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1.
Am J Trop Med Hyg ; 110(4): 731-737, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38412550

RESUMO

Dengue viruses (DENV) continue to cause large outbreaks in tropical countries, while chikungunya and Zika (ZIKV) viruses have added complexity to Aedes-borne disease prevention and control efforts. Because these viruses are transmitted by the same vectors in urban areas, it is useful to understand if sequential outbreaks caused by these viruses have commonalities, such as similar seasonal and spatial patterns, that would help anticipate and perhaps prevent future outbreaks. We explored and analyzed the heterogeneity of confirmed cases of DENV (2010-2014 and 2015-2022) and ZIKV (2016-2017) during outbreaks in the San Juan metropolitan area of Puerto Rico to explore their degree of overlap and prioritize areas for Aedes aegypti control. Deidentified, georeferenced case data were aggregated into grid cells (500 × 500 m) within a geographical information system of the study area and analyzed to calculate the degree of overlap between outbreaks. Spatial autocorrelations using local indicators of spatial associations were conducted to identify significant disease case hot spots and correlations between outbreaks. We found that 75% of cases during the three transmission periods were concentrated in 25% of the total number of grid cells covering the study area. We also found significant clustering of cases during each outbreak, enabling identification of consistent disease hot spots. Our results showed 85% spatial overlap between cases of ZIKV in 2015-2017 and DENV in 2010-2014 and 97% overlap between DENV cases in 2010-2014 and 2015-2022. These results reveal urban areas at greater risk of future arbovirus outbreaks that should be prioritized for vector control.


Assuntos
Aedes , Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Animais , Humanos , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Porto Rico/epidemiologia , Mosquitos Vetores , Dengue/epidemiologia , Dengue/prevenção & controle
2.
J Med Entomol ; 60(4): 796-807, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37156093

RESUMO

We investigated the effects of interannual El Niño Southern Oscillation (ENSO) events on local weather, Aedes aegypti populations, and combined cases of dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) viruses in 2 communities with mass mosquito trapping and 2 communities without mosquito control in southern Puerto Rico (2013-2019). Gravid adult Ae. aegypti populations were monitored weekly using Autocidal Gravid Ovitraps (AGO traps). Managing Ae. aegypti populations was done using 3 AGO traps per home in most homes. There were drought conditions in 2014-2015 concurrent with the emergence of a strong El Niño (2014-2016), wetter conditions during La Niña (2016-2018), a major hurricane (2017), and a weaker El Niño (2018-2019). The main factor explaining differences in Ae. aegypti abundance across sites was mass trapping. Populations of Ae. aegypti reached maximum seasonal values during the wetter and warmer months of the year when arbovirus epidemics occurred. El Niño was significantly associated with severe droughts that did not impact the populations of Ae. aegypti. Arbovirus cases at the municipality level were positively correlated with lagged values (5-12 mo.) of the Oceanic El Niño Index (ONI), droughts, and abundance of Ae. aegypti. The onset of strong El Niño conditions in Puerto Rico may be useful as an early warning signal for arboviral epidemics in areas where the abundance of Ae. aegypti exceeds the mosquito density threshold value.


Assuntos
Aedes , Infecção por Zika virus , Zika virus , Animais , Porto Rico/epidemiologia , El Niño Oscilação Sul , Tempo (Meteorologia) , Mosquitos Vetores
3.
J Tissue Eng ; 13: 20417314221119615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093431

RESUMO

Chronic wounds in type-2 diabetic patients present areas of severe local skin ischemia despite mostly normal blood flow in deeper large arteries. Therefore, restoration of blood perfusion requires the opening of arterial connections from the deep vessels to the superficial skin layer, that is, arteriogenesis. Arteriogenesis is regulated differently from microvascular angiogenesis and is optimally stimulated by high doses of Vascular Endothelial Growth Factor-A (VEGF) together with Platelet-Derived Growth Factor-BB (PDGF-BB). Here we found that fibrin hydrogels decorated with engineered versions of VEGF and PDGF-BB proteins, to ensure protection from degradation and controlled delivery, efficiently accelerated wound closure in diabetic and obese db/db mice, promoting robust microvascular growth and a marked increase in feeding arterioles. Notably, targeting the arteriogenic factors to the intact arterio-venous networks in the dermis around the wound was more effective than the routine treatment of the inflamed wound bed. This approach is readily translatable to a clinical setting.

