using safe antigens: Comparative role of MF59 and Alum adjuvants.

    PubMed

    Nouri, Abdelmounaim; Laraba-Djebari, Fatima

    2015-10-26

    Envenomation is a public health problem in many regions of the world. The only available treatment is the serotherapy that has limited efficiency due to the delay of its administration. The goal of this study is to provide a new and more efficient alternative to this treatment. A comparative study of the effects of two adjuvants in their ability to enhance the efficiency of the detoxified and safe antigens to produce a long lasting immunoprotection is undertaken using Aluminum Hydroxide adjuvant (Alum) or the water-in-oil MF59 adjuvant mixed with Androctonus australis hector (Aah) detoxified venom, and compare their effects on the immune system. Immunization schedule was performed with two groups of rabbits, which were injected with attenuated venom and Alum or MF59 adjuvant preparations, once a month during three months. Blood samples were collected each week for cell count, evaluation of myeloperoxidase (MPO) and eosinoperoxydase (EPO) activities and antibody titer. After four months from the last immunization, rabbits were challenged with increased doses of native Aah venom. Results showed that MF59 effect was immediate in the first 24h post-immunization by activating the recruitment of lymphocytes, monocytes and neutrophils, while Alum adjuvant effect seems to be delayed, and appeared in the second week after immunization. An important cell infiltration was observed with Alum preparation, due to its specific local depot effect. However, immunized animals with MF59 preparation challenged with the native venom showed a protective effect against its toxicity until 6 LD50 compared to those immunized with Alum preparation which are only protected at 4 LD50. One week after challenge, only immunized animals with Alum preparation present an increase in cell infiltration, MPO and EPO activities. These results are correlated with the ability of MF59 adjuvant to induce a potent immunoprotective effect against Aah venom compared to Alum adjuvant. PMID:26419199

  10. Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies.

    PubMed

    Hu, R L; Liu, Y; Zhang, S F; Zhang, F; Fooks, A R

    2007-07-20

    During the past decade, human rabies caused by cats has ranked the second highest in China. Several recombinant rabies vaccines have been developed for dogs. However, seldom have these vaccines been assessed or used in cats. In this trial, we report the experimental immunization of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Delta-RGP, in cats. Thirty cats were inoculated with the recombinant vaccine intramuscularly, orally and intranasally, respectively. Safety and efficacy studies were undertaken using the fluorescent antibody virus neutralization (FAVN) test and evaluated. Results showed that this recombinant vaccine is safe for cats as demonstrated by the three different routes of administration. The vaccine stimulated an efficient humoral response in the vaccinated cats when 10(8.5)PFU/ml of the recombinant vaccine was injected intramuscularly in a single dose. The neutralizing antibody level increased above 0.5IU/ml at 4 weeks after the vaccination. The mean antibody level ranged from 0.96+/-0.26 to 4.47+/-1.57IU/ml among individuals, and the antibody levels were elicited for at least 12 months. After this period, the immunized cats survived the challenge of CVS-24 and an obvious anemnestic and protective immune response was stimulated after the challenge. The immune response occurred later than the inactivated vaccine and the overall antibody level in the vaccinated cats was lower, but it was sufficient to confer protection of cats against infection. This demonstrated that a single, intramuscular dose of CAV-2-E3Delta-RGP stimulated a long-lasting protective immune response in cats and suggested that CAV-2-E3Delta-RGP could be considered as a potential rabies vaccine candidate for cats. PMID:17576027

  11. In utero exposure to di-(2-ethylhexyl) phthalate exerts both short-term and long-lasting suppressive effects on testosterone production in the rat.

    PubMed

    Culty, Martine; Thuillier, Raphael; Li, Wenping; Wang, Yan; Martinez-Arguelles, Daniel B; Benjamin, Carolina Gesteira; Triantafilou, Kostantinos M; Zirkin, Barry R; Papadopoulos, Vassilios

    2008-06-01

    We examined the effects of fetal exposure to a wide range of di-(2-ethylhexyl) phthalate (DEHP) doses on fetal, neonatal, and adult testosterone production. Pregnant rats were administered DEHP from Gestational Day (GD) 14 to the day of parturition (Postnatal Day 0). Exposure to between 234 and 1250 mg/kg/day of DEHP resulted in increases in the absolute volumes of Leydig cells per adult testis. Despite this, adult serum testosterone levels were reduced significantly compared to those of controls at all DEHP doses. Organ cultures of testes from GD20 rats exposed in utero to DEHP showed dose-dependent reductions in basal testosterone production. Surprisingly, however, no significant effect of DEHP was found on hCG-induced testosterone production by GD20 testes, suggesting that the inhibition of basal steroidogenesis resulted from the alteration of molecular events upstream of the steroidogenic enzymes. Reduced fetal and adult testosterone production in response to in utero DEHP exposure appeared to be unrelated to changes in testosterone metabolism. In view of the DEHP-induced reductions in adult testosterone levels, a decrease in the expression of steroidogenesis-related genes was anticipated. Surprisingly, however, significant increases were seen in the expression of Cyp11a1, Cy17a1, Star, and Tspo transcripts, suggesting that decreased testosterone production after birth could not be explained by decreases in steroidogenic enzymes as seen at GD20. These changes may reflect an increased number of Leydig cells in adult testes exposed in utero to DEHP rather than increased gene expression in individual Leydig cells, but this remains uncertain. Taken together, these results demonstrate that in utero DEHP exposure exerts both short-term and long-lasting effects on testicular steroidogenesis that might involve distinct molecular targets in fetal and adult Leydig cells. PMID:18322279

  12. Long-lasting effects of a PEGylated mutant cocaine esterase (CocE) on the reinforcing and discriminative stimulus effects of cocaine in rats.

    PubMed

    Collins, Gregory T; Narasimhan, Diwahar; Cunningham, Alyssa R; Zaks, Matthew E; Nichols, Joseph; Ko, Mei-Chuan; Sunahara, Roger K; Woods, James H

    2012-04-01

    Recent mutagenesis studies have identified a mutant G4C/S10C/T172R/G173Q cocaine esterase (CCRQ CocE) with an in vitro duration of action of >40 days. Although the in vivo duration of CCRQ CocE's action was <24 h, modification of this enzyme with polyethylene glycol (PEG) polymers resulted in a CocE (PEG-CCRQ CocE) capable of preventing cocaine-induced lethality for up to 72 h. The current studies were aimed at providing a detailed characterization of the effectiveness, selectivity, and duration of PEG-CCRQ CocE's actions in cocaine self-administration and discrimination assays in rats. Pretreatment with PEG-CCRQ CocE produced dose-dependent rightward shifts in the dose-response curves for cocaine self-administration and discrimination, with the highest dose of PEG-CCRQ CocE capable of producing an initial shift of cocaine's reinforcing and interoceptive effects of >30-fold to the right, with significant inhibition of these effects observed for up to 72 h. Although PEG-CCRQ CocE also produced slight reductions in the rates of methylphenidate- and food-reinforced responding, these effects were short-lived, lasting <24 h. Finally, when taken together with the finding that PEG-CCRQ CocE failed to alter the cocaine-like interoceptive effects of either methylphenidate or d-amphetamine, these results suggest that PEG-CCRQ CocE possesses a high degree of pharmacologic specificity for cocaine and a prolonged in vivo duration of action. In conclusion, these studies provide strong evidence to support the further development of long-lasting, highly efficient CocEs, such as PEG-CCRQ CocE, as a potential therapeutic option for the treatment of cocaine abuse in humans. PMID:21993206

  13. Syn-collisional granitoids in the Qilian Block on the Northern Tibetan Plateau: A long-lasting magmatism since continental collision through slab steepening

    NASA Astrophysics Data System (ADS)

    Huang, Hui; Niu, Yaoling; Mo, Xuanxue

    2016-03-01

    In this paper we present a new model that can explain the large zircon age spectrum of ~ 510 - 420 Ma within a single sample from the Gangcha (Gcha) biotite granodiorite and the Huangyuan (HY) two-mica monzogranite on the northern Tibetan Plateau. The large age spread recorded in zircons is characteristic of granitoid samples from the studied region, which is best explained by the long-lasting magmatism since the onset of continental collision at ~ 500 Ma, followed by slab steepening and the ultimate slab break-off at ~ 450 Ma. These granitoids have a large major and trace element compositional variation, but limited initial Sr (ISr[450] = 0.709 to 0.715), Nd (ԐNd[450] = - 6.5 to - 3.7), Hf (ԐHf[450] = - 4.3 to 1.5) and Pb (206Pb/204Pb[450] = 17.70 to 17.17; 207Pb/204Pb[450] = 15.60 to 15.69; 208Pb/204Pb[450] = 38.04 to 38.73) isotopic variation. The small negative whole rock ԐNd[450] and ԐHf[450] values are most consistent with the granitoid source being dominated by subducted seafloor materials. The inherited zircons with large negative ԐHf[450] values (e.g. - 50) are indicative of input from the lower continental crust and subducted sediments. The correlated variations among major elements, trace elements and radiogenic isotopes are best interpreted as reflecting melting-induced mixing of a compositionally heterogeneous source with superimposed effect of varying extent of fractional crystallization and crustal assimilation. The inherited zircons of Palaeo-Proterozoic age and the Archean crustal model ages signify the involvement of ancient basement rocks.

  14. Pre- and Postnatal Exposure to Moderate Levels of Ethanol Can Have Long-Lasting Effects on Hippocampal Glutamate Uptake in Adolescent Offspring

    PubMed Central

    de Souza, Daniela F.; Lopes, Fernanda M.; Leite, Marina C.; Gonçalves, Carlos-Alberto

    2015-01-01

    The developing brain is vulnerable to the effects of ethanol. Glutamate is the main mediator of excitatory signals in the brain and is probably involved in most aspects of normal brain function during development. The aim of this study was to investigate vulnerability to and the impact of ethanol toxicity on glutamate uptake signaling in adolescent rats after moderate pre and postnatal ethanol exposure. Pregnant female rats were divided into three groups and treated only with water (control), non-alcoholic beer (vehicle) or 10% (v/v) beer solution (moderate prenatal alcohol exposure—MPAE). Thirty days after birth, adolescent male offspring were submitted to hippocampal acute slice procedure. We assayed glutamate uptake and measured glutathione content and also quantified glial glutamate transporters (EAAT 1 and EAAT 2). The glutamate system vulnerability was tested with different acute ethanol doses in naïve rats and compared with the MPAE group. We also performed a (lipopolysaccharide-challenge (LPS-challenge) with all groups to test the glutamate uptake response after an insult. The MPAE group presented a decrease in glutamate uptake corroborating a decrease in glutathione (GSH) content. The reduction in GSH content suggests oxidative damage after acute ethanol exposure. The glial glutamate transporters were also altered after prenatal ethanol treatment, suggesting a disturbance in glutamate signaling. This study indicates that impairment of glutamate uptake can be dose-dependent and the glutamate system has a higher vulnerability to ethanol toxicity after moderate ethanol exposure In utero. The effects of pre- and postnatal ethanol exposure can have long-lasting impacts on the glutamate system in adolescence and potentially into adulthood. PMID:25978644

  15. Luminescence properties of tunable white-light long-lasting phosphor YPO4: Eu3+, Tb3+, Sr2+, Zr4+

    NASA Astrophysics Data System (ADS)

    Tang, Wei; Wang, Mingwen; Meng, Xiangxue; Lin, Wei

    2016-04-01

    A series of novel YPO4: Eu3+, Tb3+, Sr2+, Zr4+ tunable white-light long lasting phosphors were synthesized by conventional solid-state reaction method. The luminescent properties were systematically characterized by X-ray diffraction, photoluminescent excitation and emission spectra, thermoluminescence spectrum and decay curves. The XRD patterns indicated that the samples belonged to tetragonal phase and co-doping Eu3+, Tb3+, Sr2+ and Zr4+ ions have no effect on the basic crystal structure. Under the excitation of 372 nm wavelength, it was first discovered that the specific concentration of Sr2+ can improve the emission intensity of Eu2+. The blue (Eu2+), green (Tb3+) and red (Eu3+) lights were emitted simultaneously and therefore produced white light in the same YPO4 matrix. Tunable color from the white to purple region was achieved not only by increasing the concentration of Zr4+ and Sr2+, but also by increasing the concentration of Eu3+. The CIE chromaticity coordinates of Y0.89PO4: Eu3+0.06, Tb3+0.05, Sr2+0.06, Zr4+0.06 (0.33, 0.31) were the closest to point (0.33, 0.33) which delegates the ideal white and trap depths for the two glow peaks are 0.88 eV and 0.85 eV. The fitting decay constant of τ2 corresponding to the slow exponentially decay components was 101.30 s.

  16. BU08073 a buprenorphine analogue with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice

    PubMed Central

    Khroyan, T V; Wu, J; Polgar, W E; Cami-Kobeci, G; Fotaki, N; Husbands, S M; Toll, L

    2015-01-01

    BACKGROUND AND PURPOSE Buprenorphine is a potent analgesic with high affinity at μ, δ and κ and moderate affinity at nociceptin opioid (NOP) receptors. Nevertheless, NOP receptor activation modulates the in vivo activity of buprenorphine. Structure activity studies were conducted to design buprenorphine analogues with high affinity at each of these receptors and to characterize them in in vitro and in vivo assays. EXPERIMENTAL APPROACH Compounds were tested for binding affinity and functional activity using [35S]GTPγS binding at each receptor and a whole-cell fluorescent assay at μ receptors. BU08073 was evaluated for antinociceptive agonist and antagonist activity and for its effects on anxiety in mice. KEY RESULTS BU08073 bound with high affinity to all opioid receptors. It had virtually no efficacy at δ, κ and NOP receptors, whereas at μ receptors, BU08073 has similar efficacy as buprenorphine in both functional assays. Alone, BU08073 has anxiogenic activity and produces very little antinociception. However, BU08073 blocks morphine and U50,488-mediated antinociception. This blockade was not evident at 1 h post-treatment, but is present at 6 h and remains for up to 3–6 days. CONCLUSIONS AND IMPLICATIONS These studies provide structural requirements for synthesis of ‘universal’ opioid ligands. BU08073 had high affinity for all the opioid receptors, with moderate efficacy at μ receptors and reduced efficacy at NOP receptors, a profile suggesting potential analgesic activity. However, in vivo, BU08073 had long-lasting antagonist activity, indicating that its pharmacokinetics determined both the time course of its effects and what receptor-mediated effects were observed. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24903063

  17. The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy')-induced degeneration of 5-HT nerve endings in rat brain

    PubMed Central

    Sanchez, V; Camarero, J; Esteban, B; Peter, M J; Green, A R; Colado, M I

    2001-01-01

    It has been reported that co-administration of fluoxetine with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') prevents MDMA-induced degeneration of 5-HT nerve endings in rat brain. The mechanisms involved have now been investigated. MDMA (15 mg kg−1, i.p.) administration produced a neurotoxic loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, hippocampus and striatum and a reduction in cortical [3H]-paroxetine binding 7 days later. Fluoxetine (10 mg kg−1, i.p., ×2, 60 min apart) administered concurrently with MDMA or given 2 and 4 days earlier provided complete protection, and significant protection when given 7 days earlier. Fluvoxamine (15 mg kg−1, i.p., ×2, 60 min apart) only produced neuroprotection when administered concurrently. Fluoxetine (10 mg kg−1, ×2) markedly increased the KD and reduced the Bmax of cortical [3H]-paroxetine binding 2 and 4 days later. The Bmax was still decreased 7 days later, but the KD was unchanged. [3H]-Paroxetine binding characteristics were unchanged 24 h after fluvoxamine (15 mg kg−1, ×2). A significant cerebral concentration of fluoxetine plus norfluoxetine was detected over the 7 days following fluoxetine administration. The fluvoxamine concentration had decreased markedly by 24 h. Pretreatment with fluoxetine (10 mg kg−1, ×2) failed to alter cerebral MDMA accumulation compared to saline pretreated controls. Neither fluoxetine or fluvoxamine altered MDMA-induced acute hyperthermia. These data demonstrate that fluoxetine produces long-lasting protection against MDMA-induced neurodegeneration, an effect apparently related to the presence of the drug and its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter the metabolism of MDMA or its rate of cerebral accumulation. PMID:11522596

  18. A long-lasting protective immunity against chronic toxoplasmosis in mice induced by recombinant rhoptry proteins encapsulated in poly (lactide-co-glycolide) microparticles.

    PubMed

    Xu, Ying; Zhang, Nian-Zhang; Wang, Meng; Dong, Hu; Feng, Sheng-Yong; Guo, Hui-Chen; Zhu, Xing-Quan

    2015-11-01

    Toxoplasma gondii infection in humans and animals is a worldwide zoonosis. Prevention and control of toxoplasmosis based on vaccination is one of the promising strategies. In the present study, recombinant T. gondii rhoptry proteins 38 and 18 (TgROP38 and TgROP18) were encapsulated into poly (lactide-co-glycolide) (PLG) (1:1), respectively, to obtain the stable water-in-oil-in-water double emulsion. Female Kunming mice were then immunized with the protein vaccines twice at a 2-week interval. Eight weeks after the second immunization, 10 mice from each group were challenged with T. gondii PRU strain (genotype II). The entrapment rates of PLG-rROP38 and PLG-rROP18 ranged from 65.5 to 77.7% and 58.1 to 72.3%, respectively. Immunization of mice with rROP38 and rROP18 proteins encapsulated into PLG microparticles elicited strongly humoral and cell-mediated responses against T. gondii, associated with relatively high levels of total IgG, IgG2a isotype, and IFN-γ, as well as the mixed Th1/Th2 immunity responses. Immunization with various protein vaccines induced significant reduction of the brain cysts after chronic infection with the T. gondii PRU strain, and the most effective protection was achieved in the PLG-rROP38-rROP18-immunized mice, with a cyst reduction of 81.3%. The findings of the present study indicated that recombinant rhoptry antigens encapsulated in PLG could maintain the protein immunogenicity in an extended period and elicit effective protection against chronic T. gondii infection, which has implications for the development of long-lasting vaccines against chronic toxoplasmosis in animals. PMID:26243574

  19. Long-lasting hypoglycemic effect of modified FGF-21 analog with polyethylene glycol in type 1 diabetic mice and its systematic toxicity.

    PubMed

    Ye, Xianlong; Qi, Jianying; Wu, Qiang; Yu, Dan; Li, Shujie; Wu, Yunzhou; Li, Deshan

    2016-06-15

    Fibroblast growth factor-21 (FGF-21) is a novel metabolic regulator and has the potential to become a powerful therapy to treat diabetes mellitus. However, we found that the clinical application of wild type FGF-21 was influenced by its low intrinsic bio-stability and poor hypoglycemic potency. In this study, The N-terminus of FGF-21 analog (mFGF-21) was PEGylated in a site-specific manner by 20kD methoxy poly-ethylene glycol-propionaldehyde (mPEG-ALD). PEGylated mFGF-21 was isolated by Capto Q anion exchange chromatography. The properties of PEGylated mFGF-21 including the in vitro bio-stability and biological activity were evaluated. As well as the anti-diabetic effect of PEGylated mFGF-21 were studied in streptozotocin (STZ)-induced type 1 diabetic mice. Results demonstrated that PEGylated mFGF-21 had a similar capacity of stimulating glucose uptake in HepG2 cells with mFGF-21 and PEGylation of mFGF-21 significantly enhanced the anti-protease ability and the long acting anti-diabetic effect in type 1 diabetic mice. Furthermore, the preliminary safety of PEGylated mFGF-21 following subcutaneously injection was assessed using healthy mice by measuring the body weight, histopathology and clinical biochemical parameters, and the results showed no subacute toxicity to major organs or tissues and no significant changes in physiological and biochemical parameters in healthy mice. Taken together, under the premise of remaining the in vitro biological activity of mFGF-21, PEGylation significantly improves the long lasting hypoglycemic effect of mFGF-21 in type 1 diabetic mice. Our valuation shows that PEGylated mFGF-21 is a potential drug for the effective treatment of type 1 diabetes. PMID:27089817

  20. Calcium permeable AMPA receptor-dependent long lasting plasticity of intrinsic excitability in fast spiking interneurons of the dentate gyrus decreases inhibition in the granule cell layer.

    PubMed

    Dasgupta, Debanjan; Sikdar, Sujit Kumar

    2015-03-01

    The local fast-spiking interneurons (FSINs) are considered to be crucial for the generation, maintenance, and modulation of neuronal network oscillations especially in the gamma frequency band. Gamma frequency oscillations have been associated with different aspects of behavior. But the prolonged effects of gamma frequency synaptic activity on the FSINs remain elusive. Using whole cell current clamp patch recordings, we observed a sustained decrease of intrinsic excitability in the FSINs of the dentate gyrus (DG) following repetitive stimulations of the mossy fibers at 30 Hz (gamma bursts). Surprisingly, the granule cells (GCs) did not express intrinsic plastic changes upon similar synaptic excitation of their apical dendritic inputs. Interestingly, pairing the gamma bursts with membrane hyperpolarization accentuated the plasticity in FSINs following the induction protocol, while the plasticity attenuated following gamma bursts paired with membrane depolarization. Paired pulse ratio measurement of the synaptic responses did not show significant changes during the experiments. However, the induction protocols were accompanied with postsynaptic calcium rise in FSINs. Interestingly, the maximum and the minimum increase occurred during gamma bursts with membrane hyperpolarization and depolarization respectively. Including a selective blocker of calcium-permeable AMPA receptors (CP-AMPARs) in the bath; significantly attenuated the calcium rise and blocked the membrane potential dependence of the calcium rise in the FSINs, suggesting their involvement in the observed phenomenon. Chelation of intracellular calcium, blocking HCN channel conductance or blocking CP-AMPARs during the experiment forbade the long lasting expression of the plasticity. Simultaneous dual patch recordings from FSINs and synaptically connected putative GCs confirmed the decreased inhibition in the GCs accompanying the decreased intrinsic excitability in the FSINs. Experimentally constrained network

  1. Photostimulation of retrotrapezoid nucleus Phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats

    PubMed Central

    Abbott, Stephen B.G.; Stornetta, Ruth L.; Fortuna, Michal G.; Depuy, Seth D.; West, Gavin H.; Harris, Thurl E.; Guyenet, Patrice G.

    2009-01-01

    SUMMARY The retrotrapezoid “nucleus” (RTN), located in the rostral ventrolateral medullary reticular formation, contains a bilateral cluster of about 1000 glutamatergic non catecholaminergic Phox2b-expressing propriobulbar neurons that are activated by CO2 in vivo and by acidification in vitro. These cells are thought to function as central respiratory chemoreceptors but this theory still lacks a crucial piece of evidence, namely that stimulating these particular neurons selectively in vivo increases breathing. The present study carried out in anesthetized rats seeks to test whether this expectation is correct. We injected into the left RTN a lentivirus that expresses the light-activated cationic channel channelrhodopsin-2 (ChR2, H134R mutation, fused to the fluorescent protein mCherry) under the control of the Phox2-responsive promoter PRSx8. Transgene expression was restricted to 423 ± 38 Phox2b-expressing neurons per rat consisting of non-catecholaminergic and C1 adrenergic neurons (3/2 ratio). Photostimulation delivered to the RTN region in vivo via a fiberoptic activated the CO2-sensitive neurons vigorously, produced a long-lasting (t1/2 = 11 s) increase in phrenic nerve activity and caused a small and short-lasting cardiovascular stimulation. Selective lesions of the C1 cells eliminated the cardiovascular response but left the respiratory stimulation intact. In rats with C1 cell lesions, the mCherry-labeled axon terminals originating from the transfected non-catecholaminergic neurons were present exclusively in the lower brainstem regions that contain the respiratory pattern generator. These results provide strong evidence that the Phox2b-expressing non-catecholaminergic neurons of the RTN region function as central respiratory chemoreceptors. PMID:19420248

  2. Long-lasting distortion of GABA signaling in MS/DB neurons after binge-like ethanol exposure during initial synaptogenesis.

