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Mycobacterium tuberculosis , Tuberculosis , Femenino , Embarazo , Humanos , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
Cryptococcus neoformans, an encapsulated fungal pathogen is evolving as a major threat to immune-compromised patients and rarely to healthy individuals also. The cell wall bound capsular polysaccharide, melanin pigment and biofilm formation are major virulence factors that are known to contribute to cryptococcal meningitis. In the present study, a furanone derivative, (E)-5-benzylidenedihydrofuran-2(3H)-one (compound-6) was evaluated against biofilm of seven different strains of C. neoformans in melanized and non-melanized condition. In addition, the efficacy of compound-6 in activation of TLR-2, opsonophagocytosis, and modulation of cytokine expression during phagocytosis were studied. During the biofilm study, we found that moderate capsule size favored biofilm formation. Interestingly, the minimum biofilm eradication concentration (MBEC0.5) of melanized biofilm was found to be achieved at 1- to 1.7-fold higher MBEC0.5 of non-melanized cells. The maximum eradication of 77% and 69% of non-melanized and melanized biofilm were observed. The capsule size was reduced to half of its size with marked changes in morphology. Furthermore, expression of TLR2, iNOS and pro-inflammatory cytokines such as TNF-α, IL-12, and IFN-γ were also facilitated by compound-6. The correlation analysis showed a positive correlation between phagocytosis and the expression of TLR-2, iNOS, IL-6, IL-12. Collectively, the significant effect of compound-6, anti-melanization activity, antibiofilmand effective immunomodulant could be an interesting dual strategy drug agonist against cryptococcal meningitis.
Asunto(s)
Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Cryptococcus/efectos de los fármacos , Proteínas Opsoninas/fisiología , Fagocitosis/efectos de los fármacos , Animales , Antifúngicos/síntesis química , Antifúngicos/química , Cápsulas Bacterianas/efectos de los fármacos , Cápsulas Bacterianas/fisiología , Células Cultivadas , Criptococosis/inmunología , Criptococosis/microbiología , Cryptococcus/fisiología , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/fisiología , Furanos/síntesis química , Furanos/química , Furanos/farmacología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Melaninas/metabolismo , Meningitis Criptocócica/inmunología , Meningitis Criptocócica/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , Proteínas Opsoninas/metabolismoRESUMEN
PURPOSE: To quantify the benefit of adaptive fractionation, through both theoretical test cases and patient data. METHODS: We consider the effect of delivering a different fraction size based on the changes observed in the patient anatomy. Given that a fixed prescription dose must be delivered to the tumor over the course of the treatment, we find that adaptively varying the fraction size results in a lower cumulative dose to a primary organ-at-risk (OAR). We construct a one dimensional theoretical example by randomly varying the distance between the tumor and OAR, and simulate the benefit of adaptive fractionation in such a setting. Next, we test our methodology using contoured daily CT images from 5 prostate patients. RESULTS: For the theoretical example, we found about a 10% decrease in dose to the OAR when using a uniformly distributed motion model and a 20% daily fraction size deviation. In general, the amount of decrease in dose to the OAR varied significantly (5-85%) for these theoretical test cases depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. Preliminary results from the prostate patients indicate an average reduction in dose to the rectum of 1.4%, 3.5%, and 7.0% when using 20%, 50%, and 100% daily fraction size deviations, respectively. CONCLUSIONS: Qualitatively, the theoretical example indicates that adaptive fractionation is beneficial for disease sites in which there is significant inter-fractional motion. We also expect greater benefit when using many fractions and allowing for large daily fraction size deviations. For the prostate disease site in particular, we find that adaptive fractionation is beneficial only when allowing large daily fraction size deviations. Further research quantifying the gain for disease sites that exhibit significant inter-fractional motion, such as rectal and cervical cancers, would be useful. Partially supported by Siemens.
RESUMEN
SUMMARY: A simian hepatitis A virus (HAV) was identified retrospectively in a faecal sample from a rhesus monkey in India, inoculated in 1995 with a faecal suspension from a suspected patient of non-A to E hepatitis. The monkey was in captivity for 2 years in one of the experimental primate facilities in western India before being moved to the National Institute of Virology, Pune for experimentation. Phylogenetic analysis based on a partial sequence of the 5' noncoding region placed this virus in genotype V, the only other member being the AGM-27 strain recovered in 1986 from African green monkeys in Kenya. The source of infection of the monkey remains unclear. The full genome was amplified in nine fragments and sequenced. The genome of the Indian simian HAV (IND-SHAV) is 7425 nucleotides long including the poly-A tail of 14 nucleotides at the 3' end. At the nucleotide and amino acid levels, IND-SHAV was 99.8 and 100% identical with AGM27, respectively.
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Animales de Laboratorio/virología , Animales Salvajes/virología , Chlorocebus aethiops/virología , Virus de la Hepatitis A/clasificación , Hepatitis A/veterinaria , Macaca mulatta/virología , Enfermedades de los Monos/virología , Animales , Cartilla de ADN , Genoma Viral , Hepatitis A/virología , Virus de la Hepatitis A/genética , Virus de la Hepatitis A/aislamiento & purificación , India , Kenia , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ADNRESUMEN
A DNA molecular hybridization technique employing Duck Hepatitis B Virus (DHBV) DNA of 3.0 kilobase pairs as a probe was used to screen for the presence of DHBV DNA in blood samples, collected from 90 apparently healthy Indian country ducks. Six out of 90 ducks showed positivity for DHBV DNA in serum (5.4%) and only 4 out of 6 DHBV DNA positive ducks answered in Counter Immuno Electrophoresis (CIEP) using specific antibody against DHBV surface antigen raised in Guinea pig. The results indicate the pilot observation that (a) DHBV carrier status exists to a tune of 5.4% among apparently healthy Indian country ducks also and (b) DHBV probe can be employed as a sensitive and reliable assay for DHBV DNA detection in DHBV infected ducks.