4.
Curr Opin Insect Sci ; 52: 100942, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35667560

RESUMO

Aedes aegypti, the main vector of dengue, chikungunya, and Zika viruses uses artificial containers around homes to undergo immature development, making household-level detection and control extremely difficult in large urban areas. Mass trapping is an emerging methodology to control container-Aedes species such as Aedes aegypti and Aedes albopictus because effective traps for adult stages of these mosquitoes were developed recently. There are three main approaches to mass-trapping these mosquitoes: 1) Pull (attract/kill), 2) push (repel)-pull (attract/kill), and 3) pull (attract/contaminate/infect)-push (fly away). Effective mass-trapping depends on trap quality (capture efficiency, sturdiness, frequency of servicing), trap density and areal coverage, community involvement, and safety. Recent studies showed that Ae. aegypti populations can be sustainably controlled by mass trapping, although more area-wide studies showing effectiveness at preventing disease are needed for all trapping systems. Cost-effectiveness studies are needed for all emerging Aedes control approaches.


Assuntos
Aedes , Vírus da Dengue , Infecção por Zika virus , Zika virus , Animais , Mosquitos Vetores , Infecção por Zika virus/prevenção & controle
5.
J Am Mosq Control Assoc ; 38(1): 19-23, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35276724

RESUMO

We monitored trap captures of Culex quinquefasciatus using an interrupted time-series study to determine if autocidal gravid ovitraps (AGO traps) were useful to control the population of this mosquito species in a community in southern Puerto Rico. Data for this report came from a previous study in which we used mass trapping to control Aedes aegypti, resulting in a significant 79% reduction in numbers of this species. The AGO traps used to monitor and control Ae. aegypti also captured numerous Cx. quinquefasciatus. Culex quinquefasciatus was monitored in surveillance AGO traps from October 2011 to February 2013, followed by a mosquito control intervention from February 2013 to June 2014. Optimal captures of this mosquito occurred on the 2nd wk after the traps were set or serviced, which happened every 8 wk. Changes in collection numbers of Cx. quinquefasciatus were positively correlated with rainfall and showed oscillations every 8 wk, as revealed by sample autocorrelation analyses. Culex quinquefasciatus was attracted to and captured by AGO traps, so mass trapping caused a significant but moderate reduction of the local population (31.2%) in comparison with previous results for Ae. aegypti, possibly resulting from female mosquitoes flying in from outside of the study area and decreased attraction to the traps past the 2nd wk of trap servicing. Because Ae. aegypti and Cx. quinquefasciatus are frequently established in urban areas, mass trapping to control the former has some impact on Cx. quinquefasciatus. Control of the latter could be improved by locating and treating its aquatic habitats within and around the community.


Assuntos
Aedes , Culex , Animais , Ecossistema , Feminino , Controle de Mosquitos/métodos , Porto Rico
6.
Trop Med Int Health ; 27(3): 300-309, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35118778

RESUMO

OBJECTIVE: To investigate the presence and abundance of mosquito species in containers found in different types of cemeteries in Puerto Rico to assess their importance and make control recommendations. METHODS: We conducted surveys of containers with water in 16 cemeteries in southeastern Puerto Rico to detect the presence of larvae and pupae of Aedes aegypti and other mosquitoes; to identify the most common and productive containers and to study their variation in relation to the type of cemetery. RESULTS: The most common containers with water were flowerpots, followed in abundance by a variety of discarded containers and open tombs. We found a positive relationship between density of containers with water and rainfall. There was a rich community of mosquito species developing in containers of the inspected cemeteries: nine mosquito species belonging to four genera with Ae. aegypti and Ae. mediovittatus being the most frequent and abundant. We sampled 13 cement-type cemeteries, 2 mixed and only 1 lawn cemetery, consequently, we could not draw any conclusion regarding container productivity and cemetery type. CONCLUSIONS: Surveyed cemeteries were important sources of Ae. aegypti and other mosquitoes in flowerpots, discarded containers and open tombs. We recommend conducting further studies to establish how frequently inspections should occur; and mosquito control by emptying aquatic habitats and larviciding to reduce mosquito productivity and protect workers and visitors from mosquito bites and possible transmission of arboviruses.