    PubMed

    Wang, Haiying; DuBois, Dustin W; Tobery, Angelika N; Griffith, William H; Brandt, Paul; Frye, Gerald D

    2013-07-01

    Using a well-established model of binge-like ethanol treatment of rat pups on postnatal days (PD) 4-9, we found that maturation of GABAA receptor (GABAAR) miniature postsynaptic currents (mPSCs) was substantially blunted for medial septum/diagonal band (MS/DB) neurons in brain slices on PD 11-16. Ethanol reduced mPSC amplitude, frequency, and decay kinetics, while attenuating or exaggerating allosteric actions of zolpidem and allopregnanolone, respectively. The impact of ethanol in vivo was long lasting as most changes in MS/DB GABAAR mPSCs were still observed as late as PD 60-85. Maturing MS/DB neurons in naïve brain slices PD 4-16 showed increasing mPSC frequency, decay kinetics, and zolpidem sensitivity that were nearly identical to our earlier findings in cultured septal neurons (DuBois et al., 2004, 2006). These rapidly developing mPSC parameters continued to mature through the first month of life then stabilized throughout the remainder of the lifespan. Finally, equivalent ethanol-induced alterations in GABAAR mPSC signaling were present in MS/DB neurons from both male and female animals. Previously, we showed ethanol treatment of cultured embryonic day 20 septal neurons distorts the maturation of GABAAR mPSCs predicting that early stages of GABAergic transmission in MS/DB neurons are vulnerable to intoxication injury (DuBois et al., 2004, 2006). Since the overall character, timing, and magnitude of GABAergic mPSC developmental- and ethanol-induced changes in the in vivo model so closely mirror chronologically equivalent adaptations in cultured septal neurons, this suggests that such parallel models of ethanol impairment of GABAergic synaptic development in vivo and in vitro should be useful for translational studies exploring the efficacy and mechanism of action of potential therapeutic interventions from the cellular to whole animal level. PMID:23685190

  3. Spinal astrocytic activation contributes to both induction and maintenance of pituitary adenylate cyclase-activating polypeptide type 1 receptor-induced long-lasting mechanical allodynia in mice

    PubMed Central

    Yokai, Masafumi; Miyata, Atsuro

    2016-01-01

    Background Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are present in the spinal dorsal horn and dorsal root ganglia, suggesting an important role of PACAP–PACAP receptors signaling system in the modulation of spinal nociceptive transmission. We have previously reported that a single intrathecal injection of PACAP or a PACAP specific (PAC1) receptor selective agonist, maxadilan, in mice induced dose-dependent aversive behaviors, which lasted more than 30 min, and suggested that the maintenance of the nociceptive behaviors was associated with the spinal astrocytic activation. Results We found that a single intrathecal administration of PACAP or maxadilan also produced long-lasting hind paw mechanical allodynia, which persisted at least 84 days without affecting thermal nociceptive threshold. In contrast, intrathecal application of vasoactive intestinal polypeptide did not change mechanical threshold, and substance P, calcitonin gene-related peptide, or N-methyl-D-aspartate induced only transient mechanical allodynia, which disappeared within 21 days. Western blot and immunohistochemical analyses with an astrocytic marker, glial fibrillary acidic protein, revealed that the spinal PAC1 receptor stimulation caused sustained astrocytic activation, which also lasted more than 84 days. Intrathecal co-administration of L-α-aminoadipate, an astroglial toxin, with PACAP or maxadilan almost completely prevented the induction of the mechanical allodynia. Furthermore, intrathecal treatment of L-α-aminoadipate at 84 days after the PAC1 stimulation transiently reversed the mechanical allodynia accompanied by the reduction of glial fibrillary acidic protein expression level. Conclusion Our data suggest that spinal astrocytic activation triggered by the PAC1 receptor stimulation contributes to both induction and maintenance of the long-term mechanical allodynia. PMID:27175011

  4. Long-lasting neuroprotection and neurological improvement in stroke models with new, potent and brain permeable inhibitors of poly(ADP-ribose) polymerase

    PubMed Central

    Moroni, F; Cozzi, A; Chiarugi, A; Formentini, L; Camaioni, E; Pellegrini-Giampietro, DE; Chen, Y; Liang, S; Zaleska, MM; Gonzales, C; Wood, A; Pellicciari, R

    2012-01-01

    BACKGROUND AND PURPOSES Thienyl-isoquinolone (TIQ-A) is a relatively potent PARP inhibitor able to reduce post-ischaemic neuronal death in vitro. Here we have studied, in different stroke models in vivo, the neuroprotective properties of DAMTIQ and HYDAMTIQ, two TIQ-A derivatives able to reach the brain and to inhibit PARP-1 and PARP-2. EXPERIMENTAL APPROACH Studies were carried out in (i) transient (2 h) middle cerebral artery occlusion (tMCAO), (ii) permanent MCAO (pMCAO) and (iii) electrocoagulation of the distal portion of MCA in conjunction with transient (90 min) bilateral carotid occlusion (focal cortical ischaemia). KEY RESULTS In male rats with tMCAO, HYDAMTIQ (0.1–10 mg·kg−1) injected i.p. three times, starting 4 h after MCAO, reduced infarct volumes by up to 70%, reduced the loss of body weight by up to 60% and attenuated the neurological impairment by up to 40%. In age-matched female rats, HYDAMTIQ also reduced brain damage. Protection, however, was less pronounced than in the male rats. In animals with pMCAO, HYDAMTIQ administered 30 min after MCAO reduced infarct volumes by approximately 40%. In animals with focal cortical ischaemia, HYDAMTIQ treatment decreased post-ischaemic accumulation of PAR (the product of PARP activity) and the presence of OX42-positive inflammatory cells in the ischaemic cortex. It also reduced sensorimotor deficits for up to 90 days after MCAO. CONCLUSION AND IMPLICATIONS Our results show that HYDAMTIQ is a potent PARP inhibitor that conferred robust neuroprotection and long-lasting improvement of post-stroke neurological deficits. PMID:21913897

  5. Co-Transplantation of Endothelial Progenitor Cells and Pancreatic Islets to Induce Long-Lasting Normoglycemia in Streptozotocin-Treated Diabetic Rats

    PubMed Central

    Spiga, Saturnino; Mazzanti, Benedetta; Curcio, Michele; Mulas, Giovanna; Diana, Marco; Marzola, Pasquina; Mosca, Franco; Longoni, Biancamaria

    2014-01-01

    Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards. PMID:24733186

  6. Co-transplantation of endothelial progenitor cells and pancreatic islets to induce long-lasting normoglycemia in streptozotocin-treated diabetic rats.

    PubMed

    Quaranta, Paola; Antonini, Sara; Spiga, Saturnino; Mazzanti, Benedetta; Curcio, Michele; Mulas, Giovanna; Diana, Marco; Marzola, Pasquina; Mosca, Franco; Longoni, Biancamaria

    2014-01-01

    Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3-5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards. PMID:24733186

  7. Long-term insecticidal activity and physical integrity of Olyset nets in Tafea Province, Vanuatu.

    PubMed

    Dutta, Shurajit N; Amon, James; Iata, Harry; Cooper, Robert D; Russell, Tanya L

    2014-01-01

    The long-term efficacy of long-lasting insecticidal nets (LLINs) depends on both the physical condition of the net and the residual activity of the insecticide. This study focused on monitoring these parameters in Olyset nets (Sumitomo Chemical Co., Osaka, Japan) (n = 101) that had been used for 1-3 yr in Tafea Province, Vanuatu. Net usage and frequency of washing was ascertained by questionnaire; the nets were assessed with regards to cleanliness and damage owing to holes. Insecticide efficacy was determined with cone bioassays using Anophelesfarauti Laveran. Net usage was high and 86.1% (87 of 101) of villages stated that they used the net every night. Washing of nets was low (11.9%, 12 of 101), and most nets (79.2%, 80 of 101) were considered dirty. Most nets were damaged (73.4% had holes), and 22.8% (23 of 101) had large holes (>200 cm2). The 24-h mortality of An. farauti exposed to nets aged 1-2 yr was 79.4%, while the mortality for nets 3 yr of age was significantly lower at 73.7%. There was no difference in the insecticidal activity of clean compared with dirty nets (mean 24-h mortality: Clean = 76.7%, Dirty = 77.1%). Although the majority of nets had holes, the physical condition of 8.9-22.8% of nets was altered so severely to potentially affect efficacy. Although the 3-yr-old nets would still be providing significant levels of insecticidal and personal protection, consideration should be given to replacing nets >3 yr old. PMID:24605466

  8. Injection of household spray insecticide.

    PubMed

    Goldberg, L H; Shupp, D; Weitz, H H; Zeccardi, J A

    1982-11-01

    During a three-week period, two patients who had attempted suicide by injecting themselves with commercially available household spray insecticides were seen in our emergency department. Both presented with cellulitis at and adjacent to the injection sites, and both were admitted for intravenous antibiotics, warm soaks, and elevation. In both patients abscesses subsequently developed in the areas of cellulitis. It is not clear whether the pathologic processes in these two patients were primarily due to inoculation of microorganisms or to the effects of the insecticide per se. PMID:7137672

  9. Bradyzide, a potent non-peptide B2 bradykinin receptor antagonist with long-lasting oral activity in animal models of inflammatory hyperalgesia

    PubMed Central

    Burgess, Gillian M; Perkins, Martin N; Rang, Humphrey P; Campbell, Elizabeth A; Brown, Michael C; McIntyre, Peter; Urban, Laszlo; Dziadulewicz, Edward K; Ritchie, Timothy J; Hallett, Allan; Snell, Christopher R; Wrigglesworth, Roger; Lee, Wai; Davis, Clare; Phagoo, Steve B; Davis, Andrew J; Phillips, Elsa; Drake, Gillian S; Hughes, Glyn A; Dunstan, Andrew; Bloomfield, Graham C

    2000-01-01

    Bradyzide is from a novel class of rodent-selective non-peptide B2 bradykinin antagonists (1-(2-Nitrophenyl)thiosemicarbazides). Bradyzide has high affinity for the rodent B2 receptor, displacing [3H]-bradykinin binding in NG108-15 cells and in Cos-7 cells expressing the rat receptor with KI values of 0.51±0.18 nM (n=3) and 0.89±0.27 nM (n=3), respectively. Bradyzide is a competitive antagonist, inhibiting B2 receptor-induced 45Ca efflux from NG108-15 cells with a pKB of 8.0±0.16 (n=5) and a Schild slope of 1.05. In the rat spinal cord and tail preparation, bradyzide inhibits bradykinin-induced ventral root depolarizations (IC50 value; 1.6±0.05 nM (n=3)). Bradyzide is much less potent at the human than at the rodent B2 receptor, displacing [3H]-bradykinin binding in human fibroblasts and in Cos-7 cells expressing the human B2 receptor with KI values of 393±90 nM (n=3) and 772±144 nM (n=3), respectively. Bradyzide inhibits bradykinin-induced [3H]-inositol trisphosphate (IP3) formation with IC50 values of 11.6±1.4 nM (n=3) at the rat and 2.4±0.3 μM (n=3) at the human receptor. Bradyzide does not interact with a range of other receptors, including human and rat B1 bradykinin receptors. Bradyzide is orally available and blocks bradykinin-induced hypotension and plasma extravasation. Bradyzide shows long-lasting oral activity in rodent models of inflammatory hyperalgesia, reversing Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in the rat knee joint (ED50, 0.84 μmol kg−1; duration of action >4 h). It is equipotent with morphine and diclofenac, and 1000 times more potent than paracetamol, its maximal effect exceeding that of the non-steroidal anti-inflammatory drugs (NSAIDs). Bradyzide does not exhibit tolerance when administered over 6 days. In summary, bradyzide is a potent, orally active, antagonist of the B2 bradykinin receptor, with selectivity for the rodent over the human receptor. PMID:10694205

  10. Tumor Mouse Model Confirms MAGE-A3 Cancer Immunotherapeutic As an Efficient Inducer of Long-Lasting Anti-Tumoral Responses

    PubMed Central

    Gérard, Catherine; Baudson, Nathalie; Ory, Thierry; Louahed, Jamila

    2014-01-01

    Purpose MAGE-A3 is a potential target for immunotherapy due to its tumor-specific nature and expression in several tumor types. Clinical data on MAGE-A3 immunotherapy have raised many questions that can only be addressed by using animal models. In the present study, different aspects of the murine anti-tumor immune responses induced by a recombinant MAGE-A3 protein (recMAGE-A3) in combination with different immunostimulants (AS01, AS02, CpG7909 or AS15) were investigated. Experimental Design and Results Based on cytokine profile analyses and protection against challenge with MAGE-A3-expressing tumor, the combination recMAGE-A3+AS15 was selected for further experimental work, in particular to study the mechanisms of anti-tumor responses. By using MHC class I-, MHC class II-, perforin-, B-cell- and IFN-γ- knock-out mice and CD4+ T cell-, CD8+ T cell- and NK cell- depleted mice, we demonstrated that CD4+ T cells and NK cells are the main anti-tumor effectors, and that IFN-γ is a major effector molecule. This mouse tumor model also established the need to repeat recMAGE-A3+AS15 injections to sustain efficient anti-tumor responses. Furthermore, our results indicated that the efficacy of tumor rejection by the elicited anti-MAGE-A3 responses depends on the proportion of tumor cells expressing MAGE-A3. Conclusions The recMAGE-A3+AS15 cancer immunotherapy efficiently induced an antigen-specific, functional and long-lasting immune response able to recognize and eliminate MAGE-A3-expressing tumor cells up to several months after the last immunization in mice. The data highlighted the importance of the immunostimulant to induce a Th1-type immune response, as well as the key role played by IFN-γ, CD4+ T cells and NK cells in the anti-tumoral effect. PMID:24830315

  11. Insecticide resistance and dominance levels.

    PubMed

    Bourguet, D; Genissel, A; Raymond, M

    2000-12-01

    Dominance has been assessed in different ways in insecticide resistance studies, based on three phenotypic traits: the insecticide concentration required to give a particular mortality (DLC), mortality at a particular insecticide dose (DML), and fitness in treated areas (DWT). We propose a general formula for estimating dominance on a scale of 0 to 1 (0 = complete recessivity and 1 = complete dominance). DLC, DML, and DWT are not directly related and their values depend on genetic background and environmental conditions. We also show that pest management strategies can have the consequence to increase DWT via the selection of dominance modifiers. Studies on resistance to Bacillus thuringiensis toxins provide the ultimate example of the complexity of the definition of the concept of dominance. Almost all studies have focused on calculation of DLC, which provides little information about the efficiency of pest management programs. For instance, one assumption of the high dose/refuge strategy is that Bacillus thuringiensis resistance must be effectively recessive (i.e., DML must be close to zero). However, DWT, rather than DML, is relevant to the resistance management strategy. Therefore, we strongly suggest that the time has come to focus on fitness dominance levels in the presence and absence of insecticide. PMID:11142285

  12. Pyrethrum flowers and pyrethroid insecticides.

    PubMed Central

    Casida, J E

    1980-01-01

    The natural pyrethrins from the daisy-like flower, Tanacetum or Chrysanthemum cinerariifolium, are nonpersistent insecticides of low toxicity to mammals. Synthetic analogs or pyrethroids, evolved from the natural compounds by successive isosteric modifications, are more potent and stable and are the newest important class of crop protection chemicals. They retain many of the favorable properties of the pyrethrins. PMID:6993201

  13. Limonene--A Natural Insecticide.

    ERIC Educational Resources Information Center

    Beatty, Joseph H.

    1986-01-01

    Describes a high school chemistry student's research project in which limonene was isolated from the oil of lemons and oranges. Outlines the students' tests on the use of this chemical as an insecticide. Discusses possible extensions of the exercises based on questions generated by the students. (TW)

  14. Bioassays for Monitoring Insecticide Resistance

    PubMed Central

    Miller, Audra L.E.; Tindall, Kelly; Leonard, B. Rogers

    2010-01-01

    Pest resistance to pesticides is an increasing problem because pesticides are an integral part of high-yielding production agriculture. When few products are labeled for an individual pest within a particular crop system, chemical control options are limited. Therefore, the same product(s) are used repeatedly and continual selection pressure is placed on the target pest. There are both financial and environmental costs associated with the development of resistant populations. The cost of pesticide resistance has been estimated at approximately $ 1.5 billion annually in the United States. This paper will describe protocols, currently used to monitor arthropod (specifically insects) populations for the development of resistance. The adult vial test is used to measure the toxicity to contact insecticides and a modification of this test is used for plant-systemic insecticides. In these bioassays, insects are exposed to technical grade insecticide and responses (mortality) recorded at a specific post-exposure interval. The mortality data are subjected to Log Dose probit analysis to generate estimates of a lethal concentration that provides mortality to 50% (LC50) of the target populations and a series of confidence limits (CL's) as estimates of data variability. When these data are collected for a range of insecticide-susceptible populations, the LC50 can be used as baseline data for future monitoring purposes. After populations have been exposed to products, the results can be compared to a previously determined LC50 using the same methodology. PMID:21248689

  15. The biology of insecticidal activity and resistance.

    PubMed

    Perry, Trent; Batterham, Philip; Daborn, Phillip J

    2011-07-01

    Identifying insecticide resistance mechanisms is paramount for pest insect control, as the understandings that underpin insect control strategies must provide ways of detecting and managing resistance. Insecticide resistance studies rely heavily on detailed biochemical and genetic analyses. Although there have been many successes, there are also many examples of resistance that still challenge us. As a precursor to rational pest insect control, the biology of the insect, within the contexts of insecticide modes of action and insecticide metabolism, must be well understood. It makes sense to initiate this research in the best model insect system, Drosophila melanogaster, and translate these findings and methodologies to other insects. Here we explore the usefulness of the D. melanogaster model in studying metabolic-based insecticide resistances, target-site mediated resistances and identifying novel insecticide targets, whilst highlighting the importance of having a more complete understanding of insect biology for insecticide studies. PMID:21426939

  16. Combining Indoor Residual Spraying and Insecticide-Treated Net Interventions

    PubMed Central

    Kleinschmidt, Immo; Schwabe, Christopher; Shiva, Murugasampilay; Segura, Jose Luis; Sima, Victor; Mabunda, Samuel Jose Alves; Coleman, Michael

    2013-01-01

    Does scaling up of malaria control by combining indoor residual spraying (IRS) and long-lasting insecticidal nets (LLIN) enhance protection to populations? Results from a literature search and from recent household surveys in Bioko, Equatorial Guinea, and Zambezia, Mozambique are presented. Five out of eight previous studies reported a reduced risk of infection in those protected by both interventions compared with one intervention alone. Surveys in Bioko and Zambezia showed strong evidence of a protective effect of IRS combined with nets relative to IRS alone (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.59–0.86 for Bioko, and OR = 0.63, 95% CI = 0.50–0.79, for Zambezia). The effect of both interventions combined, compared with those who had neither, was OR = 0.46, (95% CI = 0.76–0.81) in Bioko and 0.34 (95% CI = 0.21–0.56) in Zambezia. Although the effects of confounding cannot be excluded, these results provide encouragement that the additional resources for combining IRS and LLIN are justified. PMID:19706925

  17. Toxicity of Insecticides on Various Life Stages of Two Tortricid Pests of Cranberries and on a Non-Target Predator

    PubMed Central

    Rodriguez-Saona, Cesar; Wanumen, Andrea Carolina; Salamanca, Jordano; Holdcraft, Robert; Kyryczenko-Roth, Vera

    2016-01-01

    Laboratory and extended laboratory bioassays were conducted to determine the residual toxicities of various insecticides against two key pests of cranberries, Sparganothis sulfureana and Choristoneura parallela (Lepidoptera: Tortricidae), and their non-target effects on the predatory Orius insidiosus (Hemiptera: Anthocoridae). The effects of nine insecticides with different modes of action on S. sulfureana and Ch. parallela eggs, larvae, and adults were tested in the laboratory, while the efficacy of a post-bloom application on larval mortality and mass of these pests and on adult O. insidiosus was evaluated in extended laboratory experiments. The organophosphate chlorpyrifos and the spinosyn spinetoram provided long-lasting (seven-day) control against all stages of both pests. The growth regulator methoxyfenozide and the diamides chlorantraniliprole and cyantraniliprole had strong (1–7 days) larvicidal, particularly on young larvae, and growth inhibitory activity, but only the diamides were adulticidal. Among neonicotinoids, acetamiprid had stronger ovicidal and adulticidal activity than thiamethoxam, showing within-insecticide class differences in toxicities; however, both were weak on larvae. Lethality of novaluron and indoxacarb was inconsistent, varying depending on species and stage. Chlorpyrifos was most toxic to O. insidiosus. These results show species- and stage-specific toxicities, and greater compatibility with biological control, of the newer reduced-risk classes of insecticides than older chemistries. PMID:27092527

  18. Toxicity of Insecticides on Various Life Stages of Two Tortricid Pests of Cranberries and on a Non-Target Predator.

    PubMed

    Rodriguez-Saona, Cesar; Wanumen, Andrea Carolina; Salamanca, Jordano; Holdcraft, Robert; Kyryczenko-Roth, Vera

    2016-01-01

    Laboratory and extended laboratory bioassays were conducted to determine the residual toxicities of various insecticides against two key pests of cranberries, Sparganothis sulfureana and Choristoneura parallela (Lepidoptera: Tortricidae), and their non-target effects on the predatory Orius insidiosus (Hemiptera: Anthocoridae). The effects of nine insecticides with different modes of action on S. sulfureana and Ch. parallela eggs, larvae, and adults were tested in the laboratory, while the efficacy of a post-bloom application on larval mortality and mass of these pests and on adult O. insidiosus was evaluated in extended laboratory experiments. The organophosphate chlorpyrifos and the spinosyn spinetoram provided long-lasting (seven-day) control against all stages of both pests. The growth regulator methoxyfenozide and the diamides chlorantraniliprole and cyantraniliprole had strong (1-7 days) larvicidal, particularly on young larvae, and growth inhibitory activity, but only the diamides were adulticidal. Among neonicotinoids, acetamiprid had stronger ovicidal and adulticidal activity than thiamethoxam, showing within-insecticide class differences in toxicities; however, both were weak on larvae. Lethality of novaluron and indoxacarb was inconsistent, varying depending on species and stage. Chlorpyrifos was most toxic to O. insidiosus. These results show species- and stage-specific toxicities, and greater compatibility with biological control, of the newer reduced-risk classes of insecticides than older chemistries. PMID:27092527

  19. Pyridalyl, a novel insecticide: potency and insecticidal selectivity.

    PubMed

    Isayama, S; Saito, S; Kuroda, K; Umeda, K; Kasamatsu, K

    2005-04-01

    Pyridalyl is an insecticide of a novel chemical class (unclassified insecticides). Toxicity of pyridalyl to two insect pest species, Spodoptera litura and Frankliniella occidentalis, an insect predator, Orius stringicollis, and a pollinator, Bombus terrestris, was evaluated in the laboratory. The insecticidal activity of pyridalyl against S. litura was evaluated using the leaf-dipping method. The potency of pyridalyl was highly effective against all development stages (2nd to 6th instar larvae) of S. litura. This compound was also evaluated against F. occidentalis using the direct spray method. For F. occidentalis, toxicity of pyridalyl was almost similar to that of acrinathrin, but greater than acrinathrin for adults. Then the toxicity of this product to the natural enemies, Orius stringicollis and the pollinating insect Bombus terrestris, was evaluated using the body-dipping method or direct spray method. No acute toxicity of this product was observed on these non-target insects. Moreover, the influence of pyridalyl to the nest of Bombus terrestris was evaluated using the direct spray to the inside of the nest. No apparent influence of this compound was observed by 21 days after treatment. The cytotoxicity of pyridalyl to the Sf9 insect cell line and the CHO-K1 mammalian cell line was evaluated using the trypan-blue exclusion method. High toxicity to the insect cell line, but almost no toxicity to the mammalian cell line, was observed. Thus, pyridalyl exhibited high selectivity in cytotoxicity between the insect and mammalian cell line as well as in insecticidal activity among insect species. We infer pyridalyl may be useful for IPM programs of greenhouse cultivation system. PMID:15756699

  20. The insecticide-resistance problem

    PubMed Central

    Brown, A. W. A.

    1958-01-01

    The author reviews the growth of the insecticide-resistance problem throughout the world during the period between July 1956 and November 1957, and the developments in research on the subject during the same period. Three new resistant species have been discovered—Anopheles subpictus, Chrysomyia putoria and Rhipicephalus sanguineus—and eight new types of resistance in already resistant species have been observed. Moreover, the geographical area covered by certain resistant insect populations has considerably increased. The research accomplishments during the period under review include: systems of detecting resistance in the field by standard test methods; confirmation of two distinct types of resistance to chlorinated-hydrocarbon insecticides in mosquitos and bed-bugs as well as in houseflies; evidence that DDT-resistance in the housefly, Anopheles sundaicus and Aëdes aegypti is due mainly to a single genetic factor associated with the ability to dehydrochlorinate DDT, and that dieldrin-resistance of Anopheles gambiae also derives from a single factor present even in untouched populations; a fuller understanding of the physiological mechanism of BHC-resistance in the housefly; and demonstration that selection pressure from organo-phosphorus compounds induces resistance to themselves and to chlorinated-hydrocarbon insecticides. PMID:13536795

  1. COMPARISON OF NEONICOTINOID INSECTICIDES WITH SILVERLEAF WHITEFLY INSECTICIDE STANDARDS FOR COTTON

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Silverleaf whitefly (SLW) insecticide efficacy research trials were conducted during the cotton seasons of 1997-2000 at the U of CA Desert Res. and Ext. Center in the Imperial Valley, CA to evaluate neonicotinoid insecticides and standard insecticides for control of SLW in cotton. Neonicotinoid inse...

  2. [Use of agricultural insecticides in Benin].

    PubMed

    Akogbeto, M C; Djouaka, R; Noukpo, H

    2005-12-01

    The use of insecticides in households and in agriculture has been incriminated in the emergence of insecticide resistance in insect vectors. For farming staff, the emergence of vector resistance is due to indoors spray of insecticides using aerosols and other low quality products in rural and urban settings against mosquitoes. On the other hand, public health specialists believe that the phenomenon of resistance could be due to massive use of insecticides in agriculture for field pests control. In Turkey, the implication of agricultural use of pesticides in the selection of vector resistance is clearly established. This study was framed to identify potential practices favouring the emergence of insecticide resistance in the Republic of Benin. Interviews and focus group discussions were organized with cotton, rice and vegetables farmers. The final aim of these surveys was to point out practices likely to favour the emergence of resistance. The research is conducted in 3 cotton fields, 2 rice fields and 2 vegetable plantations. After filling and signing concerned forms, farmers are subjected to quantitative and qualitative questionnaires to generate data on: insecticides being used, the various doses applied for pests eradication, the frequency of treatments, the cost of treatments (cost/hectare/year) the origin of insecticides, the place of purchase, safety precautions and related health hazards. The results of this study have shown that the use of insecticides in agriculture is a clear fact. During treatments, insecticide residues get in contact with mosquito breeding sites where they diffuse into water and exercise a selection pressure on larvae. This partially explains the high levels of resistance recorded in with strains of Anopheles gambiae collected in agricultural settings under insecticides pressure. Pyrethroids and more specifically deltamethrin and cyfluthrin are the insecticides mainly used in studied localities. Bedrooms of farmers are used as storage

  3. Re-Visiting Insecticide Resistance Status in Anopheles gambiae from Côte d'Ivoire: A Nation-Wide Informative Survey

    PubMed Central

    Koffi, Alphonsine A.; Ahoua Alou, Ludovic P.; Kabran, Jean-Paul K.; N'Guessan, Raphael; Pennetier, Cédric

    2013-01-01

    Insecticide resistance constitutes a major threat that may undermine current gain in malaria control in most endemic countries. National Malaria Control Programmes (NMCPs) need as much information as possible on the resistance status of malaria vectors and underlying mechanisms in order to implement the most relevant and efficient control strategy. Bioassays, biochemical and molecular analysis were performed on An. gambiae collected in six sentinel sites in Côte d'Ivoire. The sites were selected on the basis of their bioclimatic status and agricultural practices. An. gambiae populations across sites showed high levels of resistance to organochloride, pyrethroid and carbamate insecticides. The kdr and ace-1R mutations were detected in almost all sentinel sites with mosquitoes on the coastal and cotton growing areas mostly affected by these mutations. At almost all sites, the levels of detoxifying enzymes (mixed-function oxidases (MFOs), non-specific esterases (NSE) and glutathione-S-transferases (GSTs)) in An. gambiae populations were significantly higher than the levels found in the susceptible strain Kisumu. Pre-exposure of mosquitoes to PBO, an inhibitor of MFOs and NSEs, significantly increased mortality rates to pyrethroids and carbamates in mosquitoes but resistance in most cases was not fully synergised by PBO, inferring a residual role of additional mechanisms, including kdr and ace-1 site insensitivity. The large distribution of resistance in Côte d'Ivoire raises an important question of whether to continue to deploy pyrethroid-based long-lasting insecticidal nets (LLINs) and insecticide residual spraying (IRS) towards which resistance continues to rise with no guarantee that the level of resistance would not compromise their efficacy. Innovative strategies that combine insecticide and synergists in LLINs or spatially LLIN and an effective non-pyrethroid insecticide for IRS could be in the short term the best practice for the NMCP to manage insecticide

  4. Trifluoromethylphenyl amides as novel insecticides and fungicides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Because of increased resistance to insecticides in arthropods, it is necessary to identify new chemicals that may have novel modes of action. Following an extensive literature search for compounds with insecticidal and mosquito repellent activity, we have designed and synthesized a set of 20 trifluo...

