Fused and spiro nitrogen heterocycles of quinuclidine and its C-nucleosides

Quinuclidin-3-one (1) was used as a versatile intermediate for the synthesis of fused and spiro quinuclidine and its C-nucleosides. The reaction of 1 with formalin and secondary amines namely; morpholine, piperidine, and piperazine afforded the corresponding Mannich bases 2-4 in acid medium. Quinuclidino[3,2-b]pyran 5 has been synthesized via a selective cyclocondensation reaction between Mannich base of quinuclidinone hydrochloride 2 and malononitrile. The transformation of 1 with formalin and methylamine in molar ratio (1:20:2) afforded the spiro compound 7. Ring expansion of 2 under Schmidt reaction conditions gave the 1,3-diazabicyclo[3.2.2]nonanone derivative 6. Eventually, the synthesis of C-nucleosides 10, 12-14 were achieved by using aldohexoses and aldopentose catalyzed by zinc chloride, while, the bis-quinuclidine derivative 15 was obtained by using sodium carbonate. Newly synthesized compounds were characterized by IR, 1H NMR, and mass spectral data

RANKL EXPRESSION AND METABOLIC CHANGES IN OVARIECTOMIZED RATS AND THE POSSIBLE PROTECTION BY VEGETABLE FORMULA.

 Objective: This study was to evaluate complications of osteoporosis in ovariectomized rats and the possibility to ameliorate these changes by consumption of vegetable formula. Furthermore, transcription of mRNA of RANKL gene was matched with bone mass density (BMD) and bone formation marker (human procollagen 1 N terminal peptide [PINP]).Methods: Thirty rats were divided into three groups. The first is non ovariectomized control group (NOVXC), the second is ovariectomized control group (OVXC), and the third is ovariectomized rats supplemented with the vegetable formula (OVXT). Animals were fed for 8 successive weeks. Animals were treated and sacrificed under the recommended ethics of laboratory animal's treatment. The vegetable mixture was formulated with the purpose to correct the bone compromise and supply all the presumed deficient elements and hormone.Results: Chemical analysis showed that the formulated vegetable mixture had a high amount of flavonoids as catechin (100 mg/100 g of dry weight) and polyphenols as tannic acid (1000 mg/100 g dry weight. Furthermore, it had high reducing power (1,1-diphenyl-2-picrylhydrazyl radical showed inhibition percentage of 91.81%.). Several phytochemicals necessary for bone health were demonstrated in the vegetable mixture using high-performance liquid chromatography. RANKL/GAPDH mRNA transcription ratio showed marked an increase in OVXC versus the control NOVXC rats (1.00 vs. 0.199, respectively) accompanied with a drop in BMD (0.157 vs. 0.25 mg/cm2, respectively) and PINP values (27.9±2.8 compared to NOVXC 34±2.4 μ/L, respectively). The vegetable mixture supplementation showed better values of BMD and PINP in OVXT group directed back toward normal (0.183 mg/cm2 and 29.35±3.4 μ/L, respectively). Furthermore, analysis of blood plasma of supplemented group showed lower blood glucose, lipid profile, and oxidative markers if compared to that in OVXC group.Conclusion: It may be concluded that the plant formula was effective to minimize health hazards in ovariectomized rats and maybe for postmenopause women. Perhaps longer time may be needed for more significant and clear effect

Expression plasticity of Phlebotomus papatasi salivary gland genes in distinct ecotopes through the sand fly season

<p>Abstract</p> <p>Background</p> <p>Sand fly saliva can drive the outcome of <it>Leishmania </it>infection in animal models, and salivary components have been postulated as vaccine candidates against leishmaniasis. In the sand fly <it>Phlebotomus papatasi</it>, natural sugar-sources modulate the activity of proteins involved in meal digestion, and possibly influence vectorial capacity. However, only a handful of studies have assessed the variability of salivary components in sand flies, focusing on the effects of environmental factors in natural habitats. In order to better understand such interactions, we compared the expression profiles of nine <it>P. papatasi </it>salivary gland genes of specimens inhabiting different ecological habitats in Egypt and Jordan and throughout the sand fly season in each habitat.</p> <p>Results</p> <p>The majority of investigated genes were up-regulated in specimens from Swaymeh late in the season, when the availability of sugar sources is reduced due to water deprivation. On the other hand, these genes were not up-regulated in specimens collected from Aswan, an irrigated area less susceptible to drought effects.</p> <p>Conclusion</p> <p>Expression plasticity of genes involved with vectorial capacity in disease vectors may play an important epidemiological role in the establishment of diseases in natural habitats.</p

Profiling of human acquired immunity against the salivary proteins of Phlebotomus papatasi reveals clusters of differential immunoreactivity

Citation: Geraci, Nicholas S., Rami M. Mukbel, Michael T. Kemp, Mariha N. Wadsworth, Emil Lesho, Gwen M. Stayback, Matthew M. Champion, et al. 2014. “Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus Papatasi Reveals Clusters of Differential Immunoreactivity.” The American Journal of Tropical Medicine and Hygiene 90 (5): 923–38. https://doi.org/10.4269/ajtmh.13-0130.Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents

Phlebotomus papatasi SP15: mRNA expression variability and amino acid sequence polymorphisms of field populations

Citation: Ramalho-Ortigao, M., Coutinho-Abreu, I. V., Balbino, V. Q., Figueiredo, C. A. S., Mukbel, R., Dayem, H., . . . McDowell, M. A. (2015). Phlebotomus papatasi SP15: mRNA expression variability and amino acid sequence polymorphisms of field populations. Parasites & Vectors, 8, 14. doi:10.1186/s13071-015-0914-2Background: The Phlebotomus papatasi salivary protein PpSP15 was shown to protect mice against Leishmania major, suggesting that incorporation of salivary molecules in multi-component vaccines may be a viable strategy for anti-Leishmania vaccines. Methods: Here, we investigated PpSP15 predicted amino acid sequence variability and mRNA profile of P. papatasi field populations from the Middle East. In addition, predicted MHC class II T-cell epitopes were obtained and compared to areas of amino acid sequence variability within the secreted protein. Results: The analysis of PpSP15 expression from field populations revealed significant intra-and interpopulation variation.. In spite of the variability detected for P. papatasi populations, common epitopes for MHC class II binding are still present and may potentially be used to boost the response against Le. major infections. Conclusions: Conserved epitopes of PpSP15 could potentially be used in the development of a salivary gland antigen-based vaccine.Additional Authors: Lobo, N. F.;Mahon, A. R.;Emrich, S. J.;Kamhawi, S.;Collins, F. H.;McDowell, M. A

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p