Assuntos
Aedes , Animais , Cemitérios , Ecossistema , Humanos , Larva , Controle de Mosquitos , Mosquitos Vetores , Porto Rico , Pupa , Água
7.
J Med Entomol ; 59(1): 314-319, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34536077

RESUMO

Mass-trapping has been used to control outbreaks of Aedes aegypti (Linnaeus) (Diptera: Culicidae) in Puerto Rico since 2011. We investigated the effect of multi-year, insecticide-free mass trapping had on the insecticide susceptibility profile of Ae. aegypti. Eggs collected in southern Puerto Rico were used to generate F1 populations that were tested for susceptibility to permethrin, sumethrin, bifenthrin, deltamethrin, and malathion according to CDC bottle bioassays protocols. All populations of Ae. aegypti were resistant to the synthetic pyrethroids and mosquitoes from two locations were partially resistant to malathion. Population genetic analysis, using a double digest restriction sites associated DNA sequencing (ddRADseq) approach, indicated a large amount of migration between study sites effectively homogenizing the mosquito populations. Mass-trapping using noninsecticidal autocidal gravid ovitraps did not restore susceptibility to five active ingredients that are found in commercial insecticides. Migration between communities was high and would have brought outside alleles, including resistant alleles to the treatment communities. Further investigation suggests that household use of commercially available insecticide products may continue to select for resistance in absence of public health space spraying of insecticides.


Assuntos
Aedes , Genética Populacional , Resistência a Inseticidas/genética , Aedes/efeitos dos fármacos , Aedes/genética , Distribuição Animal , Animais , Genes de Insetos , Inseticidas/farmacologia , Malation/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/genética , Permetrina/farmacologia , Porto Rico , Piretrinas/farmacologia
8.
PLoS Negl Trop Dis ; 15(12): e0009966, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34871301

RESUMO

Arboviral diseases transmitted by Aedes species mosquitoes pose an increasing public health challenge in tropical regions. Wolbachia-mediated population suppression (Wolbachia suppression) is a vector control method used to reduce Aedes mosquito populations by introducing male mosquitoes infected with Wolbachia, a naturally occurring endosymbiotic bacterium. When Wolbachia-infected male mosquitoes mate with female wild mosquitoes, the resulting eggs will not hatch. Public support is vital to the successful implementation and sustainability of vector control interventions. Communities Organized to Prevent Arboviruses (COPA) is a cohort study to determine the incidence of arboviral disease in Ponce, Puerto Rico and evaluate vector control methods. Focus groups were conducted with residents of COPA communities to gather their opinion on vector control methods; during 2018-2019, adult COPA participants were interviewed regarding their views on Wolbachia suppression; and a follow-up questionnaire was conducted among a subset of participants and non-participants residing in COPA communities. We analyzed factors associated with support for this method. Among 1,528 participants in the baseline survey, median age was 37 years and 63% were female. A total of 1,032 (68%) respondents supported Wolbachia suppression. Respondents with an income of $40,000 or more were 1.34 times as likely [95% CI: 1.03, 1.37] to support Wolbachia suppression than those who earned less than $40,000 annually. Respondents who reported repellant use were 1.19 times as likely to support Wolbachia suppression [95% CI: 1.03, 1.37]. A follow-up survey in 2020 showed that most COPA participants (86%) and non-participants living in COPA communities (84%) supported Wolbachia suppression during and after an educational campaign. The most frequent questions regarding this method were related to its impact on human and animal health, and the environment. Continuous community engagement and education efforts before and during the implementation of novel vector control interventions are necessary to increase and maintain community support.


Assuntos
Aedes/microbiologia , Controle de Mosquitos/métodos , Mosquitos Vetores/microbiologia , Wolbachia/fisiologia , Adulto , Aedes/fisiologia , Animais , Estudos de Coortes , Apoio Comunitário/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/fisiologia , Comportamento Sexual Animal , Inquéritos e Questionários , Adulto Jovem
9.
Front Bioeng Biotechnol ; 9: 688467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277588