  5. Insecticide Recommendations for Arkansas. MP 144.

    ERIC Educational Resources Information Center

    Jones, Bill F.; Barnes, Gordon

    This publication gives, in chart form, insecticides for use on animals, field crops, fruits, flowers, trees and shrubs, household pests, recreation areas, lawn and turf grass, pecans, stored grain, and vegetables. Included in the charts are the insecticides recommended for each insect, formulation to be used, amount, time to apply, and other…

  6. Trifluoromethylphenyl amides as novel insecticides and fungicides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Because of increased resistance to insecticides in arthropods, it is necessary to identify new chemicals that may have novel modes of action. Following an extensive literature search for compounds with insecticidal and mosquito repellent activity, we have designed and synthesized a set of 20 triflu...

  7. Trifluoromethylphenyl amides as novel insecticides and fungicides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Because of increased resistance to insecticides in arthropods, it is necessary to identify new chemicals that may have novel modes of action. Following an extensive literature search for compounds with insecticidal and mosquito repellent activity, we have designed and synthesized a set of 20 trif...

  8. Insecticidal compounds from Kalanchoe daigremontiana x tubiflora.

    PubMed

    Supratman, U; Fujita, T; Akiyama, K; Hayashi, H

    2001-09-01

    Methyl daigremonate, an insecticidal bufadienolide, was isolated from the leaves of Kalanchoe daigremontianaxtubiflora (Crassulaceae) along with four known bufadienolides. Its structure was established by spectroscopic analysis, and insecticidal activities were assessed against the third instar larvae of silkworm (Bombyx mori). The results suggest that the orthoester and alpha-pyrone moieties played an important role in the activity. PMID:11551556

  9. Insecticide Control of Vector-Borne Diseases: When Is Insecticide Resistance a Problem?

    PubMed Central

    Rivero, Ana; Vézilier, Julien; Weill, Mylène; Read, Andrew F.; Gandon, Sylvain

    2010-01-01

    Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way—and there may be no simple generality—the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention. PMID:20700451

  10. The insecticidal potential of venom peptides.

    PubMed

    Smith, Jennifer J; Herzig, Volker; King, Glenn F; Alewood, Paul F

    2013-10-01

    Pest insect species are a burden to humans as they destroy crops and serve as vectors for a wide range of diseases including malaria and dengue. Chemical insecticides are currently the dominant approach for combating these pests. However, the de-registration of key classes of chemical insecticides due to their perceived ecological and human health risks in combination with the development of insecticide resistance in many pest insect populations has created an urgent need for improved methods of insect pest control. The venoms of arthropod predators such as spiders and scorpions are a promising source of novel insecticidal peptides that often have different modes of action to extant chemical insecticides. These peptides have been optimized via a prey-predator arms race spanning hundreds of millions of years to target specific types of insect ion channels and receptors. Here we review the current literature on insecticidal venom peptides, with a particular focus on their structural and pharmacological diversity, and discuss their potential for deployment as insecticides. PMID:23525661

  11. Weevil x Insecticide: Does 'Personality' Matter?

    PubMed

    Morales, Juliana A; Cardoso, Danúbia G; Della Lucia, Terezinha Maria C; Guedes, Raul Narciso C

    2013-01-01

    An insect's behavior is the expression of its integrated physiology in response to external and internal stimuli, turning insect behavior into a potential determinant of insecticide exposure. Behavioral traits may therefore influence insecticide efficacy against insects, compromising the validity of standard bioassays of insecticide activity, which are fundamentally based on lethality alone. By extension, insect 'personality' (i.e., an individual's integrated set of behavioral tendencies that is inferred from multiple empirical measures) may also be an important determinant of insecticide exposure and activity. This has yet to be considered because the behavioral studies involving insects and insecticides focus on populations rather than on individuals. Even among studies of animal 'personality', the relative contributions of individual and population variation are usually neglected. Here, we assessed behavioral traits (within the categories: activity, boldness/shyness, and exploration/avoidance) of individuals from 15 populations of the maize weevil (Sitophilus zeamais), an important stored-grain pest with serious problems of insecticide resistance, and correlated the behavioral responses with the activity of the insecticide deltamethrin. This analysis was performed at both the population and individual levels. There was significant variation in weevil 'personality' among individuals and populations, but variation among individuals within populations accounted for most of the observed variation (92.57%). This result emphasizes the importance of individual variation in behavioral and 'personality' studies. When the behavioral traits assessed were correlated with median lethal time (LT50) at the population level and with the survival time under insecticide exposure, activity traits, particularly the distance walked, significantly increased survival time. Therefore, behavioral traits are important components of insecticide efficacy, and individual variation should be

  12. Hematological Disorders Following Exposure to Insecticides

    PubMed Central

    Mastromatteo, Ernest

    1964-01-01

    The medical literature dealing with hematological disorders following exposure to insecticides (chiefly chlorinated hydrocarbons and organic phosphorus compounds) is briefly reviewed. The development of blood dyscrasias as a consequence of exposure to insecticides is considered unlikely. Reported cases are few in number and often involve persons with little contact with these materials. It is often impossible to prove (or to disprove) a cause-and-effect relation in the individual case. Pointers which may be of assistance in evaluating this relationship are described. Purpura as a result of allergic vascular changes after exposure to insecticides is also discussed. PMID:14145471

  13. Fungal degradation of organophosphorous insecticides

    SciTech Connect

    Bumpus, J.A. ); Kakar, S.N.; Coleman, R.D. )

    1992-01-01

    Organophosphorous insecticides are used extensively to treat a variety of pests and insects. Although as a group they are easily degraded by bacteria in the environment, a number of them have half-lives of several months. Little is known about their biodegradation by fungi. We have shown that Phanerochaete chrysosporium can substantially degrade chlorpyrifos, fonofos, and terbufos (27.5%, 12.2%, and 26.6%, respectively) during 18-day incubation in nitrogen-limited stationary cultures. The results demonstrate that the clorinated pyridinyl ring of chlorpyrifos and the phenyl ring of fonofos undergo ring cleavage during biodegradation by the fungus. The usefulness of the fungus system for bioremediation is discussed. 16 refs., 7 figs., 2 tabs.

  14. [Preliminary evaluation of the insecticide susceptibility in Anopheles gambiae and Culex quinquefasciatus from Lobito (Angola), using WHO standard assay].

    PubMed

    Toto, J C; Besnard, P; Le Mire, J; Almeida, D S I; Dos Santos, M A; Fortes, F; Foumane, V; Simard, F; Awono-Ambene, H P; Carnevale, P

    2011-10-01

    Field collections of the most common urban mosquito vectors Anopheles gambiae and Culex quinquefasciatus were carried out in June 2003, March 2004 and November 2005 to gather preliminary data on the insecticide susceptibility in mosquitoes from Lobito (Angola) using the WHO standard bioassays. Bioassays were performed on F0 adults emerging from the field larval collections and on unfed adults from landing catches on volunteers. Batches of mosquitoes from three selected locations (Alto Liro, San Jao and Bela Vista) were exposed for 1 hour to several insecticides such as DDT 4%, carbosulfan 0.4%, permethrin 1%, deltamethrin 0.05% and cyfluthrin 0.15%, in order to estimate the immediate knockdown times (kdT50 and kdT95) and the mortality rate after exposure. The results revealed that mosquito susceptibility to insecticides varied depending on the insecticide, the site and the period of collection. The main local malaria vector A. gambiae (both M and S forms) was basically resistant to DDT and susceptible to all pyrethoids, regardless of the period and the site of collections. The overall mortality rate due to DDT was 73% in Alto Liro, 89% in San Jao and varied depending on the period in Bela Vista between 95% in March 2004 and 100% in November 2005. The mortality due to pyrethoids was 100% at all locations, with the kdT50 and KdT95 times ranging between 9 and 16 minutes and between 18 and 29 minutes, respectively. Concerning the C. quinquefasciatus, populations from Yard and Caponte were resistant to all insecticides tested; the mortality rate was 40% with deltamethrin and 70% with permethrin, while no lethal effect was observed with DDT or carbosulfan. In conclusion, despite its probable high resistance to DDT, the main local malaria vector A. gambiae remained fully susceptible to pyrethroids. This could forecast a good biological efficacy of the scheduled vector control interventions in Angola, based on a large-scale distribution of long-lasting, insecticide

  15. Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages.

    PubMed

    Moretti, Sarah; Franchi, Silvia; Castelli, Mara; Amodeo, Giada; Somaini, Lorenzo; Panerai, Alberto; Sacerdote, Paola

    2015-06-01

    Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC did not affect brain cytokines in adult mice, but a proinflammatory cytokine decrease was evident in the adolescent brain. A similar effect was present in the hypothalamus and hippocampus after 10 days' THC administration. In contrast, when brain cytokines were measured 47 days after the final THC administration, we observed an inverted effect in adult mice treated as adolescents, i.e., IL-1β and TNF-α increased and IL-10 decreased, indicating a shift toward neuroinflammation. These data suggest that THC exposure in adolescence has long-lasting effects on brain cytokines that parallel those present in the periphery. This modulation may affect vulnerability to immune and behavioural diseases in adulthood. PMID:25875136

  16. Insecticidal sugar baits for adult biting midges.

    PubMed

    Snyder, D; Cernicchiaro, N; Allan, S A; Cohnstaedt, L W

    2016-06-01

    The mixing of an insecticide with sugar solution creates an oral toxin or insecticidal sugar bait (ISB) useful for reducing adult insect populations. The ability of ISBs to kill the biting midge Culicoides sonorensis Wirth and Jones (Diptera: Ceratopogonidae), a vector of bluetongue virus, epizootic hemorrhagic disease and vesicular stomatitis viruses, was tested. The commercial insecticide formulations (percentage active ingredient) tested included bifenthrin, cyfluthrin, deltamethrin, permethrin, dinotefuran, imidacloprid, thiamethoxam and spinosad. Mortality rates were determined for various concentrations of commercial formulations (0.01, 0.05, 0.1, 1, 2 and 3%) and observed at 1, 4, 10 and 24 h post-exposure to the ISB. In the first set of assays, laboratory-reared midges were fed sugar ad libitum and then exposed to insecticide-treated sugar solutions to measure mortality. The second assay assessed competitive feeding: midges were provided with a control sugar solution (10% sucrose) in one vial, and a sugar and insecticide solution in another. Pyrethroid treatments resulted in the greatest mortality in the first hour at the lowest concentrations and spinosad consumption resulted in the least mortality. Biting midges were not deterred from feeding on the 1% ISB solutions despite the presence of an insecticide-free alternative source of sugar. PMID:26789534

  17. Impact of insecticides on the invasive Halyomorpha halys (Hemiptera: Pentatomidae): analysis of insecticide lethality.

    PubMed

    Leskey, Tracy C; Lee, Doo-Hyung; Short, Brent D; Wright, Starker E

    2012-10-01

    The efficacy of 37 insecticide treatments against adult Halyomorpha halys (Stål) was established based on exposure to 18-h old dry insecticide residue in laboratory bioassays. Individual adult H. halys were exposed to an insecticide residue for 4.5 h and then monitored daily for survivorship over a 7-d period. The proportion of dead and moribund insects was used as an estimate of overall insecticide efficacy against H. halys immediately after the exposure period and over the 7-d trial. Among all materials evaluated, 14 insecticides exhibited increasing efficacy, in which the percentage of dead and moribund insects (used as a measure of insecticide efficacy) increased by > 10% after 7 d. By contrast, insecticide efficacy values of eight insecticides declined by > 10% (based on recovery of adults from a moribund state) over the 7-d period with most belonging to the pyrethroid class. In this study, the efficacy value of neonicotinoid, acetamiprid, showed the greatest decline from 93 to 10% over 7 d. A lethality index (scale of 0-100) was developed to compare insecticides based on quantifying the immediate and longer-term effects of insecticide exposure on H. halys. Among all materials evaluated, dimethoate, malathion, bifenthrin, methidathion, endosulfan, methomyl, chlorpyrifos, acephate, fenpropathrin, and permethrin yielded the highest values (> 75) because of a high degree of immediate mortality with very little recovery. Our results provide baseline information regarding potential of candidate insecticides against adult H. halys and highlight the need to consider longer-term effects in establishing overall efficacy ratings against this invasive species. PMID:23156170

  18. Modeling global distribution of agricultural insecticides in surface waters.

    PubMed

    Ippolito, Alessio; Kattwinkel, Mira; Rasmussen, Jes J; Schäfer, Ralf B; Fornaroli, Riccardo; Liess, Matthias

    2015-03-01

    Agricultural insecticides constitute a major driver of animal biodiversity loss in freshwater ecosystems. However, the global extent of their effects and the spatial extent of exposure remain largely unknown. We applied a spatially explicit model to estimate the potential for agricultural insecticide runoff into streams. Water bodies within 40% of the global land surface were at risk of insecticide runoff. We separated the influence of natural factors and variables under human control determining insecticide runoff. In the northern hemisphere, insecticide runoff presented a latitudinal gradient mainly driven by insecticide application rate; in the southern hemisphere, a combination of daily rainfall intensity, terrain slope, agricultural intensity and insecticide application rate determined the process. The model predicted the upper limit of observed insecticide exposure measured in water bodies (n = 82) in five different countries reasonably well. The study provides a global map of hotspots for insecticide contamination guiding future freshwater management and conservation efforts. PMID:25555206

  19. Sol–gel synthesis of long-lasting phosphors CdSiO{sub 3}: Mn{sup 2+}, RE{sup 3+} (RE = Tb, Eu, Nd) and luminescence mechanism research

    SciTech Connect

    Qu, Xiaofei; Cao, Lixin; Liu, Wei; Su, Ge; Wang, Pingping; Schultz, Isabel

    2012-06-15

    Highlights: ► New long-lasting CdSiO{sub 3}: Mn{sup 2+}, RE{sup 3+} (RE = Tb, Eu, Nd) phosphors were synthesized by a sol–gel method. ► The afterglow performance of the CdSiO{sub 3}: Mn{sup 2+}, Eu{sup 3+} phosphor was the best. ► The role of RE{sup 3+} co-doped into the CdSiO{sub 3}: Mn{sup 2+} matrix was discussed in this paper. -- Abstract: Mn{sup 2+} and RE{sup 3+} (RE = Tb, Eu, Nd) co-doped CdSiO{sub 3} orange phosphors were prepared at 1050 °C by a sol–gel method. The phase and crystallinity of the synthesized materials were investigated by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The luminescence characteristics were analyzed using photoluminescence (PL) spectra, afterglow decay curves, long-lasting phosphorescence spectra, and thermoluminescence (TL) spectra. Due to the difference in co-doped rare earth ionic radii, it varied greatly in trap density and trap depth caused by the different defects deriving from RE{sup 3+} ions co-doping into the CdSiO{sub 3}: Mn{sup 2+} host. The afterglow intensity and time for these samples increased as follows: CdSiO{sub 3}: Mn{sup 2+}0.2%, Nd{sup 3+}0.8% < CdSiO{sub 3}: Mn{sup 2+}0.4%, Tb{sup 3+}0.8% < CdSiO{sub 3}: Mn{sup 2+}0.4%, Eu{sup 3+}0.3%. CdSiO{sub 3}: Mn{sup 2+}0.4%, Eu{sup 3+}0.3% had the best afterglow properties, which could be due to the proper traps formed by Eu{sup 3+} ions co-doping into the host. The role of RE{sup 3+} co-doped into the CdSiO{sub 3}: Mn{sup 2+} matrix and the possible long-lasting phosphorescence process was also discussed in this paper.

  20. THE INTERACTION OF AN ANTICHOLINESTERASE INSECTICIDE, DIAZINON, WITH A PYRETHROID INSECTICIDE, DELTAMETHRIN.

    EPA Science Inventory

    This present study explores the interaction of the toxicity induced by an organophosphorus insecticide, diazinon (diethyl 2-isopropyl-6methyl-4-pyrimidal phosphorothionate), with a pyrethroid insecticide, deltamethrin ((S)-a-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dibromovinyl)-2,...

  1. THE ANTICHOLINESTERASE INSECTICIDE, DIAZINON, MAY POTENTIATE THE TOXICITY OF THE PYRETHROID INSECTICIDE DELTAMETHRIN AT LOW DOSAGES.

    EPA Science Inventory

    This present study explores the interaction of the toxicity induced by an organophosphorus insecticide, diazinon (diethyl 2-isopropyl-6methyl-4-pyrimidal phosphorothionate), with a pyrethroid insecticide, deltamethrin ((S)-a-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dibromovinyl)-2,...

  2. Toxicity of selected insecticides and insecticide mixtures to adult brown stink bug (Heteroptera: Pentatomidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glass vial bioassay were conducted to evaluate the toxicity of selected insecticides and insecticide mixtures to the brown stink bug (BSB), Euschistus servus (Say) collected from blacklight traps, cotton plants and weeds in farming areas in the Brazos Valley of Texas. Dicrotophos was 5- and 18-fold...

  3. Pyrethroid insecticides in municipal wastewater.

    PubMed

    Weston, Donald P; Ramil, Heather L; Lydy, Michael J

    2013-11-01

    Pyrethroids are widely used insecticides, but minimal information has been published on their presence in municipal wastewater in the United States. Pyrethroids in wastewater from the Sacramento, California, USA, area consisted of permethrin, bifenthrin, cypermethrin, and cyhalothrin, with a combined concentration of 200 ng/L to 500 ng/L. Sampling within the wastewater collection system leading to the treatment plant suggested pyrethroids did not originate primarily from urban runoff, but could be from any of several drain disposal practices. Wastewater from residential areas was similar in pyrethroid composition and concentration to that from the larger metropolitan area as a whole. Secondary treatment removed approximately 90% of pyrethroids, but those remaining exceeded concentrations acutely toxic to sensitive species. Toxicity to the amphipod, Hyalella azteca, was consistently evident in the final effluent. The large river into which this particular plant discharged provided sufficient dilution such that pyrethroids were undetected in the river, and there was only slight toxicity of unknown cause in 1 river sample, but effects in receiving waters elsewhere will be site-specific. PMID:23893650

  4. Decreased CD127 Expression on CD4+ T-Cells and Elevated Frequencies of CD4+CD25+CD127− T-Cells in Children with Long-Lasting Type 1 Diabetes

    PubMed Central

    Glowinska-Olszewska, Barbara; Rusak, Malgorzata; Jeznach, Marta; Grubczak, Kamil; Lipinska, Danuta; Milewska, Anna Justyna; Dabrowska, Milena; Jablonska, Ewa; Kretowski, Adam; Gorska, Maria; Bodzenta-Lukaszyk, Anna; Bossowski, Artur

    2013-01-01

    Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127− phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127− T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127− T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25− T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127− T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype. PMID:24348676

  5. Insecticide susceptibility of Cnaphalocrocis medinalis (Lepidoptera: Pyralidae) in China.

    PubMed

    Zheng, Xuesong; Ren, Xiubei; Su, Jianya

    2011-04-01

    Insecticide control is the major measure for suppression of Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae) damage, and a few insecticides used for long time have proved to fail to control this pest in China. Several new chemicals have been introduced for control of C. medinalis. However, there was no baseline susceptibility data of C. medinalis to insecticides used or will be in use. In this study, a seedling dipping method was developed for bioassay of insecticide susceptibility of C. medinalis. Dose responses of C. medinalis to 11 insecticides were tested. Interpopulation sensitivity to insecticides was compared. Based on LC50 values, C. medinalis was most susceptible to antibiotic insecticides (abamectin, emamectin benzoate, and spinosad) and least sensitive to monosultap and a Bacillus thuringiensis (Bt) product. Chlorantraniliprole and insect growth regulator (IGR) insecticides (tebufenozide and hexaflumuron) exhibited great efficacy against C. medinalis. No susceptibility difference was observed for antibiotic insecticide and IGR insecticides among three populations. Narrow variation in tolerant level was detected for organophosphates insecticides, chlorantraniliprole, monosultap, and Bt. The results in this study provided baseline susceptibility data of C. medinalis to 11 insecticides and also offered useful information for choice of alternative insecticide and for integrated resistance management of C. medinalis. PMID:21510218

  6. Design, synthesis and bioassay of new mosquito insecticides and repellents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New compounds and classes of compounds are needed to protect deployed military personnel from diseases transmitted by medically important arthropods. Historically, the synthetic insecticides and repellents have been effective tools for mosquito control. To develop new synthetic insecticides and repe...

  7. Residual insecticides and the problem of sorption

    PubMed Central

    Bertagna, P.

    1959-01-01

    Whereas laboratory investigations have elucidated the mechanism of sorption of residual insecticides and demonstrated that their persistency is determined by a number of physico-chemical factors and is therefore theoretically calculable, the variables encountered in the field may produce results in apparent conflict with those theoretically expected. Attempts to enhance persistency through the prevention of sorption, although promising, have so far not been fully successful. It is consequently also necessary to assess the residual effectiveness of insecticides, “effectiveness” here being viewed as a biological effect expressed in terms of the mosquito mortality produced. For this purpose bio-assay tests have been used, but with very variable results, and it is suggested that a study of the bio-assay technique itself is needed. This should be conducted in parallel with chemical determinations of the total amount of insecticide present both on and below the sprayed surface. PMID:13799942

  8. Inhibition of aflatoxin production by selected insecticides.

    PubMed

    Draughon, F A; Ayres, J C

    1981-04-01

    The insecticide naled completed inhibition production of aflatoxins B1, B2, G1, and G2 by and growth of Aspergillus parasiticus at a 100-ppm (100 microgram/ml) concentration. The insecticides dichlorvos, Landrin, pyrethrum, Sevin, malathion, and Diazinon significantly (P = 0.05) inhibited production of aflatoxins at a 100-ppm concentration. However, at a concentration of 10 ppm, significant inhibition in production of aflatoxins was found only with naled, dichlorvos, Sevin, Landrin, and pyrethrum. Dichlorvos, Landrin, Sevin, and naled inhibited growth of A. parasiticus by 28.9 , 18.9, 15.7, and 100%, respectively, at 100 ppm. Stimulation of growth was observed when diazinon was added to cultures. Aflatoxin B1 was most resistant to inhibition by insecticides, followed by G1, G2, and B2, respectively. PMID:6786222

  9. Structure—activity relationships for insecticidal carbamates*

    PubMed Central

    Metcalf, Robert L.

    1971-01-01

    Carbamate insecticides are biologically active because of their structural complementarity to the active site of acetylcholinesterase (AChE) and their consequent action as substrates with very low turnover numbers. Carbamates behave as synthetic neurohormones that produce their toxic action by interrupting the normal action of AChE so that acetylcholine accumulates at synaptic junctions. The necessary properties for a suitable insecticidal carbamate are lipid solubility, suitable structural complementarity to AChE, and sufficient stability to multifunction-oxidase detoxification. The relationships between the structure and the activity of a large number of synthetic carbamates are analysed in detail, with particular attention to the second of these properties. PMID:5315358

  10. Polyimide nanofoams from aliphatic polyester based copolymers

    SciTech Connect

    Hedrick, J.L.; Carter, K.R.; Richter, R.; Russell, T.P.

    1996-10-01

    High temperature polymer foams were prepared using microphase separated block copolymers where the major component is thermally stable block and the minor component is thermally labile. Upon thermal treatment, the dispersed minor component undergoes thermolysis leaving pores the size and shape of which are dictated by the initial copolymer morphology. The driving force behind the survey of aliphatic polyesters as possible labile blocks stems from their quantitative degradation into low boiling, polar degradation products via a backbiting process. Block copolymers were prepared using either a monofunctional caprolactone or a valerolactone oligomer and a high T. polyimide. Microphase morphologies were observed in each case. Thermal decomposition of the polyester blocks was accomplished by a thermal treatment at 370{degrees}C for 5 h. Significant density reductions were measured, and the resulting foams showed pore sizes in the 60-70 {Angstrom} range.

