A pilot study to control Lutzomyia umbratilis (Diptera: Psychodidae), the major vector of Leishmania brazileiensis guyanensis, in a peri-urban rainforest of Manaus, Amazonas State, Brazil

In the second half of 1980, 112 (or ca. 16%) of the inhabitants of the new settlement of São José, city of Manaus, contracted cutaneous leishmaniasis whilst clearing their properties of terra firme rainforest. With the aid of SUCAM, the authors carried out a pilot study to investigate the feasibility of reducing populations of Lutzomyia umbratilis, the local silvatic vector of Leishmania braziliensis guyanensis, by spraying insecticide on its favoured diurnal resting sites, the bases of the larger forest trees. Most manvector contact is at these resting sites and, therefore, it was encouraging to record a marked reduction of the tree-base populations of L. umbratilis for 21 days following just one application of D.D.T. emulsion in an area 200m square. Most of the treated trunks were not occupied by L. umbratilis for at least eleven months. Suggestions for extending the pilot study are made, and the need for collaboration with a clinical team is emphasized. Leishmania b. guyanensis is the aetiological agent of [quot ]pain bois[quot ], which is hyperendemic from French Guiana to central Amazônia. In the absence of proven vaccines or methods of vector control, some simple methods for limiting transmission of Le. b. guyanensis to man are listed.

El "Status" taxonomico de leishmania garnhami, indicado por su patron de desarrollo en el Vector

Bajo condiciones experimentales, se estabelece el de desarrollo primario de Leishmania garnhami em su vector Lutzomyia townsendi, siguiendo disecciones diarias entre el Iro y 12mo dia post-imnfección. Se demuestra que L. garnhami puede lograr el estabelecimiento inicial de la infección en cualquiera de las regiones del intestino y en los túbulos de Malpighi del insecto vector. Un comportamiento similar fue observado en ejemplares de Lu. longipalpis. Se discute la susceptibilidad de Lu. townsendi a las infecciones por L. mexicana, L. braziliensis y L. garnhami. Se concluye que L. garnhami, a juzgar por su comportamiento en el vector, debe considerarse distinta a las especies del complejo L.mexicana y que su patrón de desarrollo difiere del de las especies de la Sección Suprapylaria, ya que invaden el triângulo pilórico, y del de la Peripylaria por su invasión a los túbulos de Malpighi.

Molluscicide activity of the "Avelós" plant (Euphorbia tirucalli, L. ) on Biomphalaria glabrata, the mollusc vector of schistosomiasis

An aqueous solution of the latex of Euphorbia tirucalli collected at sites receiving large amounts of sunlight showed molluscicide action on Biomphalaria glabrata, with LD50 obtained at the concentration of 28,0 ppm and LD90 at the concentration of 85,0 ppm. The toxicity of the product for fish was similar to that of Bayluscide and of copper sulfate used for comparison. However, the wide distribution of the plant, its easy propagation and the simple procedure for extraction of the active substance, which is biodegradable, favor "avelós" as a promising agent in the control of schistosomiasis.

Lutzomyia gasparviannai Martins, Godoy & Silva, 1962, probable vector of Leishmania mexicana ssp. in Viana municipality, Espírito Santo State, Brazil

Dos flebótomos atraídos pelo Proechimys iheringi numa área onde esse roedor foi achado naturalmente infectado por Leishmania mexicana ssp., 98,1% foram Lutzomyia gasparviannai, o que sugere que essa espécie não antropofílica seja o transmissor entre os roedores mas não habitualmente ao homem.

T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Infective stages of Leishmania in the sandfly vector and some observations on the mechanism of transmission

Infective stages of Leishmania (Leishmania) amazonensis, capable of producing amastigote infections in hamster skin, were shown to be present in the experimentally infected sandfly vector Lutzomyia flaviscutellata 15, 25, 40, 49, 70, 96 and 120 hours after the flies had received their infective blood-meal. Similarly, infective stages of Leishmania (L.) chagasi were demonstrated in the experimentally infected vector Lu. longipalpis examined 38, 50, 63, 87, 110, 135, 171 and 221 hours following the infective blood-meal, by the intraperitoneal inoculation of the flagellates into hamsters. The question of whether or not transmission by the bite of the sandfly is dependent on the presence of [quot ]metacyclic[quot ] promastigotes in the mouthparts of the vector is discussed.

Identification of vector species (Diptera: Simuliidae) of human onchocerciasis in the Amazonia focus of Brazil and Venezuela

The taxonomic status of three Amazonian simuliid species, Simulium guianese Wise, S. oyapockense Floch & Abonnenc and S. yarzabali Ramirez Perez is reviewed. Simulium cuasisanguineum Ramirez Perez, Yarzabal & Peterson is synonymized with S. oyapockense, and S. yarzabali is revalidated from its synonymy with S. incrustatum Lutz. The role of these three species in the transmission of human onchocerciasis and mansonelliasis in Amazonia is reviewed.