RESUMO

Non-healing ulcers are a serious complication of diabetes mellitus and a major unmet medical need. A major cause for the lack of healing is the impairment of spontaneous vascularization in the skin, despite mostly normal blood flow in deeper large vessels. Therefore, pro-angiogenic treatments are needed to increase therapeutic perfusion by recruiting new arterial connections (therapeutic arteriogenesis). Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis in physiology and disease, but exploitation of its therapeutic potential requires careful control of its dose distribution in tissue. Co-delivery of platelet derived growth factor-BB (PDGF-BB) has been shown to expand the therapeutic window of VEGF and also improve associated arteriogenesis. We used a highly controlled protein delivery system, based on a clinically applicable fibrin-based platform, to investigate the angiogenic and arteriogenic potential of engineered versions (TG-) of VEGF and PDGF-BB proteins in the skin of diabetic and obese db/db mice. Intradermal delivery of therapeutically relevant doses of TG-VEGF and TG-PDGF-BB induced robust growth of new microvascular networks with similar efficacy as in normal littermate control mice. Further, TG-PDGF-BB prevented the formation of aberrant vascular enlargements by high TG-VEGF levels. As fibrin was degraded after the first week, the induced angiogenesis mostly regressed by 4 weeks, but it promoted effective arteriogenesis in the dermal layer. Therefore, controlled co-delivery of TG-VEGF and TG-PDGF-BB recombinant proteins is effective to induce angiogenesis and arteriogenesis in diabetic mouse skin and should be further investigated to promote diabetic wound healing.

10.
J Am Mosq Control Assoc ; 37(2): 61-67, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34184049

RESUMO

Gravid traps that collect eggs or adult mosquitoes use color, size, or volume as well as water or plant infusions as attractants. Biorational larvicides have been used to prevent these devices from producing adult mosquitoes within the traps. Results from field assays on the use of several biorational larvicides for various mosquito species have provided mixed results in terms of increased, neutral, or reduced attraction. We investigated the use of Bacillus thuringiensis var. israelensis, spinosad, and novaluron in field assays in Puerto Rico to evaluate the behavioral response of Aedes aegypti and Culex spp. to autocidal gravid ovitraps (AGO traps). The purpose of the study was to increase the safety of these traps by preventing accidental release of adult mosquitoes when traps are opened or damaged. We also investigated whether trap color (blue, green, terracotta) that may be more amenable for use by residents in their properties induced a similar attraction response to the original black trap color. We found that the use of biorational larvicides did not significantly change the behavioral attraction of these mosquito species to AGO traps. For Ae. aegypti, green traps yielded the lowest captures while black, terracotta, and blue produced similar higher yields. Culex spp. in black traps showed significantly higher captures compared with other colors. These results suggest that black, terracotta, or blue AGO traps can be used for the surveillance and control of Ae. aegypti.


Assuntos
Aedes , Culex , Animais , Controle de Mosquitos , Porto Rico , Fosfatase Ácida Resistente a Tartarato
11.
Am J Trop Med Hyg ; 104(1): 145-150, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021195

RESUMO

The control of container Aedes species by house inspections usually achieves insufficient coverage and impact because a percentage of residents are absent and some residents refuse inspections and treatments. In addition, another fraction of the buildings may be uninhabited, such as those for rent or sale, or abandoned. Although the productivity of Aedes aegypti has been investigated in abandoned lots, less is known about the importance of uninhabited buildings. We investigated Ae. aegypti pupal productivity in inhabited, vacant, and abandoned houses and its interaction with socioeconomic levels (SELs). We found pupae in containers of 386 houses (66 abandoned, 62 vacant, and 258 inhabited) in 19 neighborhoods in southern Puerto Rico from May to August 2017. Using a generalized linear model, we found a significant interaction between the status of the house (abandoned, vacant, and inhabited) and SELs (low, medium) on Ae. aegypti pupal abundance. More pupae were found in abandoned and inhabited houses of low SELs. The lowest productivity was found in vacant houses, regardless of the SEL. Most containers producing Ae. aegypti in low-SEL houses were discarded on backyards, whereas in medium SELs, most productivity came from containers in use. Septic tanks producing Ae. aegypti were found only in houses of low SELs, where most emerging mosquitoes came from inhabited houses. We did not find any pupae of Ae. aegypti on roofs. These results indicate that proper yard management could significantly reduce the production of Ae. aegypti and the risk of dengue infections in low-SEL neighborhoods.