  11. Multicentre studies of insecticide-treated durable wall lining in Africa and South-East Asia: entomological efficacy and household acceptability during one year of field use

    PubMed Central

    2012-01-01

    Background Indoor residual spraying (IRS) is a primary method of malaria vector control, but its potential impact is constrained by several inherent limitations: spraying must be repeated when insecticide residues decay, householders can tire of the annual imposition and campaign costs are recurrent. Durable lining (DL) can be considered an advanced form of long-lasting IRS where insecticide is gradually released from an aesthetically attractive wall lining material to provide vector control for several years. A multicentre trial was carried out in Equatorial Guinea, Ghana, Mali, South Africa and Vietnam to assess the feasibility, durability, bioefficacy and household acceptability of DL, compared to conventional IRS or insecticide-treated curtains (LLITCs), in a variety of operational settings. Methods This study was conducted in 220 households in traditional rural villages over 12-15 months. In all sites, rolls of DL were cut to fit house dimensions and fixed to interior wall surfaces (usually with nails and caps) by trained teams. Acceptability was assessed using a standardized questionnaire covering such topics as installation, exposure reactions, entomology, indoor environment, aesthetics and durability. Bioefficacy of interventions was evaluated using WHO cone bioassay tests at regular intervals throughout the year. Results The deltamethrin DL demonstrated little to no decline in bioefficacy over 12-15 months, supported by minimal loss of insecticide content. By contrast, IRS displayed a significant decrease in bioactivity by 6 months and full loss after 12 months. The majority of participants in DL households perceived reductions in mosquito density (93%) and biting (82%), but no changes in indoor temperature (83%). Among those households that wanted to retain the DL, 73% cited protective reasons, 20% expressed a desire to keep theirs for decoration and 7% valued both qualities equally. In Equatorial Guinea, when offered a choice of vector control product at

  12. The development of insecticide-treated durable wall lining for malaria control: insights from rural and urban populations in Angola and Nigeria

    PubMed Central

    2012-01-01

    Background Durable lining (DL) is a deltamethrin-impregnated polyethylene material, which is designed to cover domestic walls that would normally be sprayed with residual insecticide. The operational success of DL as a long-lasting insecticidal substrate will be dependent on a high level of user acceptability as households must maintain correctly installed linings on their walls for several years. Preliminary trials were undertaken to identify a material to develop into a marketable wall lining and to assess its level of acceptability among rural and urban populations. Methods In Angola (n=60), prototype DL and insecticide-treated plastic sheeting (ITPS) were installed on urban house walls and ceilings, respectively, and acceptability was compared to indoor residual spraying (IRS) (n=20) using a knowledge, attitude and practice (KAP) questionnaire. In Nigeria (n=178), three materials (prototype DL, ITPS and insecticide-treated wall netting) were distributed among rural and urban households. User opinions were gathered from focus group discussions, in-depth interviews and KAP questionnaires. Results In Angola, after two weeks, the majority of participants (98%) expressed satisfaction with the products and identified the killing of insects as the materials’ principal benefits (73%). After one year, despite a loss of almost 50% of households to refugee repatriation, all 32 remaining households still asserted that they had liked the DL/ITPS in their homes and given the choice of intervention preferred DL/ITPS to IRS (94%) or insecticide-treated nets (78%). In Nigeria, a dichotomy between rural and urban respondents emerged. Rural participants favoured wall adornments and accepted wall linings because of their perceived decorative value and entomological efficacy. By contrast, urban households preferred minimal wall decoration and rejected the materials based upon objections to their aesthetics and installation feasibility. Conclusions The high level of acceptability

  13. Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line

    NASA Astrophysics Data System (ADS)

    Yang, Chengbin; Panwar, Nishtha; Wang, Yucheng; Zhang, Butian; Liu, Maixian; Toh, Huiting; Yoon, Ho Sup; Tjin, Swee Chuan; Chong, Peter Han Joo; Law, Wing-Cheung; Chen, Chih-Kuang; Yong, Ken-Tye

    2016-04-01

    First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro

  14. Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line.

    PubMed

    Yang, Chengbin; Panwar, Nishtha; Wang, Yucheng; Zhang, Butian; Liu, Maixian; Toh, Huiting; Yoon, Ho Sup; Tjin, Swee Chuan; Chong, Peter Han Joo; Law, Wing-Cheung; Chen, Chih-Kuang; Yong, Ken-Tye

    2016-04-28

    First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro

  15. Impact of insecticides on the invasive Halyomorpha halys (Stal) (Hemiptera:Pentatomidae): analysis on the insecticide lethality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of 37 insecticides against adult Halyomorpha halys (Stal) was established based on exposure to 18-h old dry insecticide residue in laboratory bioassays. Adult H. halys were exposed to an insecticide residue for 4.5 h and then monitored daily for survivorship over a 7-d period. The pro...

  16. A genetic model of the effects of insecticide-treated bed nets on the evolution of insecticide-resistance

    PubMed Central

    Birget, Philip L. G.; Koella, Jacob C.

    2015-01-01

    Background and objectives: The evolution of insecticide-resistance in malaria vectors is emerging as a serious challenge for the control of malaria. Modelling the spread of insecticide-resistance is an essential tool to understand the evolutionary pressures and dynamics caused by the application of insecticides. Methodology: We developed a population-genetic model of the spread of insecticide-resistance in a population of Anopheles vectors in response to insecticides used either as adulticides (focussing on insecticide-treated bed nets (ITNs)) or as larvicides (either for the control of malaria or, as an inadvertent side-product, in agriculture). Results: We show that indoor use of insecticides leads to considerably less selection pressure than their use as larvicides, supporting the idea that most resistance of malaria vectors is due to the agricultural use of the insecticides that are also used for malaria control. The reasons for the relatively low selection pressure posed by adulticides are (i) that males are not affected by the ITNs and, in particular, (ii) that the insecticides are also repellents, keeping mosquitoes at bay from contacting the insecticide but also driving them to bite either people who do not use the insecticide or alternative hosts. Conclusion: We conclude by discussing the opposing public health benefits of high repellency at an epidemiological and an evolutionary timescale: whereas repellency is beneficial to delay the evolution of resistance, other models have shown that it decreases the population-level protection of the insecticide. PMID:26320183

  17. Long lasting sex-specific effects upon behavior and S100b levels after maternal separation and exposure to a model of post-traumatic stress disorder in rats.

    PubMed

    Diehl, Luisa Amalia; Silveira, Patrícia Pelufo; Leite, Marina C; Crema, Leonardo Machado; Portella, Andre Krumel; Billodre, Mauro Nör; Nunes, Edelvan; Henriques, Thiago P; Fidelix-da-Silva, Linda Brenda; Heis, Marta D; Gonçalves, Carlos Alberto; Quillfeldt, Jorge Alberto; Dalmaz, Carla

    2007-05-01

    This study was undertaken to verify if repeated long-term separation from dams would affect the development of parameters related to post-traumatic stress disorder (PTSD) after animals are subjected to inescapable shock when adults. Wistar rats were subjected to repeated maternal separation during post-natal days 1-10. When adults, rats from both sexes were submitted to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. We observed long-lasting effects of both interventions. Exposure to shock increased fear conditioning. Anxiety-like behavior was increased and exploratory activity decreased by both treatments, and these effects were more robust in males. Additionally, basal corticosterone in plasma was decreased, paralleling effects observed in PTSD patients. Levels of S100B protein in serum and cerebrospinal fluid (CSF) were measured. Levels in serum correlated with the effects observed in anxiety-like behavior, increasing in males exposed to shock, and presenting no effect in females. S100B in CSF was increased in females submitted to maternal separation during the neonatal period. These results suggest that, in rats, an early stress experience such as maternal separation may aggravate some effects of exposure to a stressor during adult age, and that this effect is sex-specific. Additionally, data suggest that the increased S100B levels, observed in serum, have an extracerebral origin, possibly mediated by an increase in the noradrenergic tonus. Increased S100B in brain could be related to its neurotrophic actions. PMID:17335785

  18. Optical study of SrAl 1.7B 0.3O 4:Eu, R ( R=Nd, Dy) pigments with long-lasting phosphorescence for industrial uses

    NASA Astrophysics Data System (ADS)

    Sánchez-Benítez, J.; de Andrés, A.; Marchal, M.; Cordoncillo, E.; Regi, M. Vallet; Escribano, P.

    2003-02-01

    We have studied and compared the optical properties of SrAl 1.7B 0.3O 4:Eu, R ( R=Nd, Dy) pigments that present long-lasting phosphorescence obtained by different synthesis techniques. Samples obtained by ceramic methods, in our laboratories and by an industrial process, present better phosphorescent properties than those obtained by sol-gel technique. Raman spectra show that grinding produces severe damage of the lattice. We have obtained and analyzed the Eu 3+ crystal field luminescence indicating that Eu 3+ is found in quite different sites comparing ceramic and sol-gel samples. Codoping, with Nd or Dy is necessary in order to reduce the Eu 3+ content, in all cases. The green luminescence band, obtained under UV illumination, can be fitted to two and three components in ceramic and sol-gel samples, respectively, due to different Eu 2+ sites. Eu-Dy samples present the longest and the most efficient phosphorescence. The time evolution of the afterglow is well described by a t-1 law, up to about 2 h, indicating that the recombination process is achieved by electron-hole tunneling.

  19. White long-lasting phosphorescence generation in a CaAl2Si2O8 : Eu2+, Mn2+, Dy3+ system through persistent energy transfer

    NASA Astrophysics Data System (ADS)

    Zhang, Jinsu; Chen, Baojiu; Sun, Jiashi; Li, Xiangping; Cheng, Lihong; Zhong, Haiyang

    2012-08-01

    Based on the persistent energy transfer principle, Mn2+ was introduced into a CaAl2Si2O8 : Eu2+/Dy3+ phosphor to achieve white long-lasting emissions. Eu2+, Mn2+ and Dy3+ tri-doped CaAl2Si2O8 phosphors with various Mn2+ concentrations were prepared via a solid-state reaction, and the crystal structure of the phosphors was identified by the x-ray diffraction technique. The luminescent properties of the Eu2+, Mn2+ and Dy3+ tri-doped CaAl2Si2O8 phosphors were studied. The energy transfer behaviour from Eu2+ to Mn2+ was analysed within the framework of Dexter theory. The physical mechanism of energy transfer was assigned to the electric dipole-quadrupole interaction. It was also demonstrated that the colour coordinates of the phosphors can be tuned from the blue region to the white region in the colour space. Furthermore, the afterglow decay and thermoluminescence curves were measured, indicating excellent phosphorescence properties of the current phosphors.

  20. Pituitary adenylate cyclase-activating peptide induces long-lasting neuroprotection through the induction of activity-dependent signaling via the cyclic AMP response element-binding protein-regulated transcription co-activator 1

    PubMed Central

    Baxter, Paul S; Martel, Marc-Andre; McMahon, Aoife; Kind, Peter C; Hardingham, Giles E

    2011-01-01

    Pituitary adenylate cyclase-activating peptide (PACAP) is a neuroprotective peptide which exerts its effects mainly through the cAMP-protein kinase A (PKA) pathway. Here, we show that in cortical neurons, PACAP-induced PKA signaling exerts a major part of its neuroprotective effects indirectly, by triggering action potential (AP) firing. Treatment of cortical neurons with PACAP induces a rapid and sustained PKA-dependent increase in AP firing and associated intracellular Ca2+ transients, which are essential for the anti-apoptotic actions of PACAP. Transient exposure to PACAP induces long-lasting neuroprotection in the face of apoptotic insults which is reliant on AP firing and the activation of cAMP response element (CRE) binding protein (CREB)-mediated gene expression. Although direct, activity-independent PKA signaling is sufficient to trigger phosphorylation on CREB’s activating serine-133 site, this is insufficient for activation of CREB-mediated gene expression. Full activation is dependent on CREB-regulated transcription co-activator 1 (CRTC1), whose PACAP-induced nuclear import is dependent on firing activity-dependent calcineurin signaling. Over-expression of CRTC1 is sufficient to rescue PACAP-induced CRE-mediated gene expression in the face of activity-blockade, while dominant negative CRTC1 interferes with PACAP-induced, CREB-mediated neuroprotection. Thus, the enhancement of AP firing may play a significant role in the neuroprotective actions of PACAP and other adenylate cyclase-coupled ligands. PMID:21623792

  1. Report on the second WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Geneva, Switzerland, 5-7 May 2014.

    PubMed

    Cox, Nancy J; Hickling, Julian; Jones, Rebecca; Rimmelzwaan, Guus F; Lambert, Linda C; Boslego, John; Rudenko, Larisa; Yeolekar, Leena; Robertson, James S; Hombach, Joachim; Ortiz, Justin R

    2015-11-27

    On 5-7 May 2014, the World Health Organization (WHO) convened the second integrated meeting on "influenza vaccines that induce broadly protective and long-lasting immune responses". Around 100 invited experts from academia, the vaccine industry, research and development funders, and regulatory and public health agencies attended the meeting. Areas covered included mechanisms of protection in natural influenza-virus infection and vaccine-induced immunity, new approaches to influenza-vaccine design and production, and novel routes of vaccine administration. A timely focus was on how this knowledge could be applied to both seasonal influenza and emerging viruses with pandemic potential such as influenza A (H7N9), currently circulating in China. Special attention was given to the development of possible universal influenza vaccines, given that the Global Vaccine Action Plan calls for at least one licensed universal influenza vaccine by 2020. This report highlights some of the topics discussed and provides an update on studies published since the report of the previous meeting. PMID:26478203

  2. Insecticide Resistance: Challenge to Pest Management and Basic Research

    NASA Astrophysics Data System (ADS)

    Brattsten, L. B.; Holyoke, C. W.; Leeper, J. R.; Raffa, K. F.

    1986-03-01

    The agricultural use of synthetic insecticides usually protects crops but imposes strong selection pressures that can result in the development of resistance. The most important resistance mechanisms are enhancement of the capacity to metabolically detoxify insecticides and alterations in target sites that prevent insecticides from binding to them. Insect control methods must incorporate strategies to minimize resistance development and preserve the utility of the insecticides. The most promising approach, integrated pest management, includes the use of chemical insecticides in combination with improved cultural and biologically based techniques.

  3. DEVELOPMENTAL NEUROTOXICITY OF PYRETHROID INSECTICIDES: CRITICAL REVIEW.

    EPA Science Inventory

    Pyrethroids are widely utilized insecticides whose primary action is the disruption of voltage-sensitive sodium channels (VSSC). Although these compounds have been in use for over 30 years and their acute neurotoxicity has been well characterized, there is considerably less info...

  4. Insecticidal sugar baits for adult biting midges

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the latest trends in mosquito control is the use of insecticidal sugar baits (ISBs) to reduce adult mosquito populations. Tested here is the ability of ISB’s to knock-down the biting midge, Culicoides sonorensis, a disease vector of bluetongue, epizootic hemorrhagic disease, and vesicular sto...

  5. The 1975 Insecticide, Herbicide, Fungicide Quick Guide.

    ERIC Educational Resources Information Center

    Page, Bill G.; Thomson, W. T.

    This is a quick guide for choosing a chemical to use to control a certain pest on a specific crop. Information in the book was obtained from manufacturers' labels and from the USDA and FDA pesticide summary. The book is divided into four parts: (1) insecticides, (2) herbicides, (3) fungicides, and (4) conversion tables. Each of the first three…

  6. COMPARATIVE TOXICOLOGY OF THE PYRETHROID INSECTICIDES

    EPA Science Inventory

    Synthetic pyrethroid insecticides are photostable analogs of the natural pyrethrins of botanical origin. heir structures range from very similar to the original (e.g., allethrin, Fig. 1) to highly dissimilar compounds (e.g., flucythrinate, Fig. 1). irected synthesis by groups in ...

  7. Insecticide-induced hormesis and arthropod pest management.

    PubMed

    Guedes, Raul Narciso C; Cutler, G Christopher

    2014-05-01

    Ecological backlashes such as insecticide resistance, resurgence and secondary pest outbreaks are frequent problems associated with insecticide use against arthropod pest species. The last two have been particularly important in sparking interest in the phenomenon of insecticide-induced hormesis within entomology and acarology. Hormesis describes a biphasic dose-response relationship that is characterized by a reversal of response between low and high doses of a stressor (e.g. insecticides). Although the concept of insecticide-induced hormesis often does not receive sufficient attention, or has been subject to semantic confusion, it has been reported in many arthropod pest species and natural enemies, and has been linked to pest outbreaks and potential problems with insecticide resistance. The study of hormesis remains largely neglected in entomology and acarology. Here, we examined the concept of insecticide-induced hormesis in arthropods, its functional basis and potential fitness consequences, and its importance in arthropod pest management and other areas. PMID:24155227

  8. Specific time of exposure during tadpole development influences biological effects of the insecticide carbaryl in green frogs (Lithobates clamitans).

    PubMed

    Boone, Michelle D; Hammond, S Austin; Veldhoen, Nik; Youngquist, Melissa; Helbing, Caren C

    2013-04-15

    The orchestration of anuran metamorphosis is initiated and integrated by thyroid hormones, which change dynamically during larval development and which may represent a target of disruption by environmental contaminants. Studies have found that some anurans experience increased rates of development when exposed to the insecticide carbaryl later in larval development, suggesting that this insecticide could affect thyroid hormone-associated biological pathways. However, the time in development when tadpoles are sensitive to insecticide exposure has not been clearly defined nor has the mechanism been tested. In two separate studies, we exposed recently hatched green frog (Lithobates clamitans) tadpoles to a single, three day carbaryl exposure in the laboratory at either 2, 4, 8, or 16 weeks post-hatching. We examined the impact of carbaryl exposure on mRNA abundance patterns in the brains of frogs following metamorphosis months after a single three day exposure (experiment 1) and in tadpole tails three days after exposure (experiment 2) using cDNA microarrays and quantitative real time polymerase chain reaction (QPCR) analyses. For tadpoles reared through metamorphosis, we measured tadpole growth and development, as well as time to, mass at, and survival to metamorphosis. Although carbaryl did not significantly impact tadpole development, metamorphosis, or survival, clear exposure-related alterations in both tail and brain transcript levels were evident when tadpoles were exposed to carbaryl, particularly in tadpoles exposed at weeks 8 and 16 post-hatching, indicating both short-term and long-term alterations in mRNA expression. These results indicate that carbaryl can have long-lasting effects on brain development when exposure occurs at sensitive developmental stages, which may have implications for animal fitness and function later in the life cycle. PMID:23399446

  9. Insecticide susceptibility of Phlebotomus argentipes & assessment of vector control in two districts of West Bengal, India

    PubMed Central

    Kumar, Vijay; Shankar, Lokesh; Kesari, Shreekant; Bhunia, Gouri Shankar; Dinesh, Diwakar Singh; Mandal, Rakesh; Das, Pradeep

    2015-01-01

    Background & objectives: Kala-azar or visceral leishmanisis (VL) is known to be endemic in several States of India including West Bengal (WB). Only meager information is available on the vector dynamics of its vector species, Phlebotomus argentipes particularly in relation to control measure from this State. Hence, a pilot study was undertaken to assess the control strategy and its impact on vector in two endemic districts of WB, India. Methods: Two villages each from the two districts, Maldah and Burdwan, were selected for the study. Seasonal variation of sandflies was observed during pre-monsoon, post-monsoon and winter seasons. Susceptibility test of P. argentipes against DDT and bioassay on DDT sprayed wall and on long lasting insecticide nets (LN) Perma Net® 2.0 were conducted as per the WHO standard methods. Results: P. argentipes density was high during March to October. Susceptibility status of P. argentipes ranged from 40 to 61.54 per cent. Bioassay test showed 57.89 per cent mortality against LN PermaNet®-2.0. and 50 per cent against DDT on wall within 30 min of exposure. Interpretation & conclusions: Despite the integrated vector management approach, the sandfly population was high in the study area. The reason could be development of resistance in P. argentipes against DDT and low effectiveness of LN PermaNet®-2.0. The more pragmatic step will be to conduct large studies to monitor the susceptibility level in P. argentipes against DDT. PMID:26354219

  10. Targeting the Genital Tract Mucosa with a Lipopeptide/Recombinant Adenovirus Prime/Boost Vaccine Induces Potent and Long-Lasting CD8+ T Cell Immunity Against Herpes: Importance of Myeloid Differentiation Factor 881

    PubMed Central

    Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; BenMohamed, Lbachir

    2012-01-01

    Targeting the mucosal immune system of the genital tract (GT) with subunit vaccines failed to induce potent and durable local CD8+ T cell immunity, crucial for protection against many sexually transmitted viral (STV) pathogens, including herpes simplex virus type 2 (HSV-2) that causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8+ T cell immunity to protect the female genital tract from herpes. The lipopeptide and the rAdv5 vaccine express the immunodominant HSV-2 CD8+ T cell epitope (gB498-505) and both were delivered intravaginally (IVAG) in the progesterone-induced B6 mouse model of genital herpes. Compared to its homologous lipopeptide/lipopeptide (Lipo/Lipo); the Lipo/rAdv5 prime/boost immunized mice: (i) developed potent and sustained HSV-specific CD8+ T cells, detected in both the GT draining nodes (GT-DLN) and in the vaginal mucosa (VM); (ii) had significantly lower virus titers; (iii) had decreased overt signs of genital herpes disease; and (iv) did not succumb to lethal infection (p < 0.005), following intravaginal HSV-2 challenge. Polyfunctional CD8+ T cells, producing IFN-γ, TNF-α and IL-2 and exhibiting cytotoxic activity, were associated with protection (p < 0.005). The protective CD8+ T cell response was significantly compromised in the absence of the adaptor myeloid differentiation factor 88 (MyD88) (p = 0.0001). Taken together, these findings indicate that targeting the VM with a Lipo/rAdv5 prime/boost vaccine elicits a potent, MyD88-dependent, and long-lasting mucosal CD8+ T cell protective immunity against sexually transmitted herpes infection and disease. PMID:23018456

  11. Lipo-oxytocin-1, a Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups, Has Long-Lasting Effects on Anxiety-Related Behavior and Social Avoidance in CD157 Knockout Mice.

    PubMed

    Mizuno, Akira; Cherepanov, Stanislav M; Kikuchi, Yusuke; Fakhrul, Azam Akm; Akther, Shirin; Deguchi, Kisaburo; Yoshihara, Toru; Ishihara, Katsuhiko; Shuto, Satoshi; Higashida, Haruhiro

    2015-01-01

    Oxytocin (OT) is a nonapeptide hormone that is secreted into the brain and blood circulation. OT has not only classical neurohormonal roles in uterine contraction and milk ejection during the reproductive phase in females, but has also been shown to have new pivotal neuromodulatory roles in social recognition and interaction in both genders. A single administration of OT through nasal spray increases mutual recognition and trust in healthy subjects and psychiatric patients, suggesting that OT is a potential therapeutic drug for autism spectrum disorders, schizophrenia, and some other psychiatric disorders. Although the mechanism is not well understood, it is likely that OT can be transported into the brain where it activates OT receptors to exert its function in the brain. However, the amount transported into the brain may be low. To ensure equivalent effects, an OT analog with long-lasting and effective blood-brain barrier penetration properties would be beneficial for use as a therapeutic drug. Here, we designed and synthesized a new oxytocin analog, lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated at the amino group of the cysteine9 residue and the phenolic hydroxyl group of the tyrosine8 residue of the OT molecule. To determine whether LOT-1 actually has an effect on the central nervous system, we examined its effects in a CD157 knockout model mouse of the non-motor psychiatric symptoms of Parkinson's disease. Similar to OT, this analog rescued anxiety-like behavior and social avoidance in the open field test with the social target in a central arena 30 min after intraperitoneal injection in CD157 knockout mice. When examined 24 h after injection, the mice treated with LOT-1 displayed more recovery than those given OT. The results suggest that LOT-1 has a functional advantage in recovery of social behavioral impairment, such as those caused by neurodegenerative diseases, autism spectrum disorders, and schizophrenia. PMID:25612002

  12. Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

    PubMed

    Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2014-10-01

    Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. PMID:25196393

  13. Lipo-oxytocin-1, a Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups, Has Long-Lasting Effects on Anxiety-Related Behavior and Social Avoidance in CD157 Knockout Mice

    PubMed Central

    Mizuno, Akira; Cherepanov, Stanislav M.; Kikuchi, Yusuke; Fakhrul, Azam AKM; Akther, Shirin; Deguchi, Kisaburo; Yoshihara, Toru; Ishihara, Katsuhiko; Shuto, Satoshi; Higashida, Haruhiro

    2015-01-01

    Oxytocin (OT) is a nonapeptide hormone that is secreted into the brain and blood circulation. OT has not only classical neurohormonal roles in uterine contraction and milk ejection during the reproductive phase in females, but has also been shown to have new pivotal neuromodulatory roles in social recognition and interaction in both genders. A single administration of OT through nasal spray increases mutual recognition and trust in healthy subjects and psychiatric patients, suggesting that OT is a potential therapeutic drug for autism spectrum disorders, schizophrenia, and some other psychiatric disorders. Although the mechanism is not well understood, it is likely that OT can be transported into the brain where it activates OT receptors to exert its function in the brain. However, the amount transported into the brain may be low. To ensure equivalent effects, an OT analog with long-lasting and effective blood-brain barrier penetration properties would be beneficial for use as a therapeutic drug. Here, we designed and synthesized a new oxytocin analog, lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated at the amino group of the cysteine9 residue and the phenolic hydroxyl group of the tyrosine8 residue of the OT molecule. To determine whether LOT-1 actually has an effect on the central nervous system, we examined its effects in a CD157 knockout model mouse of the non-motor psychiatric symptoms of Parkinson’s disease. Similar to OT, this analog rescued anxiety-like behavior and social avoidance in the open field test with the social target in a central arena 30 min after intraperitoneal injection in CD157 knockout mice. When examined 24 h after injection, the mice treated with LOT-1 displayed more recovery than those given OT. The results suggest that LOT-1 has a functional advantage in recovery of social behavioral impairment, such as those caused by neurodegenerative diseases, autism spectrum disorders, and schizophrenia. PMID:25612002

  14. Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

    PubMed Central

    2014-01-01

    Porcine circovirus type 2 (PCV2) vaccination represents an important measure to cope with PCV2 infection; however, data regarding the modulation of the immune cell compartment are still limited, especially under field conditions. This study is aimed at investigating the features of the cellular immune response in conventional piglets induced by vaccination using a capsid (Cap) protein-based PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural infection. Immune reactivity was evaluated by quantifying peripheral cell subsets involved in the anti-viral response and characterizing the interferon-gamma (IFN-γ) secreting cell (SC) responsiveness both in vivo and upon in vitro whole PCV2 recall. The vaccination triggered an early and intense IFN-γ secreting cell response and induced the activation of peripheral lymphocytes. The early increase of IFN-γ SC frequencies resulted in a remarkable and transient tendency to increased IFN-γ productivity in vaccinated pigs. In vaccinated animals, soon before the onset of infection occurred 15-16 weeks post-vaccination, the recalled PCV2-specific immune response was characterized by moderate PCV2-specific IFN-γ secreting cell frequencies and augmented productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon infection, unvaccinated animals showed very high frequencies of IFN-γ secreting cells and a tendency to lower productivity, which paralleled with effector CD4–CD8+ cytotoxic cell responsiveness. The study shows that PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFN-γ secreting cells that potentially played a role in preventing the onset of infection; the extent and duration of this reactivity can be an important feature for evaluating the protective immunity induced by vaccination. PMID:24735253

  15. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

    SciTech Connect

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-12-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 {mu}g/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 {mu}g/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.

