North Chicago, IL, United States
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Alam M.Z.,Hokkaido University | Alam M.Z.,Bangladesh Agricultural University | Nakao R.,Hokkaido University | Sakurai T.,Hokkaido University | And 6 more authors.
Infection, Genetics and Evolution | Year: 2014

The Leishmania strains from different epidemic areas in China were assessed for their genetic relationship. Twenty-nine strains of Leishmania infantum isolated from 1950 to 2001 were subjected to multilocus microsatellite typing (MLMT) using 14 highly polymorphic microsatellite markers. Twenty-two MLMT profiles were recognized among the 29 L. infantum strains, which differed from one another in 13 loci. Bayesian model-based and distance-based analysis of the data inferred two main populations in China. Sixteen strains belonged to one population, which also comprised previously characterized strains of L. infantum non-MON1 and Leishmania donovani. The parasites within this population are assignable to a distinct cluster that is clearly separable from the populations of L. donovani elsewhere, i.e. India, Sri Lanka and East Africa, and L. infantum non-MON1 from Europe. The remaining 13 Chinese strains grouped together with strains of L. infantum MON1 into another population, but formed a separate cluster which genetically differs from the populations of L. infantum MON1 from Europe, the Middle East, Central Asia and North Africa. The existence of distinct groups of L. infantum MON1 and non-MON1/. L. donovani suggests that the extant parasites in China may have been restricted there, but not recently introduced from elsewhere. © 2014 Elsevier B.V.


Panchal H.B.,East Tennessee State University | Shah T.,Chicago Medical School RFUMS | Patel P.,Holston Valley Medical Center | Albalbissi K.,East Tennessee State University | And 4 more authors.
Journal of Cardiovascular Pharmacology and Therapeutics | Year: 2013

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 μmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <.05 was considered as a level of significance. Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 μmol/L (MD: -14.4, CI: -21.6 to -7.2, P < .001) and 20 mmol/L (MD: -14.9, CI: -22.9 to -6.8, P < .001), significantly lower PRUs (MD: -45, CI: -59.4 to -30.6, P < .001) and PRI (MD: -26, CI: -36.8 to -15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy. © 2013 The Author(s).


Dutta S.,Chicago Medical School RFUMS | Waki K.,Chicago Medical School RFUMS | Chang K.P.,Chicago Medical School RFUMS
Photochemistry and Photobiology | Year: 2012

Leishmania were previously shown to undergo photolysis when their transgenic mutants were induced endogenously to accumulate cytoplasmic uroporphyrin or when loaded exogenously with aluminum phthalocyanine chloride. A combinational use of both is reported here, which renders Leishmania far more susceptible to photolysis. Fluorescence microscopy of cells loaded with the two photosensitizers localized them to different subcellular sites. Pre-exposure of Leishmania to both synergistically sensitized them for photolysis as extracellular promastigotes and intracellular amastigotes in infected macrophages in vitro when illuminated at specific wavelengths to excite the respective photosensitizers for production of reactive oxygen species. Both Leishmania stages lost their viability completely when doubly photosensitized optimally and illuminated at low intensity, the host cells being left unscathed. Inoculation of mice with photoinactivated Leishmania produced no lesions, which invariably developed in the control groups during a period of observations for 8 weeks. Pretreatment of Leishmania with both photosensitizers rendered these cells susceptible to clearance from the ear dermis by white light illumination. The results suggest that double photosensitization for synergistic activity enhances the efficacy and safety of photodynamic therapy in general and for Leishmania in particular. Leishmania parasitize the phagolysosomes of antigen-presenting cells and are thus uniquely suitable for targeted delivery of vaccines. When preloaded exogenously with photosensitizers, e.g. aluminum phthalocyanine chloride (AlPhCl; A) or when exposed to aminolevulinate as transgenic mutants to accumulate uroporphyrin endogenously (B), Leishmania are photolyzed in these cells selectively, but incompletely. Double photosensitization of Leishmania with both (C) increases their photolysis significantly so that no survivors are detectable in both in vitro and in vivo systems. The potential utility of Leishmania as a photodynamic vaccine carrier is thus enhanced by the double photosensitization to provide a favorable profile of their safety. © 2012 The American Society of Photobiology.


PubMed | Chicago Medical School RFUMS
Type: Journal Article | Journal: Photochemistry and photobiology | Year: 2012

Leishmania were previously shown to undergo photolysis when their transgenic mutants were induced endogenously to accumulate cytoplasmic uroporphyrin or when loaded exogenously with aluminum phthalocyanine chloride. A combinational use of both is reported here, which renders Leishmania far more susceptible to photolysis. Fluorescence microscopy of cells loaded with the two photosensitizers localized them to different subcellular sites. Pre-exposure of Leishmania to both synergistically sensitized them for photolysis as extracellular promastigotes and intracellular amastigotes in infected macrophages in vitro when illuminated at specific wavelengths to excite the respective photosensitizers for production of reactive oxygen species. Both Leishmania stages lost their viability completely when doubly photosensitized optimally and illuminated at low intensity, the host cells being left unscathed. Inoculation of mice with photoinactivated Leishmania produced no lesions, which invariably developed in the control groups during a period of observations for 8 weeks. Pretreatment of Leishmania with both photosensitizers rendered these cells susceptible to clearance from the ear dermis by white light illumination. The results suggest that double photosensitization for synergistic activity enhances the efficacy and safety of photodynamic therapy in general and for Leishmania in particular.

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