Assuntos
Aedes , Utensílios Domésticos , Habitação , Animais , Humanos , Controle de Mosquitos/métodos , Mosquitos Vetores , Porto Rico
12.
MMWR Morb Mortal Wkly Rep ; 69(28): 938-940, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32673302

RESUMO

Mosquitoborne disease outbreaks occur every year in the United States from one or more of the arboviral diseases dengue, West Nile, LaCrosse, Eastern equine encephalitis, and Zika (1). Public opinion communicated through traditional and social media and the Internet, competing public health and resource priorities, and local conditions can impede the ability of vector control organizations to prevent and respond to outbreaks of mosquitoborne disease. The Environmental Protection Agency (EPA) and CDC performed a coordinated review of the concerns and challenges associated with continuation of mosquito surveillance and control during public health emergencies and disasters. This report highlights the first joint recommendation from EPA and CDC. Mosquito surveillance and control should be maintained by state and local mosquito control organizations to the extent that local conditions and resources will allow during public health emergencies and natural disasters. Integrated pest management (IPM) is the best approach for mosquito control (2). IPM uses a combination of methods, including both physical and chemical means of control (3). For chemical means of control, CDC and EPA recommend the use of larvicides and adulticides following the EPA label. It is imperative that public health recommendations be followed to ensure the safety of the pesticide applicator and the public.


Assuntos
Surtos de Doenças , Monitoramento Ambiental , Controle de Mosquitos/organização & administração , Desastres Naturais , Centers for Disease Control and Prevention, U.S. , Humanos , Estados Unidos/epidemiologia , United States Environmental Protection Agency
13.
Cell Metab ; 31(6): 1136-1153.e7, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32492393

RESUMO

Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Mechanistically, loss of pfkfb3 reduced lactate secretion by ECs and lowered lactate levels in the ischemic muscle. Addition of lactate to pfkfb3-deficient ECs restored M2-like polarization in an MCT1-dependent fashion. Lactate shuttling by ECs enabled macrophages to promote proliferation and fusion of muscle progenitors. Moreover, VEGF production by lactate-polarized macrophages was increased, resulting in a positive feedback loop that further stimulated angiogenesis. Finally, increasing lactate levels during ischemia rescued macrophage polarization and improved muscle reperfusion and regeneration, whereas macrophage-specific mct1 deletion prevented M2-like polarization. In summary, ECs exploit glycolysis for angiocrine lactate shuttling to steer muscle regeneration from ischemia.


Assuntos
Células Endoteliais/química , Isquemia/metabolismo , Lactatos/farmacologia , Macrófagos/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Animais , Células Cultivadas , Isquemia/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Músculo Esquelético/metabolismo
14.
Sci Rep ; 10(1): 6803, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321946

RESUMO

Aedes aegypti is the main vector of arboviral diseases such as dengue, chikungunya and Zika. A key feature for disease transmission modeling and vector control planning is adult mosquito dispersal. We studied Ae aegypti adult dispersal by conducting a mark-capture study of naturally occurring Ae. aegypti from discarded containers found along a canal that divided two residential communities in Donna, Texas, USA. Stable isotopes were used to enrich containers with either 13C or 15N. Adult mosquitoes were collected outdoors in the yards of households throughout the communities with BG Sentinel 2 traps during a 12-week period. Marked mosquito pools with stable isotopes were used to estimate the mean distance travelled using three different approaches (Net, Strip or Circular) and the probability of detecting an isotopically marked adult at different distances from the larval habitat of origin. We consistently observed, using the three approaches that male (Net: 220 m, Strip: 255 m, Circular: 250 m) Ae. aegypti dispersed further in comparison to gravid (Net: 135 m, Strip: 176 m, Circular: 189 m) and unfed females (Net: 192 m, Strip: 213 m, Circular: 198 m). We also observed that marked male capture probability slightly increased with distance, while, for both unfed and gravid females, such probability decreased with distance. Using a unique study design documenting adult dispersal from natural larval habitat, our results suggest that Ae. aegypti adults disperse longer distances than previously reported. These results may help guide local vector control authorities in their fight against Ae. aegypti and the diseases it transmits, suggesting coverage of 200 m for the use of insecticides and innovative vector control tools.


