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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 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

  12. 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

  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. 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

  4. 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

  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. 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

  8. 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

  9. 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

  10. 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

  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. 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

  15. 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

  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. 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

  3. 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

  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. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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.

  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. 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

  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

    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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  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. 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

  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. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  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 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  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. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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

  17. 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

  18. 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

  19. 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

  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. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  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. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  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. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  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. 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

  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

    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

  3. 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

  4. 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

  5. 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

  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. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  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. 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

  5. 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

  6. 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

  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. 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