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Transfection activity of antisense oligodeoxynucleotides (ODN)-loaded cationic liposomes is mainly restricted by uptake and ODN release into cytoplasm, which is difficult to evaluate in cell culture studies. Well-designed models of cellular membranes, aim of the present study, might facilitate investigation of such processes. In this investigation, a phosphorothioate ODN was actively encapsulated in a DODAP-containing cationic liposome by ethanol injection with 73% efficiency. ODN release was determined by fluorescence dequenching of FITC-ODN upon incubation of liposomes with early endosomal (EE), late endosomal (LE) and plasma membranes (PM) models. LE provided the highest release (up to 76%) in a temperature-dependent manner. Release by EE (<16%), total PM (<11%) and PM external layer ( approximately 0) were not temperature sensitive. These differences are attributed to lipid charge, chain mobility, critical packing parameter and cholesterol content of the models. Intracellular distribution of FITC-ODN, determined by fluorescence microscopy and flowcytometry in the presence and absence of sodium azide, confirmed that liposomes were internalized mainly via endocytosis; hence inability of our PL models to simulate such active processes. Instead, release of ODN from endosomes into cytoplasm was pH-sensitive and in good agreement with model membrane studies in terms of amount and mechanism. 相似文献
105.
Verma SK Ahmad S Shirazi N Barthwal SP Khurana D Chugh M Gambhir HS 《Human & experimental toxicology》2007,26(12):979-981
There have been no case reports on aluminum phosphide-induced pancreatitis in the literature available. In this report, we present the case of a young man who developed acute pancreatitis and probably acute myocarditis following ingestion of aluminum phosphide pellets in the absence of the usual risk factors and after exclusion of other possible causes of pancreatitis. In the absence of re-challenge, we put forth the probable causative association of pancreatitis with aluminum phosphide or phosphine gas, its active pesticidal component. 相似文献
106.
L Gabriele F Moretti MA Pierotti FM Marincola R Foà FM Belardelli 《Journal of translational medicine》2006,4(1):1-5
Purpose
Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM?) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM.Methods
In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l08 pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 109 pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9 – 1424).Results
There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients.Conclusion
This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer. 相似文献107.
Background:
The maintenance of balance is an essential requirement for the performance of daily tasks and sporting activities and muscular fatigue is a factor to impair postural control, so this study was done to compare the effect of selected muscle groups fatigue on postural control during bipedal stance in healthy subjects.Materials and Methods:
Fifteen healthy female students (24.3 ± 2.6 years) completed three testing session with a break period of at least 2 days. During each session, postural control was assessed during two 30-s trials of bipedal stance with eyes close before and after the fatigue protocol. Fatigue protocols were performed by 60% of their unfatigued Maximum Voluntary Contraction of unilateral ankle plantar flexors, bilateral lumbar extensors and bilateral neck extensors. One of the three fatigue protocols was performed on each session.Results:
The result showed that fatigue had a significant effect on COP velocity and it increase COP velocity but there was not found any difference in postural sway between muscle groups.Conclusion:
Localized muscle fatigue caused deficits in postural control regardless of the location of fatigue. Authors suggest the possibility of the contributions of central mechanisms to postural deficits due to fatigue and it seems that difference was not between muscle groups due to central fatigue. 相似文献108.
Jasmine Shirazi Sonia Shah Divya Sagar Michael R. Nonnemacher Brian Wigdahl Zafar K. Khan Pooja Jain 《Journal of neuroimmune pharmacology》2013,8(5):1181-1196
Drug abuse alone has been shown to cause epigenetic changes in brain tissue that have been shown to play roles in addictive behaviors. In conjunction with HIV-1 infection, it can cause epigenetic changes at the viral promoter that can result in altered gene expression, and exacerbate disease progression overall. This review entails an in-depth look at research conducted on the epigenetic effects of three of the most widely abused drugs (cannabinoids, opioids, and cocaine), with a particular focus on the mechanisms through which these drugs interact with HIV-1 infection at the viral promoter. Here we discuss the impact of this interplay on disease progression from the point of view of the nature of gene regulation at the level of chromatin accessibility, chromatin remodeling, and nucleosome repositioning. Given the importance of chromatin remodeling and DNA methylation in controlling the retroviral promoter, and the high susceptibility of the drug abusing population of individuals to HIV infection, it would be beneficial to understand the way in which the host genome is modified and regulated by drugs of abuse. 相似文献
109.
Objectives
To analyze the concept of “case series” in the medical literature compared with case reports.Methods
A PubMed search for articles published during 2009 which had “case series” in their title was performed. A total number of 621 articles were retrieved. 586 papers were included in the analysis and 35 were excluded (18 were commentary letters, 5 were not in English, and twelve could not be retrieved by our Library). The number of patients and category of these articles were analyzed.Results
The median (range) of the number of cases of articles having “case series” in their title was 7 (1–6432) cases. 186/ 586 articles had less than 5 cases (31.7%, 95% CI (28.3–35.1%)). The median (range) of the number of cases of articles having “case report” as their publication type was 4 (1–178) cases. Out of the 219 articles categorized as case reports 114 (52.1%, 95% CI (45.6–58.6%)) had less than five cases.Conclusions
The concept of “case series” is not well defined in the literature and does not reflect a specific research design. We suggest that a case series should have more than four patients while four paitents or less should be reported individually as case reports. 相似文献110.
Saidi P Sadeghi M Shirazi A Tenreiro C 《Australasian physical & engineering sciences in medicine / supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine》2011,34(2):223-231
Brachytherapy dose distributions are calculated for 15 mm ROPES eye plaque loaded with model Theragenics200 and IR06-103Pd seeds. The effects of stainless steel backing and Acrylic insert on dose distribution along the central axis of the eye
plaque and at critical ocular structure are investigated. Monte Carlo simulation was carried out with the Version 5 of the
MCNP. The dose at critical ocular structure by considering the eye composition was calculated. Results are compared with the
calculated data for COMS eye plaque loaded with Theragenics200 palladium-103 seeds and model 6711 iodine-125 seed. The air
kerma strength of the IR06-103Pd seed to deliver 85 Gy in apex of tumor in water medium was calculated to be 4.10 U/seed. Along the central axis of stainless
steel plaque loaded with new 103Pd seeds in Acrylic insert, the dose reduction relative to water is 6.9% at 5 mm (apex). Removal of the Acrylic insert from
the plaque (replacing with water) did not make significantly difference in dose reduction results (~0.2%). The presence of
the stainless steel backing results in dose enhancement near the plaque relative to water. Doses at points of interest are
higher for ROPES eye plaque when compared to COMS eye plaque. The dosimetric parameters calculated in this work for the new
palladium seed, showed that in dosimetry point of view, the IR06-103Pd seed is suitable for use in brachytherapy. The effect of Acrylic insert on dose distribution is negligible and the main
effect on dose reduction is due to the presence of stainless steel plaque backing. 相似文献