  16. Exendin-4-loaded PLGA microspheres relieve cerebral ischemia/reperfusion injury and neurologic deficits through long-lasting bioactivity-mediated phosphorylated Akt/eNOS signaling in rats.

    PubMed

    Chien, Chiang-Ting; Jou, Ming-Jia; Cheng, Tai-Yu; Yang, Chih-Hui; Yu, Tzu-Ying; Li, Ping-Chia

    2015-11-01

    Glucagon-like peptide-1 (GLP-1) receptor activation in the brain provides neuroprotection. Exendin-4 (Ex-4), a GLP-1 analog, has seen limited clinical usage because of its short half-life. We developed long-lasting Ex-4-loaded poly(D,L-lactide-co-glycolide) microspheres (PEx-4) and explored its neuroprotective potential against cerebral ischemia in diabetic rats. Compared with Ex-4, PEx-4 in the gradually degraded microspheres sustained higher Ex-4 levels in the plasma and cerebrospinal fluid for at least 2 weeks and improved diabetes-induced glycemia after a single subcutaneous administration (20 μg/day). Ten minutes of bilateral carotid artery occlusion (CAO) combined with hemorrhage-induced hypotension (around 30 mm Hg) significantly decreased cerebral blood flow and microcirculation in male Wistar rats subjected to streptozotocin-induced diabetes. CAO increased cortical O2(-) levels by chemiluminescence amplification and prefrontal cortex edema by T2-weighted magnetic resonance imaging analysis. CAO significantly increased aquaporin 4 and glial fibrillary acidic protein expression and led to cognition deficits. CAO downregulated phosphorylated Akt/endothelial nitric oxide synthase (p-Akt/p-eNOS) signaling and enhanced nuclear factor (NF)-κBp65/intercellular adhesion molecule-1 (ICAM-1) expression, endoplasmic reticulum (ER) stress, and apoptosis in the cerebral cortex. PEx-4 was more effective than Ex-4 to improve CAO-induced oxidative injury and cognitive deficits. The neuroprotection provided by PEx-4 was through p-Akt/p-eNOS pathways, which suppressed CAO-enhanced NF-κB/ICAM-1 signaling, ER stress, and apoptosis. PMID:26058696

  17. Insect sodium channels and insecticide resistance

    PubMed Central

    2011-01-01

    Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells. Although most of our knowledge about sodium channels is derived from decades of studies of mammalian isoforms, research on insect sodium channels is revealing both common and unique aspects of sodium channel biology. In particular, our understanding of the molecular dynamics and pharmacology of insect sodium channels has advanced greatly in recent years, thanks to successful functional expression of insect sodium channels in Xenopus oocytes and intensive efforts to elucidate the molecular basis of insect resistance to insecticides that target sodium channels. In this review, I discuss recent literature on insect sodium channels with emphases on the prominent role of alternative splicing and RNA editing in the generation of functionally diverse sodium channels in insects and the current understanding of the interactions between insect sodium channels and insecticides. PMID:17206406

  18. Insecticide residues on weathered passerine carcass feet

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Butterbrodt, J.J.; Mengelkoch, J.; MacDougall, K.; Williams, B.; Pendergrass, P.

    2003-01-01

    Nine brown-headed cowbirds (Molothrus ater) were exposed to turf srayed with either EarthCare? (25% diazinon; 477 L a.i./ha) or Ortho-Klor? (12 .6% chlorpyrifos; 5.21 L a.i./ha.). Birds were euthanized and one foot from each bird was weathered outdoors for up to 28 days and the other foot was kept frozen until residue analysis. When compared to the unweathered feet, feet weathered for 28 days retained 43% and 37% of the diazinon and chlorpyrifors, respectively. Insecticide residues were below the level of detection (1.0 ppm) on control feet. Weathered feet may be used for determining organophosphorus insecticide exposure to birds.

  19. Insecticide Control in a Dengue Epidemics Model

    NASA Astrophysics Data System (ADS)

    Rodrigues, Helena Sofia; Monteiro, M. Teresa T.; Torres, Delfim F. M.

    2010-09-01

    A model for the transmission of dengue disease is presented. It consists of eight mutually-exclusive compartments representing the human and vector dynamics. It also includes a control parameter (insecticide) in order to fight the mosquitoes. The main goal of this work is to investigate the best way to apply the control in order to effectively reduce the number of infected humans and mosquitoes. A case study, using data of the outbreak that occurred in 2009 in Cape Verde, is presented.

  20. Insecticide tolerance of Culex nigripalpus in Florida.

    PubMed

    Boike, A H; Rathburn, C B; Floore, T G; Rodriguez, H M; Coughlin, J S

    1989-12-01

    Larval susceptibility tests of Culex nigripalpus populations from various areas of Florida have shown resistance to several organophosphorus insecticides since 1984. Although the degree of resistance is low (2 to 7 times), it can be termed tolerance and appears to be the greatest for fenthion, followed by temephos, naled and malathion. It is suggested that pesticide runoff from lawns, golf courses and agricultural and urban areas may play a role in developing resistance in Florida mosquito populations. PMID:2614401

  1. Innovative applications for insect viruses: towards insecticide sensitization.

    PubMed

    Lapied, Bruno; Pennetier, Cédric; Apaire-Marchais, Véronique; Licznar, Patricia; Corbel, Vincent

    2009-04-01

    The effective management of emerging insect-borne disease is dependent on the use of safe and efficacious chemical insecticides. Given the inherent ability of insects to develop resistance, it is essential to propose innovative strategies because insecticides remain the most important element of integrated approaches to vector control. Recently, intracellular phosphorylation and dephosphorylation of membrane receptors and ion channels targeted by insecticides have been described as new processes for increasing the sensitivity of insecticides. An efficient method might be to infect host insects with recombinant viruses overexpressing specific protein phosphatases/kinases known to regulate specific insecticide-sensitive targets. This attractive strategy could lead to sensitization of the insects, thus reducing the doses of insecticides and increasing the efficacy of treatments. PMID:19251330

  2. Insecticide Resistance and Management Strategies in Urban Ecosystems

    PubMed Central

    Zhu, Fang; Lavine, Laura; O’Neal, Sally; Lavine, Mark; Foss, Carrie; Walsh, Douglas

    2016-01-01

    The increased urbanization of a growing global population makes imperative the development of sustainable integrated pest management (IPM) strategies for urban pest control. This emphasizes pests that are closely associated with the health and wellbeing of humans and domesticated animals. Concurrently there are regulatory requirements enforced to minimize inadvertent exposures to insecticides in the urban environment. Development of insecticide resistance management (IRM) strategies in urban ecosystems involves understanding the status and mechanisms of insecticide resistance and reducing insecticide selection pressure by combining multiple chemical and non-chemical approaches. In this review, we will focus on the commonly used insecticides and molecular and physiological mechanisms underlying insecticide resistance in six major urban insect pests: house fly, German cockroach, mosquitoes, red flour beetle, bed bugs and head louse. We will also discuss several strategies that may prove promising for future urban IPM programs. PMID:26751480

  3. TRP Channels in Insect Stretch Receptors as Insecticide Targets.

    PubMed

    Nesterov, Alexandre; Spalthoff, Christian; Kandasamy, Ramani; Katana, Radoslav; Rankl, Nancy B; Andrés, Marta; Jähde, Philipp; Dorsch, John A; Stam, Lynn F; Braun, Franz-Josef; Warren, Ben; Salgado, Vincent L; Göpfert, Martin C

    2015-05-01

    Defining the molecular targets of insecticides is crucial for assessing their selectivity and potential impact on environment and health. Two commercial insecticides are now shown to target a transient receptor potential (TRP) ion channel complex that is unique to insect stretch receptor cells. Pymetrozine and pyrifluquinazon disturbed Drosophila coordination and hearing by acting on chordotonal stretch receptor neurons. This action required the two TRPs Nanchung (Nan) and Inactive (Iav), which co-occur exclusively within these cells. Nan and Iav together sufficed to confer cellular insecticide responses in vivo and in vitro, and the two insecticides were identified as specific agonists of Nan-Iav complexes that, by promoting cellular calcium influx, silence the stretch receptor cells. This establishes TRPs as insecticide targets and defines specific agonists of insect TRPs. It also shows that TRPs can render insecticides cell-type selective and puts forward TRP targets to reduce side effects on non-target species. PMID:25950634

  4. Insecticide Resistance and Management Strategies in Urban Ecosystems.

    PubMed

    Zhu, Fang; Lavine, Laura; O'Neal, Sally; Lavine, Mark; Foss, Carrie; Walsh, Douglas

    2016-01-01

    The increased urbanization of a growing global population makes imperative the development of sustainable integrated pest management (IPM) strategies for urban pest control. This emphasizes pests that are closely associated with the health and wellbeing of humans and domesticated animals. Concurrently there are regulatory requirements enforced to minimize inadvertent exposures to insecticides in the urban environment. Development of insecticide resistance management (IRM) strategies in urban ecosystems involves understanding the status and mechanisms of insecticide resistance and reducing insecticide selection pressure by combining multiple chemical and non-chemical approaches. In this review, we will focus on the commonly used insecticides and molecular and physiological mechanisms underlying insecticide resistance in six major urban insect pests: house fly, German cockroach, mosquitoes, red flour beetle, bed bugs and head louse. We will also discuss several strategies that may prove promising for future urban IPM programs. PMID:26751480

  5. Mechanisms of action of escapin, a bactericidal agent in the ink secretion of the sea hare Aplysia californica: rapid and long-lasting DNA condensation and involvement of the OxyR-regulated oxidative stress pathway.

    PubMed

    Ko, Ko-Chun; Tai, Phang C; Derby, Charles D

    2012-04-01

    The marine snail Aplysia californica produces escapin, an L-amino acid oxidase, in its defensive ink. Escapin uses L-lysine to produce diverse products called escapin intermediate products of L-lysine (EIP-K), including α-amino-ε-caproic acid, Δ¹-piperidine-2-carboxylic acid, and Δ²-piperidine-2-carboxylic acid. EIP-K and H₂O₂ together, but neither alone, is a powerful bactericide. Here, we report bactericidal mechanisms of escapin products on Escherichia coli. We show that EIP-K and H₂O₂ together cause rapid and long-lasting DNA condensation: 2-min treatment causes significant DNA condensation and killing, and 10-min treatment causes maximal effect, lasting at least 70 h. We isolated two mutants resistant to EIP-K plus H₂O₂, both having a single missense mutation in the oxidation regulatory gene, oxyR. A complementation assay showed that the mutated gene, oxyR(A233V), renders resistance to EIP-K plus H₂O₂, and a gene dosage effect leads to reduction of resistance for strains carrying wild-type oxyR. Temperature stress with EIP-K does not produce the bactericidal effect, suggesting the effect is due to a specific response to oxidative stress. The null mutant for any single DNA-binding protein--Dps, H-NS, Hup, Him, or MukB--was not resistant to EIP-K plus H₂O₂, suggesting that no single DNA-binding protein is necessary to mediate this bactericidal effect, but allowing for the possibility that EIP-K plus H₂O₂ could function through a combination of DNA-binding proteins. The bactericidal effect of EIP-K plus H₂O₂ was eliminated by the ferrous ion chelator 1,10-phenanthroline, and it was reduced by the hydroxyl radical scavenger thiourea, suggesting hydroxyl radicals mediate the effects of EIP-K plus H₂O₂. PMID:22232273

  6. Long lasting interactions between tectonic loading, unroofing, post-rift thermal subsidence and sedimentary transfers along the western margin of the Gulf of Mexico: Some insights from integrated quantitative studies

    NASA Astrophysics Data System (ADS)

    Roure, François; Alzaga-Ruiz, Humberto; Callot, Jean-Paul; Ferket, Helga; Granjeon, Didier; Gonzalez-Mercado, Graciela Esmeralda; Guilhaumou, Nicole; Lopez, Michel; Mougin, Pascal; Ortuno-Arzate, Salvador; Séranne, Michel

    2009-09-01

    After Jurassic rifting, numerous carbonate platforms (i.e., the Orizaba, Cordoba and Golden Lane-Tuxpan platforms) developed during the Lower and Middle Cretaceous episode of thermal subsidence along the western passive margin of the Gulf of Mexico, with intervening basinal domains (i.e., the Tampico-Misantla, Zongolica, Veracruz and Deep Gulf of Mexico - DGM - basins). During the Late Cretaceous-Paleocene, the east-verging Sierra Madre Oriental thrust belt developed, resulting in tectonic uplift and unroofing of the allochthonous units (i.e. tectonic units made up of former Orizaba and Cordoba platforms and Zongolica Basin series). This new topography provided also an important source of clastics to feed the adjacent foredeep, where coeval tectonic loading accounted for the bending of the foreland lithosphere. However, shallow water facies or even emersion persisted until the Eocene in the forebulge area (at the present location of the Golden Lane), preventing locally the clastics to reach the DGM. This topographic barrier was ultimately bypassed by the clastics only during the Oligocene and Neogene, once (1) the prograding clastic wedge had exceeded accommodation, and (2) the long lasting thermal subsidence of the passive margin could overpass the effect of the bending and force the former bulge to sink. Numerous paleo-thermo-meters (Tmax, Ro), paleo-thermo-barometers (fluid inclusions), PVT and coupled forward kinematic and thermal modeling have been used to calibrate and date the progressive unroofing of the thrust belt. Coupled tectonic and sedimentologic modeling was applied in the foreland to predict the distribution of sand versus shale ratios in the Oligocene to Plio-Quaternary clastic sedimentary wedge of the passive margin, where gravitational gliding of post-Eocene series occurred during the Neogene along major listric faults. Mantle dynamics are advocated as the main process accounting for post-orogenic uplift and regional tilting of the basement

  7. A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    PubMed

    Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

    2016-02-01

    Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. PMID:26593980

  8. Insecticides suppress natural enemies and increase pest damage in cabbage.

    PubMed

    Bommarco, Riccardo; Miranda, Freddy; Bylund, Helena; Björkman, Christer

    2011-06-01

    Intensive use of pesticides is common and increasing despite a growing and historically well documented awareness of the costs and hazards. The benefits from pesticides of increased yields from sufficient pest control may be outweighed by developed resistance in pests and killing of beneficial natural enemies. Other negative effects are human health problems and lower prices because of consumers' desire to buy organic products. Few studies have examined these trade-offs in the field. Here, we demonstrate that Nicaraguan cabbage (Brassica spp.) farmers may suffer economically by using insecticides as they get more damage by the main pest diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), at the same time as they spend economic resources on insecticides. Replicated similarly sized cabbage fields cultivated in a standardized manner were either treated with insecticides according common practice or not treated with insecticides over two seasons. Fields treated with insecticides suffered, compared with nontreated fields, equal or, at least in some periods of the seasons, higher diamondback moth pest attacks. These fields also had increased leaf damage on the harvested cabbage heads. Weight and size of the heads were not affected. The farmers received the same price on the local market irrespective of insecticide use. Rates of parasitized diamondback moth were consistently lower in the treated fields. Negative effects of using insecticides against diamondback moth were found for the density of parasitoids and generalist predatory wasps, and tended to affect spiders negatively. The observed increased leaf damages in insecticide-treated fields may be a combined consequence of insecticide resistance in the pest, and of lower predation and parasitization rates from naturally occurring predators that are suppressed by the insecticide applications. The results indicate biological control as a viable and economic alternative pest management strategy

  9. Insect hormones and their derivatives as insecticides

    PubMed Central

    Bowers, William S.

    1971-01-01

    The hormonal control of moulting, reproduction, and diapause in insects has little or no relationship to any similar phenomena in other animals, and the hormones involved in these processes are unlike any known hormones of vertebrates. The availability of pure chemicals with high biological activity has permitted an astonishing increase in research on insect hormones. At present, understanding of insect endocrinology is far too incomplete to justify much speculation about the possibility of using insect hormones as insecticides. However, the preliminary studies discussed in this paper give reason for hope, and the results justify further effort. PMID:4938025

  10. INSECTICIDE CONCENTRATIONS IN AIR AFTER APPLICATION OF PEST CONTROL STRIPS

    EPA Science Inventory

    Contamination of air in homes due to spraying of pesticides is of concern to the public. A pest control strip which kills creeping and crawling insects by contact is one method of reducing the amount of insecticide in the air. Several different insecticides are now available in t...

  11. ANDROGEN RECEPTOR ANTAGONISM BY THE ORGANOPHOSPHATE INSECTICIDE FENITROTHION

    EPA Science Inventory

    Androgen receptor antagonism by the organophosphate insecticide fenitrothion. Tamura, H., Maness, S.C., Reischmann, K. Dorman, D.C., Gray, L.E., and Gaido, K.W. (2000). Toxicol. Sci.

    Organophosphate insecticides represent one of the most widely used classes of pesticide...

  12. Conifer flavonoid compounds inhibit detoxification enzymes and synergize insecticides.

    PubMed

    Wang, Zhiling; Zhao, Zhong; Cheng, Xiaofei; Liu, Suqi; Wei, Qin; Scott, Ian M

    2016-02-01

    Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase inhibitors from phytochemicals could provide potential new insecticide synergists. Conifer tree species contain flavonoids, such as taxifolin, that inhibit in vitro GST activity. The objectives were to test the relative effectiveness of taxifolin as an enzyme inhibitor and as an insecticide synergist in combination with the organophosphorous insecticide, Guthion (50% azinphos-methyl), and the botanical insecticide, pyrethrum, using an insecticide-resistant Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say) strain. Both taxifolin and its isomer, quercetin, increased the mortality of 1(st) instar CPB larvae after 48h when combined with Guthion, but not pyrethrum. Taxifolin had greater in vitro esterase inhibition compared with the commonly used esterase inhibitor, S, S, S-tributyl phosphorotrithioate (DEF). An in vivo esterase and GST inhibition effect after ingestion of taxifolin was measured, however DEF caused a greater suppression of esterase activity. This study demonstrated that flavonoid compounds have both in vitro and in vivo esterase inhibition, which is likely responsible for the insecticide synergism observed in insecticide-resistant CPB. PMID:26821651

  13. Evaluating Coverage and Efficacy of Insecticides to Control Navel Orangeworm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel method employing eggs was designed to assess insecticide coverage in pistachio clusters. Strips of paper towel with known numbers of eggs were pinned into pistachio clusters immediately before insecticide application. The eggs were removed 24-48 hours after application and placed on diet, re...

  14. Effectiveness of vegetated agricultural drainage ditches in mitigating insecticide loadings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have shown that runoff and spray-drift are important sources of nonpoint-source insecticide pollution of surface waters. Owing to this, public concern over the presence of insecticides in surface and ground water has resulted in intensive scientific efforts to find economical, yet environmen...

  15. Effects of organophosphorus insecticides on sage grouse in southeastern Idaho

    USGS Publications Warehouse

    Blus, L.J.; Staley, C.S.; Henny, C.J.; Pendleton, G.W.; Craig, T.H.; Craig, E.H.; Halford, D.K.

    1989-01-01

    Unverified reports indicated die-offs of sage grouse have occurred since the 1970s in southeastern Idaho. Some verification that organophosphorus insecticides were involved was obtained in 1981 and 1983. A radio telemetry study indicated that dimethoate was responsible for most mortality. Methamidophos also acounted for mortality. Sage grouse populations may be adversely affected by organophosphorus insecticides.

  16. LABORATORY EVALUATION OF TARNISHED PLANT BUG TOLERANCE TO INSECTICIDES, 2002.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Formulated insecticides were evaluated in the laboratory for toxicity to tarnished plant bugs. Spray chamber bioassay were conducted by applying insecticides to cotton terminals. Treatment consisted of Vydate applied at 0.33 lb (AI)/acre and Intruder at 0.042, 0.056, 0.084 and 0.0112 lb (AI)/acre....

  17. Distribution and Efficacy of Aerosol Insecticides in Commercial Facilities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aerosol insecticides are being viewed as a potential alternative to fumigations in commercial milling, processing, and storage facilities. Although there are a number of insecticides and delivery systems available for use, there are little published data regarding efficacy and performance in actual ...

  18. Interactions of transgenic Bacillus thuringiensis insecticidal crops with spiders (Araneae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetically modified crops expressing insecticidal proteins from Bacillus thuringiensis (Bt) have dramatically increased in acreage since their introduction in the mid-1990’s. Although the insecticidal mechanisms of Bt target specific pests, concerns persist regarding direct and indirect effects on...

  19. MITIGATION OF PYRETHROID INSECTICIDES IN A MISSISSIPPI DELTA CONSTRUCTED WETLAND

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrethroid insecticides are commonly used in intensively cultivated agricultural areas for crop pest control. During storm runoff events, these insecticides may be transported into aquatic receiving systems where they have the potential to damage fish and invertebrates. Constructed wetlands are on...

  20. Ecotoxicological study of insecticide effects on arthropods in common bean.

    PubMed

    de Barros, Emerson Cristi; Ventura, Hudson Vaner; Gontijo, Pablo Costa; Pereira, Renata Ramos; Picanço, Marcelo Coutinho

    2015-01-01

    Arthropods are an important group of macroorganisms that work to maintain ecosystem health. Despite the agricultural benefits of chemical control against arthropod pests, insecticides can cause environmental damage. We examined the effects of one and two applications of the insecticides chlorfenapyr (0.18 liters a.i. ha-1) and methamidophos (0.45 liters a.i. ha-1), both independently and in combination, on arthropods in plots of common bean. The experiment was repeated for two growing seasons. Principal response curve, richness estimator, and Shannon-Wiener diversity index analyses were performed. The insecticides generally affected the frequency, richness, diversity, and relative abundance of the arthropods. In addition, the arthropods did not experience recovery after the insecticide applications. The results suggest that the insecticide impacts were sufficiently drastic to eliminate many taxa from the studied common bean plots. PMID:25700537

  1. Production of Insecticide Degradates in Juices: Implications for Risk Assessment.

    PubMed

    Radford, Samantha A; Panuwet, Parinya; Hunter, Ronald E; Barr, Dana Boyd; Ryan, P Barry

    2016-06-01

    This study was designed to observe the production of degradates of two organophosphorus insecticides and one pyrethroid insecticide in beverages. Purified water, white grape juice, apple juice, and red grape juice were fortified with 500 ng/g malathion, chlorpyrifos, and permethrin, and aliquots were extracted for malathion dicarboxylic acid (MDA), 3,5,6-trichloro-2-pyridinol (TCPy), and 3-phenoxybenzoic acid (3-PBA) several times over a 15 day period of being stored in the dark at 2.5 °C. Overall, first-order kinetics were observed for production of MDA, and statistically significant production of TCPy was also observed. Statistically significant production of 3-phenoxybenzoic acid was not observed. Results indicate that insecticides degrade in food and beverages, and this degradation may lead to preexisting insecticide metabolites in the beverages. Therefore, it is suggested that caution should be exercised when using urinary insecticide metabolites to assess exposure and risk. PMID:27213611

  2. Ecotoxicological Study of Insecticide Effects on Arthropods in Common Bean

    PubMed Central

    de Barros, Emerson Cristi; Ventura, Hudson Vaner; Gontijo, Pablo Costa; Pereira, Renata Ramos; Picanço, Marcelo Coutinho

    2015-01-01

    Arthropods are an important group of macroorganisms that work to maintain ecosystem health. Despite the agricultural benefits of chemical control against arthropod pests, insecticides can cause environmental damage. We examined the effects of one and two applications of the insecticides chlorfenapyr (0.18 liters a.i. ha-1) and methamidophos (0.45 liters a.i. ha-1), both independently and in combination, on arthropods in plots of common bean. The experiment was repeated for two growing seasons. Principal response curve, richness estimator, and Shannon–Wiener diversity index analyses were performed. The insecticides generally affected the frequency, richness, diversity, and relative abundance of the arthropods. In addition, the arthropods did not experience recovery after the insecticide applications. The results suggest that the insecticide impacts were sufficiently drastic to eliminate many taxa from the studied common bean plots. PMID:25700537

  3. An Operational Framework for Insecticide Resistance Management Planning

    PubMed Central

    Chanda, Emmanuel; Thomsen, Edward K.; Musapa, Mulenga; Kamuliwo, Mulakwa; Brogdon, William G.; Norris, Douglas E.; Masaninga, Freddie; Wirtz, Robert; Sikaala, Chadwick H.; Muleba, Mbanga; Craig, Allen; Govere, John M.; Ranson, Hilary; Hemingway, Janet; Seyoum, Aklilu; Macdonald, Michael B.

