Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development. 相似文献
We sought to assess the magnitude of functional decline and the natural history of the operated kidney residual function after zero-ischemia nephron-sparing surgery (Z-NSS) in children with unilateral renal tumor (URT).
Patients and methods
50 children were treated for URT at our surgical unit between 1992 and 2016. Of these 12 who underwent Z-NSS were available for the current analysis. Operated kidney function was assessed by 99mTc-dimercapto-succinic acid (DMSA) renal scintigraphy. Operated kidney volume was assessed by renal ultrasonography.
Results
A positive correlation between split renal function and split renal volume was found (P?=?0.001). The subset of patients with ≥ 40% preservation of operated kidney function/volume (OKF/V) had no-time dependent changes during adolescence. The subset of patients with < 40% OKF/V preservation had a catch-up growth that after puberty reached values not much different from those with ≥ 40% OKF/V preservation. At 5?years of follow-up, 3 of 5 patients with baseline dysfunction (eGFR between 40.8 and 89.4?ml/min/1.73?m2) presented with a global renal function within normal range. After puberty, all patients presented with global renal function within normal values (eGFR between 95 and 151?ml/min/1.73 m2).
Conclusions
In children with URT who underwent Z-NSS, the pattern of OKF/V recovery suggests that compensatory catch-up growth capacity during childhood minimizes OKF/V decline more than Z-NSS.
Level of evidence
Level I prognosis study — prospective cohort study with > 80% follow-up and all patients enrolled at same time point in disease. 相似文献
Testing for high-risk human papilloma virus (HR-HPV) is an effective approach to the prevention of cervical cancer. This study in the Atsinanana area of Madagascar aimed to compare the management of women screened by visual inspection after coloration with acetic acid (VIA) and the management of women screened by HPV with VIA as a triage test.
Method
During the last two screening campaigns, the first patients (between 28 and 120 women par center) were sampled using a dry swab, just before the acetic acid application, to test 14 genotypes of HR-HPV using Roche Diagnostics Cobas® Test. We compared current management practices based on primary VIA to those that would have been implemented if the clinician had followed the recommendations of the World Health Organization for HPV-based primary screening. We used a regression Poisson model with random effect and robust variance.
Results
Among the 250 screened-women, 28 (11.2%) had acidophilic lesions of the uterine cervix or suspected lesions of invasive cancer (IVA +). The HPV test was positive in 62 cases (24.8%). The HPV-based screening strategy would have reduced by 52% the number of women needing thermo-coagulation treatment: 24 women (9.6%) with primary VIA-based screening vs. 13 women (5.2%) with primary HPV-based screening; RR: 0.52 and 95%CI: 0.27–1.02. The diagnosis of severe dysplastic lesion or invasive cancer would not have changed.
Conclusion
Primary HPV-based screening is a strategy that could be useful for low-resource countries like Madagascar. It would reduce the rate of false positives and unnecessary treatments compared to the current strategy based on primary IVA. The questions of the feasibility and cost-benefit of this strategy should be further explored. 相似文献
Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.
Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.
Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk. 相似文献
Asensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-C18 column (3.5 μm, 2.1 mm×100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detectionwas performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3→352.9 for isochlorogenic acid B and m/z 227.1→143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5–2500 ng/mL (r2 = 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg. 相似文献
In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders. 相似文献