Assuntos
Isótopos de Carbono/metabolismo , Ecossistema , Meio Ambiente , Controle de Mosquitos/métodos , Isótopos de Nitrogênio/metabolismo , Algoritmos , Animais , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Feminino , Humanos , Inseticidas/farmacologia , Masculino , Modelos Teóricos , Controle de Mosquitos/instrumentação , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/metabolismo , Mosquitos Vetores/virologia , Texas , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
15.
Am J Trop Med Hyg ; 102(4): 869-875, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043443

RESUMO

A dengue outbreak occurred on Hawaii Island between September 2015 and March 2016. Entomological investigations were undertaken between December 2015 and February 2016 to determine which Aedes mosquito species were responsible for the outbreak. A total of 3,259 mosquitoes were collected using a combination of CDC autocidal gravid ovitraps, Biogents BG-Sentinel traps, and hand-nets; immature mosquitoes were collected during environmental surveys. The composition of species was Aedes albopictus (58%), Aedes aegypti (25%), Wyeomyia mitchelli (7%), Aedes vexans (5%), Culex quinquefasciatus (4%), and Aedes japonicus (1%). Adult mosquitoes were analyzed by real-time reverse transcription polymerase chain reaction (PCR) for the presence of dengue virus (DENV) RNA. Of the 185 pools of female mosquitoes tested, 15 containing Ae. albopictus were positive for the presence of DENV type 1 RNA. No virus was detected in pools of the remaining species. Phylogenetic analysis showed the virus strain belonged to genotype I and was closely related to strains that were circulating in the Pacific between 2008 and 2014. This is the first report of detection of DENV in Ae. albopictus from Hawaii.


Assuntos
Aedes/virologia , Vírus da Dengue/classificação , Dengue/epidemiologia , Dengue/virologia , Surtos de Doenças , Animais , Dengue/genética , Feminino , Havaí/epidemiologia , Humanos , Filogenia
16.
Stem Cells Transl Med ; 9(4): 433-444, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31922362

RESUMO

Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue-engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short-term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis.


Assuntos
Neovascularização Fisiológica , Medicina Regenerativa , Animais , Técnicas de Transferência de Genes , Humanos , Monócitos/citologia , Pericitos/citologia , Engenharia de Proteínas
17.
J Cereb Blood Flow Metab ; 40(2): 404-419, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30621518

RESUMO

The myoblast-mediated delivery of angiogenic genes represents a cell-based approach for targeted induction of therapeutic collateralization. Here, we tested the superiority of myoblast-mediated co-delivery of vascular endothelial growth factor-A (VEGF) together with platelet-derived growth factor-BB (PDGF-BB) on transpial collateralization of an indirect encephalomyosynangiosis (EMS) in a model of chronic cerebral ischemia. Mouse myoblasts expressing a reporter gene alone (empty vector), VEGF, PDGF-BB or VEGF and PDGF-BB through a single bi-cistronic vector (VIP) were implanted into the temporalis muscle of an EMS following permanent ipsilateral internal carotid artery occlusion in adult, male C57BL/6N mice. Over 84 days, myoblast engraftment and gene product expression, hemodynamic impairment, transpial collateralization, angiogenesis, pericyte recruitment and post-ischemic neuroprotection were assessed. By day 42, animals that received PDGF-BB in combination with VEGF (VIP) showed superior hemodynamic recovery, EMS collateralization and ischemic protection with improved pericyte recruitment around the parenchymal vessels and EMS collaterals. Also, supplementation of PDGF-BB resulted in a striking astrocytic activation with intrinsic VEGF mobilization in the cortex below the EMS. Our findings suggest that EMS surgery together with myoblast-mediated co-delivery of VEGF/PDGF-BB may have the potential to serve as a novel treatment strategy for augmentation of collateral flow in the chronically hypoperfused brain.