    2016-01-01

    Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future. PMID:27089119

  4. Insecticidal sesquiterpene from Alpinia oxyphylla against Drosophila melanogaster.

    PubMed

    Miyazawa, M; Nakamura, Y; Ishikawa, Y

    2000-08-01

    In the course of screening for novel naturally occurring insecticides from Chinese crude drugs, an MeOH extract of Alpinia oxyphylla was found to possess insecticidal activity against larvae of Drosophila melanogaster Meigen. From the extract, an insecticidal compound was isolated by bioassay-guided fractionation and identified as nootkatone (1) by GC, GC-MS, and (1)H and (13)C NMR spectroscopy. In bioassays for insecticidal activity, 1 showed an LC(50) value of 11.5 micromol/mL of diet against larvae of D. melanogaster and an LD(50) value of 96 microg/adult against adults. Epinootkatol (1A), however, showed slight insecticidal activity in both assays, indicating that the carbonyl group at the 2-position in 1 was the important function for enhanced activity of 1. PMID:10956162

  5. An Operational Framework for Insecticide Resistance Management Planning.

    PubMed

    Chanda, Emmanuel; Thomsen, Edward K; Musapa, Mulenga; Kamuliwo, Mulakwa; Brogdon, William G; Norris, Douglas E; Masaninga, Freddie; Wirtz, Robert; Sikaala, Chadwick H; Muleba, Mbanga; Craig, Allen; Govere, John M; Ranson, Hilary; Hemingway, Janet; Seyoum, Aklilu; Macdonald, Michael B; Coleman, Michael

    2016-05-01

    Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future. PMID:27089119

  6. Botanical insecticides inspired by plant-herbivore chemical interactions.

    PubMed

    Miresmailli, Saber; Isman, Murray B

    2014-01-01

    Plants have evolved a plethora of secondary chemicals to protect themselves against herbivores and pathogens, some of which have been used historically for pest management. The extraction methods used by industry render many phytochemicals ineffective as insecticides despite their bioactivity in the natural context. In this review, we examine how plants use their secondary chemicals in nature and compare this with how they are used as insecticides to understand why the efficacy of botanical insecticides can be so variable. If the commercial production of botanical insecticides is to become a viable pest management option, factors such as production cost, resource availability, and extraction and formulation techniques need be considered alongside innovative application technologies to ensure consistent efficacy of botanical insecticides. PMID:24216132

  7. Averting a malaria disaster: will insecticide resistance derail malaria control?

    PubMed

    Hemingway, Janet; Ranson, Hilary; Magill, Alan; Kolaczinski, Jan; Fornadel, Christen; Gimnig, John; Coetzee, Maureen; Simard, Frederic; Roch, Dabiré K; Hinzoumbe, Clément Kerah; Pickett, John; Schellenberg, David; Gething, Peter; Hoppé, Mark; Hamon, Nicholas

    2016-04-23

    World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe. PMID:26880124

  8. Can nutrients mask community responses to insecticide mixtures?

    PubMed

    Alexander, Alexa C; Luis, Ana T; Culp, Joseph M; Baird, Donald J; Cessna, Allan J

    2013-09-01

    The ecological effect of simultaneous exposure to two nutrient gradients, three insecticides and different predator intensities was investigated over a 3-week period in 80 outdoor, artificial streams using field-collected benthic invertebrates. The experimental design consisted of a 2 × 5 factorial structure with two nutrient levels (oligotrophic or mesotrophic) and five concentrations of the ternary insecticide mixture consisting of the insecticides (chlorpyrifos, dimethoate and imidacloprid). Equivalent toxic unit doses were summed to create a ternary insecticide dose (e.g., 0.1 + 0.1 + 0.1 = 0.3 TU) resulting in a range of ternary insecticide mixture toxicity (i.e., control groundwater, 0.3, 0.6, 0.9 and 1.2 TU). Two genera of insect predators, Gomphus spp. (Odonata) and Agnetina spp. (Plecoptera) were also added into each replicate stream, at densities and sizes comparable to those found at our collection site, to evaluate how the contribution of predators may change in nutrient limited (oligotrophic) versus amended (mesotrophic) systems. We describe a causal mechanism whereby the combined action of nutrients and insecticides reshaped aquatic community structure by interacting through multiple pathways. Specifically, mesotrophic conditions reduced the toxic effects of ternary insecticide mixtures for aquatic insects which, in some cases, appeared to increase abundance of aquatic insects. However, higher levels of insecticides in mesotrophic streams negated this effect and were even more toxic; for example, to aquatic insect grazers than the same insecticide doses in oligotrophic treatment levels. Effects of predators were only significant in oligotrophic streams. Evidence is provided as to how nutrient and contaminant interactions can greatly complicate the assessment of community level responses to insecticide mixtures due to direct and indirect effects of the resulting changes in the density of different genera and functional feeding groups within a

  9. Risks of neonicotinoid insecticides to honeybees

    PubMed Central

    Fairbrother, Anne; Purdy, John; Anderson, Troy; Fell, Richard

    2014-01-01

    The European honeybee, Apis mellifera, is an important pollinator of agricultural crops. Since 2006, when unexpectedly high colony losses were first reported, articles have proliferated in the popular press suggesting a range of possible causes and raising alarm over the general decline of bees. Suggested causes include pesticides, genetically modified crops, habitat fragmentation, and introduced diseases and parasites. Scientists have concluded that multiple factors in various combinations—including mites, fungi, viruses, and pesticides, as well as other factors such as reduction in forage, poor nutrition, and queen failure—are the most probable cause of elevated colony loss rates. Investigators and regulators continue to focus on the possible role that insecticides, particularly the neonicotinoids, may play in honeybee health. Neonicotinoid insecticides are insect neurotoxicants with desirable features such as broad-spectrum activity, low application rates, low mammalian toxicity, upward systemic movement in plants, and versatile application methods. Their distribution throughout the plant, including pollen, nectar, and guttation fluids, poses particular concern for exposure to pollinators. The authors describe how neonicotinoids interact with the nervous system of honeybees and affect individual honeybees in laboratory situations. Because honeybees are social insects, colony effects in semifield and field studies are discussed. The authors conclude with a review of current and proposed guidance in the United States and Europe for assessing the risks of pesticides to honeybees. PMID:24692231

  10. Synthetic pyrethroid insecticides: a dermatological evaluation.

    PubMed Central

    Flannigan, S A; Tucker, S B; Key, M M; Ross, C E; Fairchild, E J; Grimes, B A; Harrist, R B

    1985-01-01

    Synthetic pyrethroids are lipophilic insecticides whose biological activity seems to be directly related to their chemical structure. In this investigation differences in cutaneous sensation were detected by human participants between synthetic pyrethroids with a cyano group in the (S)-configuration of the 3-phenoxybenzyl alcohol of their molecular structure (fenvalerate) and those that do not (permethrin). A strong relation was noted between insecticidal potency and degree of induced cutaneous sensation for the alpha-cyano and non-cyano pyrethroids, with a prominent difference between the two. No sensation was observed by any of the same participants on topical exposure to the inert ingredients of these agents. A linear correlation between concentration and degree of induced dysaethesia was observed for both pyrethroids. Regressing the cutaneous sensation on the common logarithm of concentration resulted in a regression equation of Y = 84.0 + 31.0X1 for fenvalerate and Y = 27.5 + 15.8X1 for permethrin. A highly efficacious therapeutic agent for pyrethroid exposure was noted to be dl-alpha tocopherol acetate. An impressive degree of inhibition of paraesthesia resulted from the topical application of vitamin E acetate, with a therapeutic index of almost 100%. PMID:4005189

  11. Risks of neonicotinoid insecticides to honeybees.

    PubMed

    Fairbrother, Anne; Purdy, John; Anderson, Troy; Fell, Richard

    2014-04-01

    The European honeybee, Apis mellifera, is an important pollinator of agricultural crops. Since 2006, when unexpectedly high colony losses were first reported, articles have proliferated in the popular press suggesting a range of possible causes and raising alarm over the general decline of bees. Suggested causes include pesticides, genetically modified crops, habitat fragmentation, and introduced diseases and parasites. Scientists have concluded that multiple factors in various combinations-including mites, fungi, viruses, and pesticides, as well as other factors such as reduction in forage, poor nutrition, and queen failure-are the most probable cause of elevated colony loss rates. Investigators and regulators continue to focus on the possible role that insecticides, particularly the neonicotinoids, may play in honeybee health. Neonicotinoid insecticides are insect neurotoxicants with desirable features such as broad-spectrum activity, low application rates, low mammalian toxicity, upward systemic movement in plants, and versatile application methods. Their distribution throughout the plant, including pollen, nectar, and guttation fluids, poses particular concern for exposure to pollinators. The authors describe how neonicotinoids interact with the nervous system of honeybees and affect individual honeybees in laboratory situations. Because honeybees are social insects, colony effects in semifield and field studies are discussed. The authors conclude with a review of current and proposed guidance in the United States and Europe for assessing the risks of pesticides to honeybees. PMID:24692231

  12. Impact of Insecticide Resistance on the Effectiveness of Pyrethroid-Based Malaria Vectors Control Tools in Benin: Decreased Toxicity and Repellent Effect.

    PubMed

    Agossa, Fiacre R; Gnanguenon, Virgile; Anagonou, Rodrigue; Azondekon, Roseric; Aïzoun, Nazaire; Sovi, Arthur; Oké-Agbo, Frédéric; Sèzonlin, Michel; Akogbéto, Martin C

    2015-01-01

    Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS) in semi-field conditions and long lasting insecticidal nets (LLINs) in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46%) but high for other predominant species such as Mansonia africana (93% to 97%). There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001). Furthermore, mortality was 23.71% for OlyseNet® and 39.06% for PermaNet®. However, with laboratory susceptible "Kisumu", mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted. PMID:26674643

  13. Impact of Insecticide Resistance on the Effectiveness of Pyrethroid-Based Malaria Vectors Control Tools in Benin: Decreased Toxicity and Repellent Effect

    PubMed Central

    Agossa, Fiacre R.; Gnanguenon, Virgile; Anagonou, Rodrigue; Azondekon, Roseric; Aïzoun, Nazaire; Sovi, Arthur; Oké-Agbo, Frédéric; Sèzonlin, Michel; Akogbéto, Martin C.

    2015-01-01

    Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS) in semi-field conditions and long lasting insecticidal nets (LLINs) in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46%) but high for other predominant species such as Mansonia africana (93% to 97%). There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001). Furthermore, mortality was 23.71% for OlyseNet® and 39.06% for PermaNet®. However, with laboratory susceptible “Kisumu”, mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted. PMID:26674643

  14. Infrared video tracking of Anopheles gambiae at insecticide-treated bed nets reveals rapid decisive impact after brief localised net contact

    PubMed Central

    Parker, Josephine E.A.; Angarita-Jaimes, Natalia; Abe, Mayumi; Towers, Catherine E.; Towers, David; McCall, Philip J.

    2015-01-01

    Long-lasting insecticidal bed nets (LLINs) protect humans from malaria transmission and are fundamental to malaria control worldwide, but little is known of how mosquitoes interact with nets. Elucidating LLIN mode of action is essential to maintain or improve efficacy, an urgent need as emerging insecticide resistance threatens their future. Tracking multiple free-flying Anopheles gambiae responding to human-occupied bed nets in a novel large-scale system, we characterised key behaviours and events. Four behavioural modes with different levels of net contact were defined: swooping, visiting, bouncing and resting. Approximately 75% of all activity occurred at the bed net roof where multiple brief contacts were focussed above the occupant’s torso. Total flight and net contact times were lower at LLINs than untreated nets but the essential character of the response was unaltered. LLINs did not repel mosquitoes but impacted rapidly: LLIN contact of less than 1 minute per mosquito during the first ten minutes reduced subsequent activity; after thirty minutes, activity at LLINs was negligible. Velocity measurements showed that mosquitoes detected nets, including unbaited untreated nets, prior to contact. This is the most complete characterisation of mosquito-LLIN interactions to date, and reveals many aspects of LLIN mode of action, important for developing the next generation of LLINs. PMID:26323965

  15. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    PubMed

    Ibrahim, Sulaiman S; Riveron, Jacob M; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J I; Wondji, Charles S

    2015-10-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  16. Scepticism towards insecticide treated mosquito nets for malaria control in rural community in north-western Tanzania.

    PubMed

    Nnko, Soori E; Whyte, Susan R; Geissler, Wenzel P; Aagaard-Hansen, Jens

    2012-04-01

    Despite existence of effective tools for malaria control, malaria continues to be one of the leading killer diseases especially among under-five year children and pregnant women in poor rural populations of Sub Saharan Africa. In Tanzania Mainland the disease contributes to 39.4% of the total OPD attendances. In terms of mortality, malaria is known to be responsible for more than one third of deaths among children of age below 5 years and also contributes for up to one fifth of deaths among pregnant women. This paper is based on a study conducted in a rural community along the shores of Lake Victoria in Mwanza region, North-Western Tanzania. The study explores reasons for scepticism and low uptake of insecticide treated mosquito nets (ITNs) that were promoted through social marketing strategy for malaria control prior to the introduction of long lasting nets (LLN). The paper breaks from traditional approach that tend to study low uptake of health interventions in terms of structural practical constraints--cost, accessibility, everyday priorities--or in terms of cognition--insufficient knowledge of benefits e.g. ignorance of public health messages. This paper has shown that, the majority of people who could afford the prices of ITNs and who knew where to obtain the insecticides did not necessarily buy them. This suggests that, although people tend to report cost-related factors as a barrier against the use of ITNs, there are other critical concerns at work. Without underestimating the practical factors, our study have recommended to consider critical examinations of those other concerns that hinder optimal utilization of ITN for malaria control, and the basis for those concerns. PMID:26591730

  17. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector

    PubMed Central

    Ibrahim, Sulaiman S.; Riveron, Jacob M.; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J. I.; Wondji, Charles S.

    2015-01-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  18. Evaluation of the Effectiveness of Insecticide Treated Materials for Household Level Dengue Vector Control

    PubMed Central

    Vanlerberghe, Veerle; Villegas, Elci; Oviedo, Milagros; Baly, Alberto; Lenhart, Audrey; McCall, P. J.; Van der Stuyft, Patrick

    2011-01-01

    Objective To assess the operational effectiveness of long-lasting insecticide treated materials (ITMs), when used at household level, for the control of Aedes aegypti in moderately infested urban and suburban areas. Methods In an intervention study, ITMs consisting of curtains and water jar-covers (made from PermaNet) were distributed under routine field conditions in 10 clusters (5 urban and 5 suburban), with over 4000 houses, in Trujillo, Venezuela. Impact of the interventions were determined by comparing pre-and post-intervention measures of the Breteau index (BI, number of positive containers/100 houses) and pupae per person index (PPI), and by comparison with indices from untreated areas of the same municipalities. The effect of ITM coverage was modeled. Results At distribution, the proportion of households with ≥1 ITM curtain was 79.7% in urban and 75.2% in suburban clusters, but decreased to 32.3% and 39.0%, respectively, after 18 months. The corresponding figures for the proportion of jars using ITM covers were 34.0% and 50.8% at distribution and 17.0% and 21.0% after 18 months, respectively. Prior to intervention, the BI was 8.5 in urban clusters and 42.4 in suburban clusters, and the PPI was 0.2 and 0.9, respectively. In both urban and suburban clusters, the BI showed a sustained 55% decrease, while no discernable pattern was observed at the municipal level. After controlling for confounding factors, the percentage ITM curtain coverage, but not ITM jar-cover coverage, was significantly associated with both entomological indices (Incidence Rate Ratio = 0.98; 95%CI 0.97–0.99). The IRR implied that ITM curtain coverage of at least 50% was necessary to reduce A. aegypti infestation levels by 50%. Conclusion Deployment of insecticide treated window curtains in households can result in significant reductions in A. aegypti levels when dengue vector infestations are moderate, but the magnitude of the effect depends on the coverage attained, which itself

  19. Susceptibility of Cimex lectularius (Hemiptera: Cimicidae) to pyrethroid insecticides and to insecticidal dusts with or without pyrethroid insecticides.

    PubMed

    Anderson, John F; Cowles, Richard S

    2012-10-01

    Relative increases of bed bug, Cimex lectularius L., populations are probably due in large measure to their resistance to pyrethroids, which have been used extensively against urban pests. A Connecticut population of bed bugs was assessed for sensitivity to pyrethroids and exposed to commonly-used commercial insecticides applied to various substrates on which the residues were allowed to age for 0-24 wk. Type I and type II pyrethroids differed in toxicity when applied at a high dosage (1 microg) per bed bug. Some type II pyrethroids (cyfluthrin, lambda-cyhalothrin, cis-cypermethrin, and deltamethrin) caused > 80% mortality, whereas exposure to type I pyrethroids caused < 5% mortality over 72 h (with one exception, pyrethrins caused 23% mortality). Dust products were not affected by residue aging; mortality response over time of exposure closely fit (R2 > 0.95) an exponential rise to a maximum model from which the survival half-life (S1/2) was calculated directly. Tempo Dust (Bayer Environmental Science, Montvale, NJ) killed bed bugs relatively quickly, as did Syloid 244 (Grace Davison, Columbia, MD) and Drione (Bayer Environmental Science, Montvale, NJ) on hardboard and mattress fabric substrates (S1/2 < 1 d); DeltaDust (Bayer Environmental Science, Montvale, NJ) provided a relatively slow kill (S1/2 approximately equal to 3.5 d). The sprayable pyrethroids, Cyonara 9.7 (Insecticide Control solutions, Pasadena, TX) and D-Force HPX Aerosol 0.06% (Waterbury Companies, Waterbury, CT), displayed reduced residual toxicity as they aged; the mortality was < 50% on some substrates after 4 d. Desiccant dusts, with their physical mode of action and long residual activity, appear to be superior to sprayable pyrethroid products for killing bed bugs. PMID:23156178

  20. Insecticide resistance in head lice: clinical, parasitological and genetic aspects.

    PubMed

    Durand, R; Bouvresse, S; Berdjane, Z; Izri, A; Chosidow, O; Clark, J M

    2012-04-01

    Insecticide treatment resistance is considered to be a major factor in the increasing number of infestations by head lice. The large insecticide selection pressure induced by conventional topical pediculicides has led to the emergence and spread of resistance in many parts of the world. Possible mechanisms of resistance include accelerated detoxification of insecticides by enzyme-mediated reduction, esterification, oxidation that may be overcome by synergistic agents such as piperonyl butoxide, alteration of the binding site, e.g. altered acetylcholinesterase or altered nerve voltage-gated sodium channel, and knockdown resistance (kdr). Clinical, parasitological and molecular data on resistance to conventional topical pediculicides show that treatments with neurotoxic insecticides have suffered considerable loss of activity worldwide. In particular, resistance to synthetic pyrethroids has become prominent, probably because of their extensive use. As other treatment options, including non-insecticidal pediculicides such as dimeticone, are now available, the use of older insecticides, such as lindane and carbaryl, should be minimized, owing to their loss of efficacy and safety concerns. The organophosphorus insecticide malathion remains effective, except in the UK, mostly in formulations that include terpineol. PMID:22429458

  1. Virus and calcium: an unexpected tandem to optimize insecticide efficacy.

    PubMed

    Apaire-Marchais, Véronique; Ogliastro, Mylène; Chandre, Fabrice; Pennetier, Cédric; Raymond, Valérie; Lapied, Bruno

    2016-04-01

    The effective control of insect pests is based on the rational use of the most efficient and safe insecticide treatments. To increase the effects of classical insecticides and to avoid the ability of certain pest insects to develop resistance, it is essential to propose novel strategies. Previous studies have shown that calcium-dependent phosphorylation/dephosphorylation is now considered as a new cellular mechanism for increasing the target sensitivity to insecticides. Because it is known that virus entry is correlated with intracellular calcium concentration rise, this report attempts to present the most important data relevant to the feasibility of combining an insect virus such as baculovirus or densovirus with an insecticide. In this case, the insect virus is not used as a bioinsecticide but acts as a synergistic agent able to trigger calcium rise and to activate calcium-dependent intracellular signalling pathways involved in the increase of the membrane receptors and/or ion channels sensitivity to insecticides. This virus-insecticide mixture represents a promising alternative to optimize the efficacy of insecticides against insect pests while reducing the doses. PMID:26743399

  2. Simulating cholinesterase inhibition in birds caused by dietary insecticide exposure

    USGS Publications Warehouse

    Corson, M.S.; Mora, M.A.; Grant, W.E.

    1998-01-01

    We describe a stochastic simulation model that simulates avian foraging in an agricultural landscape to evaluate factors affecting dietary insecticide exposure and to predict post-exposure cholinesterase (ChE) inhibition. To evaluate the model, we simulated published field studies and found that model predictions of insecticide decay and ChE inhibition reasonably approximated most observed results. Sensitivity analysis suggested that foraging location usually influenced ChE inhibition more than diet preferences or daily intake rate. Although organophosphorus insecticides usually caused greater inhibition than carbamate insecticides, insecticide toxicity appeared only moderately important. When we simulated impact of heavy insecticide applications during breeding seasons of 15 wild bird species, mean maximum ChE inhibition in most species exceeded 20% at some point. At this level of inhibition, birds may experience nausea and/or may exhibit minor behavioral changes. Simulated risk peaked in April-May and August-September and was lowest in July. ChE inhibition increased with proportion of vegetation in the diet. This model, and ones like it, may help predict insecticide exposure of and sublethal ChE inhibition in grassland animals, thereby reducing dependence of ecological risk assessments on field studies alone.

  3. Induced tolerance from a sublethal insecticide leads to cross-tolerance to other insecticides.

    PubMed

    Hua, Jessica; Jones, Devin K; Relyea, Rick A

    2014-04-01

    As global pesticide use increases, the ability to rapidly respond to pesticides by increasing tolerance has important implications for the persistence of nontarget organisms. A recent study of larval amphibians discovered that increased tolerance can be induced by an early exposure to low concentrations of a pesticide. Since natural systems are often exposed to a variety of pesticides that vary in mode of action, we need to know whether the induction of increased tolerance to one pesticide confers increased tolerance to other pesticides. Using larval wood frogs (Lithobates sylvaticus), we investigated whether induction of increased tolerance to the insecticide carbaryl (AChE-inhibitor) can induce increased tolerance to other insecticides that have the same mode of action (chlorpyrifos, malathion) or a different mode of action (Na(+)channel-interfering insecticides; permethrin, cypermethrin). We found that embryonic exposure to sublethal concentrations of carbaryl induced higher tolerance to carbaryl and increased cross-tolerance to malathion and cypermethrin but not to chlorpyrifos or permethrin. In one case, the embryonic exposure to carbaryl induced tolerance in a nonlinear pattern (hormesis). These results demonstrate that that the newly discovered phenomenon of induced tolerance also provides induced cross-tolerance that is not restricted to pesticides with the same mode of action. PMID:24579768

  4. [Insecticide resistance in lice collected from homeless people in Moscow].

    PubMed

    Lopatina, Iu V; Eremina, O Iu

    2011-01-01

    Permethrin and malathion resistance in body and head lice collected from homeless people in Moscow was investigated in March 2009 to March 2010. Most micropopulations were found to have permethrin-resistant individuals. Their proportion varied from 8.7 to 100%. Cross resistance of body lice to 5 insecticides (the pyrethroids permethrin, d-phenothrin, cypermethrin, deltamethrin, and the organic chlorine compound DDT) was revealed in one case. The lice remained susceptible to organic phosphorus insecticides (fenthion, malathion). The data on permethrin resistance in the lice, obtained by the standard method (immersion of the insects into an insecticide solution), correlated with those yielded by the modified WHO method. PMID:22308710

  5. Synthesis and insecticidal activity of heptafluoroisopropyl-containing benzoylphenylurea structures.

    PubMed

    Zhang, Jian; Tang, Xiuhong; Ishaaya, Isaac; Cao, Song; Wu, Jingjing; Yu, Jinlong; Li, Hui; Qian, Xuhong

    2010-03-10

    Fourteen novel heptafluoroisopropyl-containing benzoylphenylureas were designed and synthesized. Their insecticidal activities against armyworm ( Pseudaletia separata Walker) were examined and compared with the commercial product diflubenzuron. Three compounds (IIi, IIj, and IIk) showed excellent insecticidal effect, and their activity resembled that of diflubenzuron. Compound IIi also showed nearly the same insecticidal activity as novaluron on African cotton leafworm ( Spodoptera littoralis ). Furthermore, results from a field trial indicated that 5% EC IIi exhibited similar efficacy in comparison with chlorfluazuron and hexaflumuron against imported cabbage worm ( Pieris rapae L.) and diamondback moth ( Plutella xylostella ), respectively. PMID:20014763

  6. Resistance to insecticides in Heliothine Lepidoptera: a global view

    PubMed Central

    McCaffery, A. R.

    1998-01-01

    The status of resistance to organophosphate, carbamate, cyclodiene and pyrethroid insecticides in the heliothine Lepidoptera is reviewed. In particular, resistance in the tobacco budworm, Heliothis virescens, and the corn earworm, Helicoverpa zea, from the New World, and the cotton bollworm, Helicoverpa armigera, from the Old World, are considered in detail. Particular emphasis has been placed on resistance to the most widely used of these insecticide groups, the pyrethroids. In each case, the incidence and current status of resistance are considered before a detailed view of the mechanisms of resistance is given. Controversial issues regarding the nature of mechanisms of resistance to pyrethroid insecticides are discussed. The implications for resistance management are considered.

