The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response

Encephalitis is a rare, but serious complication from vaccination against smallpox using replication competent strains of vaccinia virus. In this report we describe mutants of vaccinia virus, containing N-terminal deletions of the vaccinia virus interferon resistance gene, E3L, that are attenuated for neuropathogenesis in a mouse model system. These recombinant viruses replicated to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice but failed to spread to the lungs or brain. These viruses demonstrated reduced pathogenicity after intra-cranial infection as well, indicating a decrease in neurovirulence. Intra-nasal inoculation or inoculation by scarification with a low dose of recombinant virus containing a deletion of the entire N-terminal domain of E3L protected against challenge with a high dose of wild-type vaccinia virus, suggesting that this replication competent, but attenuated strain of vaccinia virus may have promise as an improved vaccine for protecting against smallpox, and as a vector for inducing mucosal immunity to heterologous pathogenic organisms.     

Pouteria campechiana leaf extract and its bioactive compound myricitrin are mosquitocidal against Aedes aegypti and Culex quinquefasciatus

Objective: To test the mosquitocidal potential of leaf extracts of Pouteria campechiana prepared with different solvents and elucidate the structure of an isolated mosquitocidal compound. Methods: The leaf extracts of Pouteria campechiana prepared with three solvents(petroleum benzene, ethyl acetate and acetone) and potential bioactive fractions were tested against various stages of Aedes aegypti and Culex quinquefasciatus by using the WHO protocols, and the chemical profile and its functional groups were identified by GC-MS and Fourier transmissioninfrared spectroscopy(FT-IR). The structure of bioactive compound was characterized by nuclear magnetic resonance(NMR) spectral technique. Results: The preliminary phytochemical results revealed the presence of alkaloids, amino acids, flavonoids, quinones, saponins, steroids, tannins, and terpenoids in the acetone extract. A significant toxic potential was observed in the acetone extract against both Aedes aegypti and Culex quinquefasciatus mosquitoes. The acetone extract exhibits remarkable larvicidal(LC_(50): 12.232 μg/mL and LC_(90): 63.970 μg/mL), pupicidal(LC_(50): 18.949 μg/mL and LC_(90): 167.669 μg/m L) and adulticidal(LC_(50): 20.689 μg/mL and LC_(90): 72.881 μg/mL) effects against Aedes aegypti. Furthermore, the same extract was subjected to isolation of bioactive compound by GCMS and FT-IR analysis. GC-MS results showed the presence of 5 major compounds, and octacosane(18.440%) was detected as the predominant compound. The FT-IR result of acetone extract demonstrated the presence of various functional groups like alkanes/alkynes, ester, aromatic and amides. The NMR spectrum results of isolated compound were well matched to glycoside linked flavonoids. Based on the chromatography and spectral techniques the isolate molecule was identified as myricitrin by FT-IR and nuclear magnetic resonance spectral data. Conclusion: The isolated compound myricitrin possesses a significant toxic effect in all stages of Aedes aegypti and Culex quinquefasciatus mosquito's with lowest LC_(50) and LC_(90) values.     

Multiple Metachronous Malignancies,One Patient with Three Primary Malignancies

Development of a primary cancer after treatment of the first with radiotherapy or chemotherapy is well documented, but it is common with hematological malignancies. Variety of reasons are suggested by various researchers, but a conclusive evidence is not yet available. Excepting a few correlations like the tamoxifen therapy and endometrial cancer, angiosarcoma of the breast following radiotherapy, occurrence of other metachronous malignancies seem to be dependent on genetic and environmental factors. A patient with three primary malignancies is presented here.     

Recurrent hyperhemolytic transfusion reaction in myelodysplastic syndrome- A case based approach

We present here a case report of a 27 year old female, with myelodysplatic syndrome suspected to have recurrent hyperhemolytic transfusion reactions (HHTR). Patient was transfusion dependent for ten years and was transfused with leukodepleted and irradiated Packed Red Blood Cells (PRBC). She presented with signs and symptoms of acute intravascular hemolysis, deranged coagulation profile with post transfusion Hb lower than baseline. Post transfusion workup was uneventful. She was managed conservatively with fluid support and methylprednisolone initially. After few uneventful transfusions, patient developed second episode of HHTR with compatible unit.Immunophenotype favored an inflammatory response possibly induced by monocytic lineage. As transfusion dependent, the patient required methylprednisolone as premedication and all subsequent transfusions were uneventful.