Assuntos
Becaplermina , Isquemia Encefálica , Córtex Cerebral , Circulação Cerebrovascular , Vetores Genéticos , Mioblastos , Fator A de Crescimento do Endotélio Vascular , Animais , Becaplermina/biossíntese , Becaplermina/genética , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Doença Crônica , Masculino , Camundongos , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Mioblastos/transplante , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
18.
J Am Mosq Control Assoc ; 36(2): 66-73, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33647132

RESUMO

To improve detection and assessment of Aedes aegypti abundance, we investigated whether microhabitat factors of the location of autocidal gravid ovitraps (AGO traps) influenced captures of gravid females in 2 locations in southern Puerto Rico. One location had been under vector control for several years using mass AGO trapping (intervention site), where Ae. aegypti abundance was several times lower than in the other study site without mosquito control (nonintervention site). We observed 10 environmental factors describing trap microhabitat location, and monitored water volume and minimum, maximum, and average temperature in AGO traps. Air temperature, relative humidity, and rainfall were recorded at each site. We conducted a hot-spot analysis of AGO traps to understand whether trap captures were influenced by the local abundance of mosquitoes rather than or in addition to trap microhabitat factors. AGO traps were classified using a 2-step cluster analysis based on attributes of trap microhabitats, water temperature, and water volume. Captures of female Ae. aegypti in each cluster per site were compared between resulting clusters to determine whether trap microhabitat factors defining the clusters were associated with trap captures. Trap captures in both study sites were mostly correlated with captures in nearby traps regardless of trap microhabitat factors, possibly reflecting the influence of the spatial aggregation of mosquitoes coming from nearby aquatic habitats or the concentration of dispersing adults. These results indicated that AGO traps can be located at places that can be easily reached during periodic inspections, such as in front of houses, without much regard to local microhabitat conditions.


Assuntos
Aedes , Controle de Mosquitos/instrumentação , Animais , Meio Ambiente , Feminino , Masculino , Controle de Mosquitos/métodos , Densidade Demográfica , Porto Rico
19.
PLoS Negl Trop Dis ; 13(12): e0007988, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31877132

RESUMO

BACKGROUND: Detecting and monitoring the transmission of arboviruses such as Zika virus (ZIKV), dengue virus, and chikungunya virus is critical for prevention and control activities. Previous work has compared the ability of different human-focused surveillance strategies to detect ZIKV transmission in U.S. counties where no known transmission had occurred, but whether virological surveillance in mosquitoes could represent an effective surveillance system is unclear. OBJECTIVES: We leveraged a unique set of data from human and virological surveillance in Ae. aegypti during the 2016 ZIKV epidemic in Caguas, Puerto Rico, to compare alternative strategies for detecting and monitoring ZIKV activity. METHODS: We developed a simulation model for mosquito and human surveillance strategies and simulated different transmission scenarios with varying infection rates and mosquito trap densities. We then calculated the expected weekly number of detected infections, the probability of detecting transmission, and the number of tests needed and compared the simulations with observed data from Caguas. RESULTS: In simulated high transmission scenarios (1 infection per 1,000 people per week), the models demonstrated that both approaches had estimated probabilities of detection of greater than 78%. In simulated low incidence scenarios, vector surveillance had higher sensitivity than human surveillance and sensitivity increased with more traps, more trapping effort, and testing. In contrast, the actual data from Caguas indicated that human virological surveillance was more sensitive than vector virological surveillance during periods of both high and low transmission. CONCLUSION: In scenarios where human surveillance is not possible or when transmission intensity is very low, virological surveillance in Ae. aegypti may be able to detect and monitor ZIKV epidemic activity. However, surveillance for humans seeking care for Zika-like symptoms likely provides an equivalent or more sensitive indicator of transmission intensity in most circumstances.


Assuntos
Aedes/virologia , Transmissão de Doença Infecciosa/prevenção & controle , Monitoramento Epidemiológico , Mosquitos Vetores/virologia , Infecção por Zika virus/prevenção & controle , Zika virus/isolamento & purificação , Animais , Simulação por Computador , Feminino , Incidência , Porto Rico/epidemiologia , Sensibilidade e Especificidade , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão
20.
Emerg Infect Dis ; 25(10): 1959-1961, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31538919

RESUMO

In response to the 2016 Zika outbreak, Aedes aegypti mosquitoes from 38 locations across Puerto Rico were screened using Centers for Disease Control and Prevention bottle bioassays for sensitivity to insecticides used for mosquito control. All populations were resistant to pyrethroids. Naled, an organophosphate, was the most effective insecticide, killing all mosquitoes tested.


Assuntos
Aedes , Inseticidas , Controle de Mosquitos/métodos , Infecção por Zika virus/prevenção & controle , Animais , Feminino , Humanos , Resistência a Inseticidas , Naled , Porto Rico/epidemiologia
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