  7. A novel insecticidal serotype of Clostridium bifermentans.

    PubMed

    Seleena, P; Lee, H L; Lecadet, M M

    1997-12-01

    A novel Clostridium bifermentans strain toxic to mosquito larvae on ingestion was isolated from a soil sample collected from secondary forest floor. This strain was designated as serovar paraiba (C. b. paraiba) according to its specific H antigen. Clostridium bifermentans paraiba is most toxic to Anopheles maculatus Theobald larvae (LC50 = 0.038 mg/liter), whereas toxicity to Aedes aegypti (Linn.) (LC50 = 0.74 mg/liter) and Culex quinquefasciatus Say (LC50 = 0.11 mg/liter) larvae was 20 and 3 times lower, respectively. The toxicity to An. maculatus larvae is as high as that of Bacillus thuringiensis serovar israelensis. C. b. paraiba was also found to exhibit significant per os insecticidal activity toward adult Musca domestica (Linn.). PMID:9474569

  8. Insecticidal and repellent activities of pyrethroids to the three major pyrethroid-resistant malaria vectors in western Kenya

    PubMed Central

    2014-01-01

    Background The dramatic success of insecticide treated nets (ITNs) and long-lasting insecticidal nets (LLINs) in African countries has been countered by the rapid development of pyrethroid resistance in vector mosquitoes over the past decade. One advantage of the use of pyrethroids in ITNs is their excito-repellency. Use of the excito-repellency of pyrethroids might be biorational, since such repellency will not induce or delay the development of any physiological resistance. However, little is known about the relationship between the mode of insecticide resistance and excito-repellency in pyrethroid-resistant mosquitoes. Methods Differences in the reactions of 3 major malaria vectors in western Kenya to pyrethroids were compared in laboratory tests. Adult susceptibility tests were performed using World Health Organization (WHO) test tube kits for F1 progenies of field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s., and laboratory colonies of An. gambiae s.s. and An. arabiensis. The contact repellency to pyrethroids or permethrin-impregnated LLINs (Olyset® Nets) was evaluated with a simple choice test modified by WHO test tubes and with the test modified by the WHO cone bioassay test. Results Field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s. showed high resistance to both permethrin and deltamethrin. The allelic frequency of the point mutation in the voltage-gated sodium channel (L1014S) in An. gambiae s.s. was 99.3–100%, while no point mutations were detected in the other 2 species. The frequency of takeoffs from the pyrethroid-treated surface and the flying times without contacting the surface increased significantly in pyrethroid-susceptible An. gambiae s.s. and An. arabiensis colonies and wild An. arabiensis and An. funestus s.s. colonies, while there was no significant increase in the frequency of takeoffs or flying time in the An. gambiae s.s. wild colony. Conclusion A different repellent reaction was observed in

  9. Neonicotinoid insecticides: highlights of a symposium on strategic molecular designs.

    PubMed

    Tomizawa, Motohiro; Casida, John E

    2011-04-13

    Neonicotinoids are the newest of the five major classes of insecticides (the others are chlorinated hydrocarbons, organophosphorus compounds, methylcarbamates, and pyrethroids), and they make up approximately one-fourth of the world insecticide market. Nithiazine was the lead compound from Shell Development Co. in California later optimized by Shinzo Kagabu of Nihon Tokushu Noyaku Seizo to increase the potency and photostability, resulting in imidacloprid and thiacloprid. These discoveries are the basis for the International Award for Research in Agrochemicals of the American Chemical Society presented in 2010 to Professor Shinzo Kagabu. Five other neonicotinoids were added by others for the current set of seven commercial compounds. This symposium considers the progress in discovery and development of novel chemotype nicotinic insecticides with enhanced effectiveness, unique biological properties, and maximal safety. Chemorational approaches considered include physicochemical properties, metabolic activation and detoxification, and chemical and structural biology aspects potentially facilitating receptor structure-guided insecticide design. PMID:21077684

  10. Design, synthesis and insecticidal activity of novel phenylurea derivatives.

    PubMed

    Sun, Jialong; Zhou, Yuanming

    2015-01-01

    A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and 1H-NMR spectral data. All of the compounds were evaluated for the insecticidal activity against the third instars larvae of Spodoptera exigua Hiibner, Plutella xyllostella Linnaeus, Helicoverpa armigera Hubner and Pieris rapae Linne respectively, at the concentration of 10 mg/L. The results showed that all of the derivatives displayed strong insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, chlorbenzuron and metaflumizone. Among the synthesized compounds, 3b, 3d, 3f, 4b and 4g displayed broad spectrum insecticidal activity. PMID:25808149

  11. USING ARRAY TECHNOLOGY TO IDENTIFY POTENTIAL BIOMARKERS FOR PYRETHROID INSECTICIDES.

    EPA Science Inventory

    Pyrethroid insecticides affect nervous system function by disruption of sodium channels in nerve membranes. FQPA requirements for assessing cumulative risk have increased the need for rapid and sensitive biomarkers of effect. This project aims to develop biochemical markers of n...

  12. Toxicity and bioaccumulation of the insecticide "Raid" in Wister rats.

    PubMed

    Achudume, Albert C; Nwoha, Polycarp C; Ibe, Joseph N

    2009-08-01

    Toxicity and bioaccumulation of the insecticide "Raid" was determined to assess total animal dietary exposures in a nonoccupational environment. The study focused primarily on dietary exposure concentrations (25-960 microg/g) of the ingredients of Raid administered to rats for 10 days. Tissue concentrations of the insecticide were determined by a high-pressure liquid chromatography method, whereas established methods were used to assess the tissue levels of glucose-6-phosphate and lactic acid dehydrogenase. Results show that animal mortality progressively increased with increasing concentrations while growth (in weight) decreased. Bioaccumulation of the insecticide in the tissues was in the order of lipid > muscle > liver > brain. The indices of toxicity showed no significant effect in brain, but significant reduction of glucose-6-phosphatase and lactic acid dehydrogenase levels were observed in muscle and liver. These results suggest an inhibition of some key metabolic enzymes resulting from accumulation of the insecticide components in the tissues. PMID:18785263

  13. Mechanism of Insect Resistance to the Microbial Insecticide Bacillus thuringiensis

    NASA Astrophysics Data System (ADS)

    van Rie, J.; McGaughey, W. H.; Johnson, D. E.; Barnett, B. D.; van Mellaert, H.

    1990-01-01

    Receptor binding studies show that resistance of a laboratory-selected Plodia interpunctella strain to a Bacillus thuringiensis insecticidal crystal protein (ICP) is correlated with a 50-fold reduction in affinity of the membrane receptor for this protein. The strain is sensitive to a second type of ICP that apparently recognizes a different receptor. Understanding the mechanism of resistance will provide strategies to prevent or delay resistance and hence prolong the usefulness of B. thuringiensis ICPs as environmentally safe insecticides.

  14. Impact of some selected insecticides application on soil microbial respiration.

    PubMed

    Latif, M A; Razzaque, M A; Rahman, M M

    2008-08-15

    The aim of present study was to investigate the impact of selected insecticides used for controlling brinjal shoot and fruit borer on soil microorganisms and to find out the insecticides or nontoxic to soil microorganism the impact of nine selected insecticides on soil microbial respiration was studied in the laboratory. After injection of different insecticides solutions, the soil was incubated in the laboratory at room temperature for 32 days. The amount of CO2 evolved due to soil microbial respiration was determined at 2, 4, 8, 16, 24 and 32 days of incubation. Flubendiamide, nimbicidine, lambda-cyhalothrin, abamectin and thiodicarb had stimulatory effect on microbial respiration during the initial period of incubation. Chlorpyriphos, cartap and carbosulfan had inhibitory effect on microbial respiration and cypermethrin had no remarkable effect during the early stage of incubation. The negative effect of chlorpyriphos, cartap and carbosulfan was temporary, which was disappeared after 4 days of insecticides application. No effect of the selected insecticides on soil microorganisms was observed after 24 or 32 days of incubation. PMID:19266909

  15. Design, synthesis and insecticidal evaluation of aryloxy dihalopropene derivatives.

    PubMed

    Yang, Ji-Chun; Li, Miao; Wu, Qiao; Liu, Chang-Ling; Chang, Xiu-Hui

    2016-02-01

    Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical structures were confirmed by (1)H NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity against P. xylostella at 6.25mg/L, while pyridalyl showed 50% insecticidal activity at the same concentration. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control of P. xylostella at 75-150g a.i./ha, and the mortality of P. xylostella for treatment with compound 10e at 75g a.i./ha was equivalent to pyridalyl at 105g a.i./ha. PMID:26432606

  16. Sublethal and transgenerational effects of insecticides in developing Trichogramma galloi (Hymenoptera: Trichogrammatidae) : toxicity of insecticides to Trichogramma galloi.

    PubMed

    Costa, Mariana Abreu; Moscardini, Valéria Fonseca; da Costa Gontijo, Pablo; Carvalho, Geraldo Andrade; de Oliveira, Rodrigo Lopes; de Oliveira, Harley Nonato

    2014-10-01

    This study assessed the transgenerational effects of insecticides in developing Trichogramma galloi (Hymenoptera: Trichogrammatidae). Laboratory bioassays were performed in which five insecticides were sprayed on egg-larval, pre-pupal and pupal stages of the parasitoid. The interaction between insecticides and development stages of the parasitoid was not significant for the rate of F0 emergence. All insecticides significantly reduced the emergence of wasps, with the lowest emergence observed when they were applied to the pupal stage. For the sex ratio, only spinosad applied to the pre-pupal stage and triflumuron applied on the egg-larval and pre-pupal stages did not differ from the controls. Triflumuron applied to pre-pupae did not lead to any difference in the parasitism rate of the treated generation (F0) when compared to the control. There were no significant differences among survival curves for females of F0 when all insecticides were sprayed on the egg-larval stage. Both concentrations of lambda-cyhalothrin + thiamethoxam reduced female pre-pupal survival, and all treatments reduced female pupal survival. In addition, we observed a transgenerational effect of the insecticides on emergence and sex ratio of next generation (F1). Lambda-cyhalothrin + thiamethoxam (Min) applied to the pre-pupae and pupae, the maximum rate of the same insecticides applied to the egg-larvae and pre-pupae, and spinosad applied to pre-pupae all significantly reduced the adults emergence of T. galloi F1 generation. Only triflumuron did not alter the F1 sex ratio. These bioassays provide a basis for better understanding the effects of insecticide use on beneficial parasitoids. PMID:25011923

  17. Male Mosquitoes as Vehicles for Insecticide

    PubMed Central

    Mains, James W.; Brelsfoard, Corey L.; Dobson, Stephen L.

    2015-01-01

    Background The auto-dissemination approach has been shown effective at treating cryptic refugia that remain unaffected by existing mosquito control methods. This approach relies on adult mosquito behavior to spread larvicide to breeding sites at levels that are lethal to immature mosquitoes. Prior studies demonstrate that ‘dissemination stations,’ deployed in mosquito-infested areas, can contaminate adult mosquitoes, which subsequently deliver the larvicide to breeding sites. In some situations, however, preventative measures are needed, e.g., to mitigate seasonal population increases. Here we examine a novel approach that combines elements of autocidal and auto-dissemination strategies by releasing artificially reared, male mosquitoes that are contaminated with an insecticide. Methodology Laboratory and field experiments examine for model-predicted impacts of pyriproxyfen (PPF) directly applied to adult male Aedes albopictus, including (1) the ability of PPF-treated males to cross-contaminate females and to (2) deliver PPF to breeding sites. Principal Findings Similar survivorship was observed in comparisons of PPF-treated and untreated males. Males contaminated both female adults and oviposition containers in field cage tests, at levels that eliminated immature survivorship. Field trials demonstrate an ability of PPF-treated males to transmit lethal doses to introduced oviposition containers, both in the presence and absence of indigenous females. A decline in the Ae. albopictus population was observed following the introduction of PPF-treated males, which was not observed in two untreated field sites. Conclusions/Significance The results demonstrate that, in cage and open field trials, adult male Ae. albopictus can tolerate PPF and contaminate, either directly or indirectly, adult females and immature breeding sites. The results support additional development of the proposed approach, in which male mosquitoes act as vehicles for insecticide delivery

  18. Insecticide mixtures could enhance the toxicity of insecticides in a resistant dairy population of Musca domestica L [corrected].

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Shad, Sarfraz Ali; Lee, Jong-Jin

    2013-01-01

    House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, emamectin benzoate and fipronil were assessed separately, and in mixtures against house flies. A field-collected population was significantly resistant to all the insecticides under investigation when compared with a laboratory susceptible strain. Most of the insecticide mixtures like one pyrethroid with other compounds evaluated under two conditions (1∶1-"A" and LC50: LC50-"B") significantly increased the toxicity of pyrethroids in the field population. Under both conditions, the combination indices of pyrethroids with other compounds, in most of the cases, were significantly below 1, suggesting synergism. The enzyme inhibitors, PBO and DEF, when used in combination with insecticides against the resistant population, toxicities of bifenthrin, cypermethrin, deltamethrin and emamectin were significantly increased, suggesting esterase and monooxygenase based resistance mechanism. The toxicities of bifenthrin, cypermethrin and deltamethrin in the resistant population of house flies could be enhanced by the combination with chlorpyrifos, profenofos, emamectin and fipronil. The findings of the present study might have practical significance for resistance management in house flies. PMID:23613758

  19. Cell Culture for Production of Insecticidal Viruses.

    PubMed

    Reid, Steven; Chan, Leslie C L; Matindoost, Leila; Pushparajan, Charlotte; Visnovsky, Gabriel

    2016-01-01

    While large-scale culture of insect cells will need to be conducted using bioreactors up to 10,000 l scale, many of the main challenges for cell culture-based production of insecticidal viruses can be studied using small-scale (20-500 ml) shaker/spinner flasks, either in free suspension or using microcarrier-based systems. These challenges still relate to the development of appropriate cell lines, stability of virus strains in culture, enhancing virus yields per cell, and the development of serum-free media and feeds for the desired production systems. Hence this chapter presents mainly the methods required to work with and analyze effectively insect cell systems using small-scale cultures. Outlined are procedures for quantifying cells and virus and for establishing frozen cells and virus stocks. The approach for maintaining cell cultures and the multiplicity of infection (MOI) and time of infection (TOI) parameters that should be considered for conducting infections are discussed.The methods described relate, in particular, to the suspension culture of Helicoverpa zea and Spodoptera frugiperda cell lines to produce the baculoviruses Helicoverpa armigera nucleopolyhedrovirus, HearNPV, and Anticarsia gemmatalis multicapsid nucleopolyhedrovirus, AgMNPV, respectively, and the production of the nonoccluded Oryctes nudivirus, OrNV, using an adherent coleopteran cell line. PMID:27565495

  20. [Insecticide resistance of Bemisia tabaci field populations].

    PubMed

    He, Yu-Xian; Weng, Qi-Yong; Huang, Jian; Liang, Zhi-Sheng; Lin, Gui-Jun; Wu, Dong-Dong

    2007-07-01

    Resistance to 13 insecticides in field populations of Bemisia tabaci from six regions (Fuzhou, Zhangzhou, Longyan, Sanming, Nanping, Ningde) of Fujian Province, China was monitored by adult leaf-dipping bioassay. Compared with the susceptible SUD-S strain, all the six field populations exhibited high levels of resistance to lambda-cyhalothrin (838.38-2460.52 fold), fenpropathrin (244.64-834.29 fold), cypermethrin (116.02-266.35 fold), deltamethrin (81.75-124.18 fold), acephate (425.18-875.56 fold) and chlorpyrifos (54.53-78.43 fold), moderate levels of resistance to dimethoate (14.16-17.66 fold), low to moderate levels of resistance to dichlorvos (6.23-11.25 fold) and low levels of resistance to methomyl (4.07-5.66 fold), respectively. Among these six field-collected populations, only Zhangzhou population had moderate resistance to imidacloprid, acetamiprid and thiamethoxam (23.08 fold, 10.32 fold and 24.60 fold, respectively). All field strains tested displayed no resistance to abamectin. PMID:17886654

  1. Federal chemist reports on insecticide dangers

    USGS Publications Warehouse

    DeWitt, J.B.

    1957-01-01

    There's been much discussion, and considerable argument, in recent years regarding the effects of crop dusting on game populations. In an attempt to get some of the answers, the U. S. Fish and Wildlife Service has been conducting a series of experiments, using captive quail? and pheasants.....By. feeding. specified amounts??of various insecticides, they found how 'much it would take to kill outright all test birds, how much to produce partIal kill, and how much would have relatively little effect. An interesting result? of the experiments was the proof that even non-fatal doses would stunt growth and reduce egg fertility, and that birds were unable to reproduce at all after two generations of exposure to these poisons....Of the cheriricals tested, aldrin and endrin were the most poisonous to the birds. If aldrin were applied at the rate of one pound per acre, each square? foot of ground would have enough poison? to kill two adult quail or 20 two-week-old birds.

  2. Pyrethroid insecticide residues on vegetable crops.

    PubMed

    Ripley, B D; Ritcey, G M; Harris, C R; Denommé, M A; Brown, P D

    2001-08-01

    Pyrethroid insecticides were applied on various vegetable crops as foliar treatments to determine dissipation rates. On Chinese broccoli (Guy Lon), Chinese mustard (Pak Choi) and Chinese cabbage (Kasumi, napa), fenvalerate was persistent with residues of 0.10, 0.14 and 0.11 mg kg-1, respectively, by day 21. Cypermethrin residues on head lettuce were below 0.1 mg kg-1 by day 10 but on the leafier romaine and endive varieties it was more persistent and required 14-19 days to dissipate below this concentration. After three applications, residues of cypermethrin in harvested carrots and of permethrin in eggplant were not detected on the day of application. On asparagus, deltamethrin and cypermethrin residues declined to less than 0.1 mg kg-1 by days 1 and 2, respectively; permethrin was more persistent, requiring more than 2 days to decline to less than 0.1 mg kg-1. Deltamethrin on dry (cooking) and Spanish onions was not detected on the day of application. On tomatoes, the concentration of permethrin was 0.093 mg kg-1 on the day of application and declined to about 0.05 mg kg-1 after 2-4 days. In general, permethrin, cypermethrin and deltamethrin residues declined to acceptable concentrations within an acceptable pre-harvest interval. Fenvalerate may be too persistent on these speciality crops unless a maximum residue limit > 0.1 mg kg-1 is permitted. PMID:11517721

  3. Mutagenic and cytotoxic activities of benfuracarb insecticide.

    PubMed

    Eren, Yasin; Erdoğmuş, Sevim Feyza; Akyıl, Dilek; Özkara, Arzu

    2016-08-01

    Benfuracarb is a carbamate insecticide used to control insect pests in vegetables and it has anti-acetylcholinesterase activity lower than other carbamates. Cytotoxic effects of benfuracarb were evaluated by using root growth inhibition (EC50), mitotic index (MI), and mitotic phase determinations on the root meristem cells of Allium cepa and mutagenic effects were determined in Salmonella typhymurium Ames test by TA98 and TA100 strains with and without metabolic activation. In Allium test, 1 % DMSO was used as negative control group and 10 ppm MMS was used as positive control group. 75 ppm concentration of benfuracarb was found as EC50. In MI and mitotic phases determination study, 37.5, 75 and 150 ppm doses of benfuracarb were used. Dose-dependent cytotoxic activity was found by root growth inhibition and MI studies. It was identified that mitotic inhibition activity of benfuracarb was higher than 10 ppm MMS. In Ames test, mutagenic activity was not observed and over 200 µg/plate of benfuracarb was determined as cytotoxic to S. typhymurium strains. Benfuracarb can be called as "mitotic inhibitor" but not called as mutagen. PMID:25381170

  4. Azobenzene Modified Imidacloprid Derivatives as Photoswitchable Insecticides: Steering Molecular Activity in a Controllable Manner

    NASA Astrophysics Data System (ADS)

    Xu, Zhiping; Shi, Lina; Jiang, Danping; Cheng, Jiagao; Shao, Xusheng; Li, Zhong

    2015-10-01

    Incorporating the photoisomerizable azobenzene into imidacloprid produced a photoswitchable insecticidal molecule as the first neonicotinoid example of remote control insecticide performance with spatiotemporal resolution. The designed photoswitchable insecticides showed distinguishable activity against Musca both in vivo and in vitro upon irradiation. Molecular docking study further suggested the binding difference of the two photoisomers. The generation of these photomediated insecticides provides novel insight into the insecticidal activity facilitating further investigation on the functions of insect nicotinic acetylcholine receptors and opens a novel way to control and study insect behavior on insecticide poisoning using light.

  5. Azobenzene Modified Imidacloprid Derivatives as Photoswitchable Insecticides: Steering Molecular Activity in a Controllable Manner

    PubMed Central

    Xu, Zhiping; Shi, Lina; Jiang, Danping; Cheng, Jiagao; Shao, Xusheng; Li, Zhong

    2015-01-01

    Incorporating the photoisomerizable azobenzene into imidacloprid produced a photoswitchable insecticidal molecule as the first neonicotinoid example of remote control insecticide performance with spatiotemporal resolution. The designed photoswitchable insecticides showed distinguishable activity against Musca both in vivo and in vitro upon irradiation. Molecular docking study further suggested the binding difference of the two photoisomers. The generation of these photomediated insecticides provides novel insight into the insecticidal activity facilitating further investigation on the functions of insect nicotinic acetylcholine receptors and opens a novel way to control and study insect behavior on insecticide poisoning using light. PMID:26434681

  6. Climate change, agricultural insecticide exposure, and risk for freshwater communities.

    PubMed

    Kattwinkel, Mira; Kühne, Jan-Valentin; Foit, Kaarina; Liess, Matthias

    2011-09-01

    Climate change exerts direct effects on ecosystems but has additional indirect effects due to changes in agricultural practice. These include the increased use of pesticides, changes in the areas that are cultivated, and changes in the crops cultivated. It is well known that pesticides, and in particular insecticides, affect aquatic ecosystems adversely. To implement effective mitigation measures it is necessary to identify areas that are affected currently and those that will be affected in the future. As a consequence, we predicted potential exposure to insecticide (insecticide runoff potential, RP) under current conditions (1990) and under a model scenario of future climate and land use (2090) using a spatially explicit model on a continental scale, with a focus on Europe. Space-for-time substitution was used to predict future levels of insecticide application, intensity of agricultural land use, and cultivated crops. To assess the indirect effects of climate change, evaluation of the risk of insecticide exposure was based on a trait-based, climate-insensitive indicator system (SPEAR, SPEcies At Risk). To this end, RP and landscape characteristics that are relevant for the recovery of affected populations were combined to estimate the ecological risk (ER) of insecticides for freshwater communities. We predicted a strong increase in the application of, and aquatic exposure to, insecticides under the future scenario, especially in central and northern Europe. This, in turn, will result in a severe increase in ER in these regions. Hence, the proportion of stream sites adjacent to arable land that do not meet the requirements for good ecological status as defined by the EU Water Framework Directive will increase (from 33% to 39% for the EU-25 countries), in particular in the Scandinavian and Baltic countries (from 6% to 19%). Such spatially explicit mapping of risk enables the planning of adaptation and mitigation strategies including vegetated buffer strips and

  7. Insecticide cytotoxicology in China: Current status and challenges.

    PubMed

    Zhong, Guohua; Cui, Gaofeng; Yi, Xin; Sun, Ranran; Zhang, Jingjing

    2016-09-01

    The insecticide cytotoxicology, as a new branch of toxicology, has rapidly developed in China. During the past twenty years, thousands of investigations have sprung up to evaluate the damages and clarify the mechanisms of insecticidal chemical substances to insect cells in vivo or in vitro. The mechanisms of necrosis, apoptosis or autophagy induced by synthetic or biogenic pesticides and virus infections have been systematically illuminated in many important models, including S2, BmN, SL-1, Sf21 and Sf9 cell lines. In addition, a variety of methods have also been applied to examine the effects of insecticides and elaborate the modes of action. As a result, many vital factors and pathways, such as cytochrome c, the Bcl-2 family and caspases, in mitochondrial signaling pathways, intracellular free calcium and lysosome signal pathways have been illuminated and drawn much attention. Benefiting from the application of insecticide cytotoxicology, natural products purifications, biological activities assessments of synthetic compounds and high throughput screening models have been accelerated in China. However, many questions remained, and there exist great challenges, especially in theory system, evaluation criterion, evaluation model, relationship between activity in vitro and effectiveness in vivo, and the toxicological mechanism. Fortunately, the generation of "omics" could bring opportunities for the development of insecticide cytotoxicology. PMID:27521907

  8. The global status of insect resistance to neonicotinoid insecticides.

    PubMed

    Bass, Chris; Denholm, Ian; Williamson, Martin S; Nauen, Ralf

    2015-06-01

    The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management. PMID:26047114

  9. Agricultural landscape simplification does not consistently drive insecticide use.

    PubMed

    Larsen, Ashley E

    2013-09-17

    The increase in agricultural production over the past 40 y has greatly altered land-use patterns, often resulting in simplified landscapes composed of large swaths of monocultures separated by small fragments of natural lands. These simplified landscapes may be more susceptible to insect pest pressure because of the loss of natural enemies and the increased size and connectivity of crop resources, and a recent analysis from a single year (2007) suggests this increased susceptibility results in increased insecticide use. I broaden the temporal analysis of this connection between landscape simplification and insecticide use by examining cross-sectional and panel data models from multiple decades (US Department of Agriculture Census of Agriculture years 2007, 2002, 1997, 1992, 1987) for seven Midwestern states composed of over 560 counties. I find that although the proportion of county in cropland--my metric for landscape simplification--was positively correlated with insecticide use in 2007, this relationship is absent or reversed in prior census years and when all years are analyzed together. This broader temporal perspective suggests that landscape simplification has inconsistent effects on insecticide use and that multiyear studies will be key to unlocking the true drivers of variation in insecticide application. PMID:24003135

  10. Mass Spectrometric Analyses of Organophosphate Insecticide Oxon Protein Adducts

    PubMed Central

    Thompson, Charles M.; Prins, John M.; George, Kathleen M.