Vector salivation and parasite transmission

Saliva of blood-sucking arthropods contains substances that counteract the host's hemostatic and inflammatory reactions, allowing the arthropod to locate blood and keep it flowing during the blood meal. Parasites may manipulate this system in order to achieve increased transmission, both to vertebrate and to invertebrate hosts. Additionally, salivary pharmacological substances may locally immunosupress the delivery site, allowing initial colonization of the vertebrate host by the parasite.

Expression of Staphylococcus aureus clumping factor A in Lactococcus lactis subsp. cremoris using a new shuttle vector.

Staphylococcus aureus harbors redundant adhesins mediating tissue colonization and infection. To evaluate their intrinsic role outside of the staphylococcal background, a system was designed to express them in Lactococcus lactis subsp. cremoris 1363. This bacterium is devoid of virulence factors and has a known genetic background. A new Escherichia coli-L. lactis shuttle and expression vector was constructed for this purpose. First, the high-copy-number lactococcal plasmid pIL253 was equipped with the oriColE1 origin, generating pOri253 that could replicate in E. coli. Second, the lactococcal promoters P23 or P59 were inserted at one end of the pOri253 multicloning site. Gene expression was assessed by a luciferase reporter system. The plasmid carrying P23 (named pOri23) expressed luciferase constitutively at a level 10,000 times greater than did the P59-containing plasmid. Transcription was absent in E. coli. The staphylococcal clumping factor A (clfA) gene was cloned into pOri23 and used as a model system. Lactococci carrying pOri23-clfA produced an unaltered and functional 130-kDa ClfA protein attached to their cell walls. This was indicated both by the presence of the protein in Western blots of solubilized cell walls and by the ability of ClfA-positive lactococci to clump in the presence of plasma. ClfA-positive lactococci had clumping titers (titer of 4,112) similar to those of S. aureus Newman in soluble fibrinogen and bound equally well to solid-phase fibrinogen. These experiments provide a new way to study individual staphylococcal pathogenic factors and might complement both classical knockout mutagenesis and modern in vivo expression technology and signature tag mutagenesis.

Innovation sources and productivity in Catalonian firms: a quantile regression analysis

This paper explores the effects of two main sources of innovation -intramural and external R&D- on the productivity level in a sample of 3,267 Catalonian firms. The data set used is based on the official innovation survey of Catalonia which was a part of the Spanish sample of CIS4, covering the years 2002-2004. We compare empirical results by applying usual OLS and quantile regression techniques both in manufacturing and services industries. In quantile regression, results suggest different patterns at both innovation sources as we move across conditional quantiles. The elasticity of intramural R&D activities on productivity decreased when we move up the high productivity levels both in manufacturing and services sectors, while the effects of external R&D rise in high-technology industries but are more ambiguous in low-technology and knowledge-intensive services. JEL codes: O300, C100, O140. Keywords: Innovation sources, R&D, Productivity, Quantile regression

Why it is difficult to control Biomphalaria glabrata, the vector snail of schistosomiasis

The author studied some protective behaviors of Biomphalaria glabrata (vertical movements, response to molluscicides and response to water currents) and demonstrated how these activities hamper the control of this snail, which is the main vector of schistosomiasis in Brazil.

A priori ratemaking using bivariate poisson regression models

In automobile insurance, it is useful to achieve a priori ratemaking by resorting to gene- ralized linear models, and here the Poisson regression model constitutes the most widely accepted basis. However, insurance companies distinguish between claims with or without bodily injuries, or claims with full or partial liability of the insured driver. This paper exa- mines an a priori ratemaking procedure when including two di®erent types of claim. When assuming independence between claim types, the premium can be obtained by summing the premiums for each type of guarantee and is dependent on the rating factors chosen. If the independence assumption is relaxed, then it is unclear as to how the tari® system might be a®ected. In order to answer this question, bivariate Poisson regression models, suitable for paired count data exhibiting correlation, are introduced. It is shown that the usual independence assumption is unrealistic here. These models are applied to an automobile insurance claims database containing 80,994 contracts belonging to a Spanish insurance company. Finally, the consequences for pure and loaded premiums when the independence assumption is relaxed by using a bivariate Poisson regression model are analysed.

Morphological evidence by scanning electron microscopy of excretion of metacyclic forms of Trypanosoma cruzi in vector's urine

Comparision by scanning electron microscopy (SEM) of Trypanosoma cruzi flagellates attached to the cuticle of the rectal gland of infected Dipetalogaster maxima nymphs, showed marked differences before amd after feeding. Before feeding numerous metacyclic trypomastigotes were observed among the abundant epimastigotes that formed the carpet of flagellates. On the other hand, in insects that were allowed to urinate for 24 hours after a meal, the metacyclics were scarce,indicating that they had been detached by the urine flow. An asymetric type of cell division, probably originating both an epi-and a trypomastigote, was occasionally observed. The occurrence of swellings at different levels of the flagella of epimastigotes suggests that secondary sites of attachment may be common.