    2010-01-01

    Objective Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. Data sources and extraction We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. Data synthesis A number of OP-based insecticides share common structural elements that result in predictable OP–protein adducts. The resultant OP–protein adducts show an increase in molecular mass that can be identified by MS and correlated with the OP agent. Customized OP-containing probes have also been used to tag and identify protein targets that can be identified by MS. Conclusions MS is a useful and emerging tool for the identification of proteins that are modified by activated organophosphate insecticides. MS can characterize the structure of the OP adduct and also the specific amino acid residue that forms the key bond with the OP. Each protein that is modified in a unique way by an OP represents a unique molecular biomarker that with further research can lead to new correlations with exposure. PMID:20056576

  11. Insecticide resistance in the bed bug comes with a cost.

    PubMed

    Gordon, Jennifer R; Potter, Michael F; Haynes, Kenneth F

    2015-01-01

    Adaptation to new environmental stress is often associated with an alteration of one or more life history parameters. Insecticide resistant populations of insects often have reduced fitness relative to susceptible populations in insecticide free environments. Our previous work showed that three populations of bed bugs, Cimex lectularius L., evolved significantly increased levels of resistance to one product containing both β-cyfluthrin and imidacloprid insecticides with only one generation of selection, which gave us an opportunity to explore potential tradeoffs between life history parameters and resistance using susceptible and resistant strains of the same populations. Life history tables were compiled by collecting weekly data on mortality and fecundity of bugs from each strain and treatment throughout their lives. Selection led to a male-biased sex ratio, shortened oviposition period, and decreased life-time reproductive rate. Generation time was shortened by selection, a change that represents a benefit rather than a cost. Using these life history characteristics we calculated that there would be a 90% return to pre-selection levels of susceptibility within 2- 6.5 generations depending on strain. The significant fitness costs associated with resistance suggest that insecticide rotation or utilization of non-insecticidal control tactics could be part of an effective resistance management strategy. PMID:26039510

  12. Insecticide susceptibility in mosquitoes (Diptera: Culicidae) from French Polynesia.

    PubMed

    Failloux, A B; Ung, A; Raymond, M; Pasteur, N

    1994-09-01

    Susceptibility to six organophosphate (OP), two pyrethroid (PY), and one carbamate (C) insecticides was investigated in Culex pipiens quinquefasciatus Say, Aedes aegypti (L.), and Aedes polynesiensis Marks larvae from the island of Tahiti. Cx. p. quinquefasciatus and Ae. aegypti were compared with susceptible reference strains treated simultaneously. A low, but significant, resistance to bromophos (4.6x), chlorpyrifos (5.7x), fenthion (2.4x), fenitrothion (5.0x), temephos (4.3x) and permethrin (2.1x) was found in Cx. p. quinquefasciatus, and to malathion (1.5x), temephos (2.3x), permethrin (1.8x) and propoxur (1.7x) in Ae. aegypti. Cx. p. quinquefasciatus was shown to possess over-produced esterases A2 and B2, which are known to be involved in resistance to OPs in other countries. Ae. polynesiensis was less resistant than the Ae. aegypti reference strain to all insecticides except temephos (1.8x) and permethrin (6.7x). To determine whether Ae. polynesiensis had developed resistance to these insecticides in Tahiti, a geographical survey covering 12 islands of the Society, Tuamotu, Tubuai, Marquesas, and Gambier archipelagoes was undertaken with three insecticides (temephos, deltamethrin, and permethrin). Two- to threefold variations in LC50S were observed among collections. Results are discussed in relationship to the level of insecticide exposure on the different islands. PMID:7966164

  13. Fungal infection counters insecticide resistance in African malaria mosquitoes

    PubMed Central

    Farenhorst, Marit; Mouatcho, Joel C.; Kikankie, Christophe K.; Brooke, Basil D.; Hunt, Richard H.; Thomas, Matthew B.; Koekemoer, Lizette L.; Knols, Bart G. J.; Coetzee, Maureen

    2009-01-01

    The evolution of insecticide resistance in mosquitoes is threatening the effectiveness and sustainability of malaria control programs in various parts of the world. Through their unique mode of action, entomopathogenic fungi provide promising alternatives to chemical control. However, potential interactions between fungal infection and insecticide resistance, such as cross-resistance, have not been investigated. We show that insecticide-resistant Anopheles mosquitoes remain susceptible to infection with the fungus Beauveria bassiana. Four different mosquito strains with high resistance levels against pyrethroids, organochlorines, or carbamates were equally susceptible to B. bassiana infection as their baseline counterparts, showing significantly reduced mosquito survival. Moreover, fungal infection reduced the expression of resistance to the key public health insecticides permethrin and dichlorodiphenyltrichloroethane. Mosquitoes preinfected with B. bassiana or Metarhizium anisopliae showed a significant increase in mortality after insecticide exposure compared with uninfected control mosquitoes. Our results show a high potential utility of fungal biopesticides for complementing existing vector control measures and provide products for use in resistance management strategies. PMID:19805146

  14. IRAC: Mode of action classification and insecticide resistance management.

    PubMed

    Sparks, Thomas C; Nauen, Ralf

    2015-06-01

    Insecticide resistance is a long standing and expanding problem for pest arthropod control. Effective insecticide resistance management (IRM) is essential if the utility of current and future insecticides is to be preserved. Established in 1984, the Insecticide Resistance Action Committee (IRAC) is an international association of crop protection companies. IRAC serves as the Specialist Technical Group within CropLife International focused on ensuring the long term efficacy of insect, mite and tick control products through effective resistance management for sustainable agriculture and improved public health. A key function of IRAC is the continued development of the Mode of Action (MoA) classification scheme, which provides up-to-date information on the modes of action of new and established insecticides and acaricides and which serves as the basis for developing appropriate IRM strategies for crop protection and vector control. The IRAC MoA classification scheme covers more than 25 different modes of action and at least 55 different chemical classes. Diversity is the spice of resistance management by chemical means and thus it provides an approach to IRM providing a straightforward means to identify potential rotation/alternation options. PMID:26047120

  15. Insecticide resistance in the bed bug comes with a cost

    PubMed Central

    Gordon, Jennifer R.; Potter, Michael F.; Haynes, Kenneth F.

    2015-01-01

    Adaptation to new environmental stress is often associated with an alteration of one or more life history parameters. Insecticide resistant populations of insects often have reduced fitness relative to susceptible populations in insecticide free environments. Our previous work showed that three populations of bed bugs, Cimex lectularius L., evolved significantly increased levels of resistance to one product containing both β-cyfluthrin and imidacloprid insecticides with only one generation of selection, which gave us an opportunity to explore potential tradeoffs between life history parameters and resistance using susceptible and resistant strains of the same populations. Life history tables were compiled by collecting weekly data on mortality and fecundity of bugs from each strain and treatment throughout their lives. Selection led to a male-biased sex ratio, shortened oviposition period, and decreased life-time reproductive rate. Generation time was shortened by selection, a change that represents a benefit rather than a cost. Using these life history characteristics we calculated that there would be a 90% return to pre-selection levels of susceptibility within 2- 6.5 generations depending on strain. The significant fitness costs associated with resistance suggest that insecticide rotation or utilization of non-insecticidal control tactics could be part of an effective resistance management strategy. PMID:26039510

  16. Broken promise? Taxes and tariffs on insecticide treated mosquito nets.

    PubMed

    Alilio, Martin; Mwenesi, Halima; Barat, Lawrence M; Payes, Roshelle M; Prysor-Jones, Suzanne; Diara, Malick; McGuire, David; Shaw, Willard

    2007-12-01

    Seven years ago, the removal of taxes and tariffs on insecticide treated nets (ITNs) was considered one of the easiest resolutions for most countries to implement among the targets agreed upon at the African Summit on Roll Back Malaria in Abuja, Nigeria, on April 25, 2000. However, seven years later, 24 of the 39 Abuja signatories continue to impose taxes and tariffs on this life-saving tool. Taxes and tariffs significantly increase the price of an insecticide treated net, reduce affordability, and discourage the commercial sector from importing insecticide treated net products. Consequently, Roll Back Malaria partners are engaged in advocacy efforts to remove taxes and tariffs on insecticide treated nets in malaria-endemic countries of Africa. This viewpoint summarizes key obstacles to the removal of taxes and tariffs that have been identified through a review of country situations. To achieve the goal of producing and supplying more than 160 million insecticide treated nets needed to reach the revised Roll Back Malaria Partnership targets by 2010, tax and tariff reforms are urgently needed. Such reforms must be accompanied by country-specific systems to protect the poor (e.g., through voucher systems for vulnerable groups and other forms of targeted subsidies). PMID:18165497

  17. Insecticidal toxins from black widow spider venom

    PubMed Central

    Rohou, A.; Nield, J.; Ushkaryov, Y.A.

    2007-01-01

    The biological effects of Latrodectus spider venom are similar in animals from different phyla, but these symptoms are caused by distinct phylum-specific neurotoxins (collectively called latrotoxins) with molecular masses ranging from 110 to 140 kDa. To date, the venom has been found to contain five insecticidal toxins, termed α, β, γ, δ and ε-latroinsectotoxins (LITs). There is also a vertebrate-specific neurotoxin, α-latrotoxin (α-LTX), and one toxin affecting crustaceans, α-latrocrustatoxin (α-LCT). These toxins stimulate massive release of neurotransmitters from nerve terminals and act (1) by binding to specific receptors, some of which mediate an exocytotic signal, and (2) by inserting themselves into the membrane and forming ion-permeable pores. Specific receptors for LITs have yet to be identified, but all three classes of vertebrate receptors known to bind α-LTX are also present in insects. All LTXs whose structures have been elucidated (α-LIT, δ-LIT, α-LTX and α-LCT) are highly homologous and have a similar domain architecture, which consists of a unique N-terminal sequence and a large domain composed of 13–22 ankyrin repeats. Three-dimensional (3D) structure analysis, so far done for α-LTX only, has revealed its dimeric nature and an ability to form symmetrical tetramers, a feature probably common to all LTXs. Only tetramers have been observed to insert into membranes and form pores. A preliminary 3D reconstruction of a δ-LIT monomer demonstrates the spatial similarity of this toxin to the monomer of α-LTX. PMID:17210168

  18. Influence of Pyrethroid Insecticides on Sodium and Calcium Influx in Neocortical Neurons

    EPA Science Inventory

    Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Using murine neocortical neurons in primary culture, we have compared the ability of 11 structurally diverse pyrethroid insecticides to evoke Na+ ...

  19. Evaluation of toxicity of selected insecticides against thrips on cotton in laboratory bioassays

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult vial technique (AVT) and spray table bioassays were conducted to evaluate toxicity of selected insecticides against immature and adult Western flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). In AVT, technical insecticides comprising of organophosphates (d...

  20. Resistance to bio-insecticides or how to enhance their sustainability: a review.

    PubMed

    Siegwart, Myriam; Graillot, Benoit; Blachere Lopez, Christine; Besse, Samantha; Bardin, Marc; Nicot, Philippe C; Lopez-Ferber, Miguel

    2015-01-01

    After more than 70 years of chemical pesticide use, modern agriculture is increasingly using biological control products. Resistances to conventional insecticides are wide spread, while those to bio-insecticides have raised less attention, and resistance management is frequently neglected. However, a good knowledge of the limitations of a new technique often provides greater sustainability. In this review, we compile cases of resistance to widely used bio-insecticides and describe the associated resistance mechanisms. This overview shows that all widely used bio-insecticides ultimately select resistant individuals. For example, at least 27 species of insects have been described as resistant to Bacillus thuringiensis toxins. The resistance mechanisms are at least as diverse as those that are involved in resistance to chemical insecticides, some of them being common to bio-insecticides and chemical insecticides. This analysis highlights the specific properties of bio-insecticides that the scientific community should use to provide a better sustainability of these products. PMID:26150820

  1. Resistance to bio-insecticides or how to enhance their sustainability: a review

    PubMed Central

    Siegwart, Myriam; Graillot, Benoit; Blachere Lopez, Christine; Besse, Samantha; Bardin, Marc; Nicot, Philippe C.; Lopez-Ferber, Miguel

    2015-01-01

    After more than 70 years of chemical pesticide use, modern agriculture is increasingly using biological control products. Resistances to conventional insecticides are wide spread, while those to bio-insecticides have raised less attention, and resistance management is frequently neglected. However, a good knowledge of the limitations of a new technique often provides greater sustainability. In this review, we compile cases of resistance to widely used bio-insecticides and describe the associated resistance mechanisms. This overview shows that all widely used bio-insecticides ultimately select resistant individuals. For example, at least 27 species of insects have been described as resistant to Bacillus thuringiensis toxins. The resistance mechanisms are at least as diverse as those that are involved in resistance to chemical insecticides, some of them being common to bio-insecticides and chemical insecticides. This analysis highlights the specific properties of bio-insecticides that the scientific community should use to provide a better sustainability of these products. PMID:26150820

  2. Efficacy of an insecticide paint against insecticide-susceptible and resistant mosquitoes - Part 1: Laboratory evaluation

    PubMed Central

    2010-01-01

    Background The main malaria vector Anopheles gambiae and the urban pest nuisance Culex quinquefasciatus are increasingly resistant to pyrethroids in many African countries. There is a need for new products and strategies. Insecticide paint Inesfly 5A IGR™, containing two organophosphates (OPs), chlorpyrifos and diazinon, and insect growth regulator (IGR), pyriproxyfen, was tested under laboratory conditions for 12 months following WHOPES Phase I procedures. Methods Mosquitoes used were laboratory strains of Cx. quinquefasciatus susceptible and resistant to OPs. The paint was applied at two different doses (1 kg/6 m2 and 1 kg/12 m2) on different commonly used surfaces: porous (cement and stucco) and non-porous (softwood and hard plastic). Insecticide efficacy was studied in terms of delayed mortality using 30-minute WHO bioassay cones. IGR efficacy on fecundity, fertility and larval development was studied on OP-resistant females exposed for 30 minutes to cement treated and control surfaces. Results After treatment, delayed mortality was high (87-100%) even against OP-resistant females on all surfaces except cement treated at 1 kg/12 m2. Remarkably, one year after treatment delayed mortality was 93-100% against OP-resistant females on non-porous surfaces at both doses. On cement, death rates were low 12 months after treatment regardless of the dose and the resistance status. Fecundity, fertility and adult emergence were reduced after treatment even at the lower dose (p < 10-3). A reduction in fecundity was still observed nine months after treatment at both doses (p < 10-3) and adult emergence was reduced at the higher dose (p < 10-3). Conclusions High mortality rates were observed against laboratory strains of the pest mosquito Cx. quinquefasciatus susceptible and resistant to insecticides. Long-term killing remained equally important on non-porous surfaces regardless the resistance status for over 12 months. The paint's effect on fecundity, fertility and adult

  3. Modeling the integration of parasitoid, insecticide, and transgenic insecticidal crop for the long-term control of an insect pest.

    PubMed

    Onstad, David W; Liu, Xiaoxia; Chen, Mao; Roush, Rick; Shelton, Anthony M

    2013-06-01

    The tools of insect pest management include host plant resistance, biological control, and insecticides and how they are integrated will influence the durability of each. We created a detailed model of the population dynamics and population genetics of the diamondback moth, Plutella xylostella L., and its parasitoid, Diadegma insulare (Cresson), to study long-term pest management in broccoli Brassica oleracea L. Given this pest's history of evolving resistance to various toxins, we also evaluated the evolution of resistance to transgenic insecticidal Bt broccoli (expressing Cry1Ac) and two types of insecticides. Simulations demonstrated that parasitism provided the most reliable, long-term control of P. xylostella populations. Use of Bt broccoli with a 10% insecticide-free refuge did not reduce the long-term contribution of parasitism to pest control. Small refuges within Bt broccoli fields can delay evolution of resistance > 30 generations if resistance alleles are rare in the pest population. However, the effectiveness of these refuges can be compromised by insecticide use. Rainfall mortality during the pest's egg and neonate stages significantly influences pest control but especially resistance management. Our model results support the idea that Bt crops and biological control can be integrated in integrated pest management and actually synergistically support each other. However, the planting and maintenance of toxin-free refuges are critical to this integration. PMID:23865173

  4. Microgeographical study of insecticide resistance in Triatoma infestans from Argentina.

    PubMed

    Germano, Mónica D; Picollo, María Inés; Mougabure-Cueto, Gastón A

    2013-12-01

    Chagas disease is a chronic parasitic infection restricted to America where it is currently estimated that 90 million people are at risk of acquiring the infection. Chemical control with pyrethroid insecticides has been effective to reduce disease transmission in several areas of the Southern Cone, although insecticide resistance has evolved and diminished the campaigns' results. Considering previous reports on the different levels of resistance between Triatoma infestans from different geographical areas, the objective of this work was to determine if T. infestans populations are toxicologically structured within localities. Response to the insecticide was measured and compared between houses of two Argentine localities. Different toxicity of deltamethrin was detected between dwellings of Chaco province, accounting for both susceptible and resistant houses within the same locality. However no difference was found among houses of Salta province. The results obtained in this work suggest that geographical structure is present not only at the between localities level, but also at the microgeograhical level. PMID:23962389

  5. Insects, Insecticides and Hormesis: Evidence and Considerations for Study

    PubMed Central

    Cutler, G. Christopher

    2013-01-01

    Insects are ubiquitous, crucial components of almost all terrestrial and fresh water ecosystems. In agricultural settings they are subjected to, intentionally or unintentionally, an array of synthetic pesticides and other chemical stressors. These ecological underpinnings, the amenability of insects to laboratory and field experiments, and our strong knowledgebase in insecticide toxicology, make the insect-insecticide model an excellent one to study many questions surrounding hormesis. Moreover, there is practical importance for agriculture with evidence of pest population growth being accelerated by insecticide hormesis. Nevertheless, insects have been underutilized in studies of hormesis. Where hormesis hypotheses have been tested, results clearly demonstrate stimulatory effects on multiple taxa as measured through several biological endpoints, both at individual and population levels. However, many basic questions are outstanding given the myriad of chemicals, responses, and ecological interactions that are likely to occur. PMID:23930099

  6. Validation of the Target Protein of Insecticidal Dihydroagarofuran Sesquiterpene Polyesters

    PubMed Central

    Lu, Lina; Qi, Zhijun; Li, Qiuli; Wu, Wenjun

    2016-01-01

    A series of insecticidal dihydroagarofuran sesquiterpene polyesters were isolated from the root bark of Chinese bittersweet (Celastrus angulatus Max). A previous study indicated that these compounds affect the digestive system of insects, and aminopeptidase N3 and V-ATPase have been identified as the most putative target proteins by affinity chromatography. In this study, the correlation between the affinity of the compounds to subunit H and the insecticidal activity or inhibitory effect on the activity of V-ATPase was analyzed to validate the target protein. Results indicated that the subunit H of V-ATPase was the target protein of the insecticidal compounds. In addition, the possible mechanism of action of the compounds was discussed. The results provide new ideas for developing pesticides acting on V-ATPase of insects. PMID:26999207

  7. Optimal Cotton Insecticide Application Termination Timing: A Meta-Analysis.

    PubMed

    Griffin, T W; Zapata, S D

    2016-08-01

    The concept of insecticide termination timing is generally accepted among cotton (Gossypium hirsutum) researchers; however, exact timings are often disputed. Specifically, there is uncertainty regarding the last economic insecticide application to control fruit-feeding pests including tarnished plant bug (Lygus lineolaris (Palisot de Beauvois)), boll weevil (Anthonomus grandis), bollworm (Helicoverpa zea), tobacco budworm (Heliothis virescens), and cotton fleahopper (Pseudatomoscelis seriatus). A systematic review of prior studies was conducted within a meta-analytic framework. Nine publicly available articles were amalgamated to develop an optimal timing principle. These prior studies reported 53 independent multiple means comparison field experiments for a total of 247 trial observations. Stochastic plateau theory integrated with econometric meta-analysis methodology was applied to the meta-database to determine the shape of the functional form of both the agronomic optimal insecticide termination timing and corresponding yield potential. Results indicated that current university insecticide termination timing recommendations are later than overall estimated timing suggested. The estimated 159 heat units (HU) after the fifth position above white flower (NAWF5) was found to be statistically different than the 194 HU termination used as the status quo recommended termination timing. Insecticides applied after 159 HU may have been applied in excess, resulting in unnecessary economic and environmental costs. Empirical results also suggested that extending the insecticide termination time by one unit resulted in a cotton lint yield increase of 0.27 kilograms per hectare up to the timing where the plateau began. Based on economic analyses, profit-maximizing producers may cease application as soon as 124 HU after NAWF5. These results provided insights useful to improve production systems by applying inputs only when benefits were expected to be in excess of the

  8. Novel AChE Inhibitors for Sustainable Insecticide Resistance Management

    PubMed Central

    Alout, Haoues; Labbé, Pierrick; Berthomieu, Arnaud; Djogbénou, Luc; Leonetti, Jean-Paul; Fort, Philippe; Weill, Mylène

    2012-01-01

    Resistance to insecticides has become a critical issue in pest management and it is particularly chronic in the control of human disease vectors. The gravity of this situation is being exacerbated since there has not been a new insecticide class produced for over twenty years. Reasoned strategies have been developed to limit resistance spread but have proven difficult to implement in the field. Here we propose a new conceptual strategy based on inhibitors that preferentially target mosquitoes already resistant to a currently used insecticide. Application of such inhibitors in rotation with the insecticide against which resistance has been selected initially is expected to restore vector control efficacy and reduce the odds of neo-resistance. We validated this strategy by screening for inhibitors of the G119S mutated acetylcholinesterase-1 (AChE1), which mediates insensitivity to the widely used organophosphates (OP) and carbamates (CX) insecticides. PyrimidineTrione Furan-substituted (PTF) compounds came out as best hits, acting biochemically as reversible and competitive inhibitors of mosquito AChE1 and preferentially inhibiting the mutated form, insensitive to OP and CX. PTF application in bioassays preferentially killed OP-resistant Culex pipiens and Anopheles gambiae larvae as a consequence of AChE1 inhibition. Modeling the evolution of frequencies of wild type and OP-insensitive AChE1 alleles in PTF-treated populations using the selectivity parameters estimated from bioassays predicts a rapid rise in the wild type allele frequency. This study identifies the first compound class that preferentially targets OP-resistant mosquitoes, thus restoring OP-susceptibility, which validates a new prospect of sustainable insecticide resistance management. PMID:23056599

  9. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  10. New Insecticides and Repellents For Use on Mosquitoes and Sand Flies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The major emphasis of our research is on the discovery and development of new insecticides for personal protection. The insecticide discovery effort involves structure-activity modeling to correlate molecular structure and electronic properties with repellent and/or insecticidal activity. Models a...

  11. Toxicity of selected insecticides to onion thrips (Thysanoptera: Thripidae) using a glass-vial bioassay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), are important pests that are primarily controlled with insecticides on both onions and cotton in the Lower Rio Grande Valley of Texas. Resistance to various insecticides has been reported so data are needed on toxicity of insecticides r...

  12. Adult vial bioassays of insecticidal toxicity against cotton fleahopper, Pseudatomoscelis seriatus (Reuter) (Hemiptera: Miridae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glass vials coated with several technical insecticides were used to determine the contact toxicity of insecticides on adult laboratory-reared and field-collected cotton fleahopper, Pseudatomoscelis seriatus (Reuter). For the 17 insecticides evaluated for laboratory-reared cotton fleahoppers, bifent...

  13. Haematological parameters as bioindicators of insecticide exposure in teleosts.

    PubMed

    Singh, Narendra Nath; Srivastava, Anil Kumar

    2010-06-01

    Haematological parameters, such as erythrocyte and leucocyte count, erythrocyte indices and thrombocyte number vis-a-vis coagulation of blood has been considered bioindicators of toxicosis in fish following exposure to organochlorine, organophosphate, carbamate and pyrethroid insecticides. This review deals with the effects of insecticides on the morphology of red blood cells, total erythrocyte count, haemoglobin content, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, erythrocyte sedimentation rate, total and differential leucocyte counts, thrombocyte count and clotting time in the peripheral blood of a number of teleosts. The review also takes stock of knowledge of the subject and explores prospects of additional research in the related area. PMID:20177774

  14. Insecticide applications to soil contribute to the development of Burkholderia mediating insecticide resistance in stinkbugs.

    PubMed

    Tago, Kanako; Kikuchi, Yoshitomo; Nakaoka, Sinji; Katsuyama, Chie; Hayatsu, Masahito

    2015-07-01

    Some soil Burkholderia strains are capable of degrading the organophosphorus insecticide, fenitrothion, and establish symbiosis with stinkbugs, making the host insects fenitrothion-resistant. However, the ecology of the symbiotic degrading Burkholderia adapting to fenitrothion in the free-living environment is unknown. We hypothesized that fenitrothion applications affect the dynamics of fenitrothion-degrading Burkholderia, thereby controlling the transmission of symbiotic degrading Burkholderia from the soil to stinkbugs. We investigated changes in the density and diversity of culturable Burkholderia (i.e. symbiotic and nonsymbiotic fenitrothion degraders and nondegraders) in fenitrothion-treated soil using microcosms. During the incubation with five applications of pesticide, the density of the degraders increased from less than the detection limit to around 10(6)/g of soil. The number of dominant species among the degraders declined with the increasing density of degraders; eventually, one species predominated. This process can be explained according to the competitive exclusion principle using V(max) and K(m) values for fenitrothion metabolism by the degraders. We performed a phylogenetic analysis of representative strains isolated from the microcosms and evaluated their ability to establish symbiosis with the stinkbug Riptortus pedestris. The strains that established symbiosis with R. pedestris were assigned to a cluster including symbionts commonly isolated from stinkbugs. The strains outside the cluster could not necessarily associate with the host. The degraders in the cluster predominated during the initial phase of degrader dynamics in the soil. Therefore, only a few applications of fenitrothion could allow symbiotic degraders to associate with their hosts and may cause the emergence of symbiont-mediated insecticide resistance. PMID:26059639

  15. A Zn based coordination polymer exhibiting long-lasting phosphorescence.

    PubMed

    Cepeda, Javier; Sebastian, Eider San; Padro, Daniel; Rodríguez-Diéguez, Antonio; García, Jose A; Ugalde, Jesus M; Seco, Jose M

    2016-07-01

    A new Zn(ii) based coordination polymer (CP) built by the cohesive pilling of 2D Shubnikov type layers is reported. This material exhibits time dependent multicoloured emission, part of which shows a persistent green phosphorescence visible for up to two seconds to the naked eye, which originates from multiple charge transfer mechanisms. PMID:27297330

  16. Lexical Inhibition and Sublexical Facilitation Are Surprisingly Long Lasting

    ERIC Educational Resources Information Center

    Sumner, Meghan; Samuel, Arthur G.

    2007-01-01

    When a listener hears a word (beef), current theories of spoken word recognition posit the activation of both lexical (beef) and sublexical (/b/, /i/, /f/) representations. No lexical representation can be settled on for an unfamiliar utterance (peef). The authors examined the perception of nonwords (peef) as a function of words or nonwords heard…

  17. Making Long-Lasting Changes with the Environment Rating Scales

    ERIC Educational Resources Information Center

    Harms, Thelma

    2010-01-01

    An assessment with the Environment Rating Scales (ERS) is designed to give early childhood administrators and teaching staff much more than a set of quality scores. Appropriately used, an ERS assessment can provide a blueprint for planning and carrying out both immediate and long-range program improvements. Unfortunately, programs often complete…

  18. LONG-LASTING LITHIUM NEUROTOXICITY IN AN ADOLESECENT

    PubMed Central

    Khanna, Rakesh; Sethi, Sujata

    1993-01-01

    SUMMARY Acute lithium intoxication is well known. A case of long tasting lithium neurotoxicity in an adolescent male is reported, who showed signs of cerebellar as well as brain stem involvement. Persistent lithium neurotoxicity is discussed and the recommendation made that this condition be considered irreversible only if no substantial recovery occurs in the first six months. PMID:21743620

  19. Dentofacial development in long-lasting nasal sten