Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria. 相似文献
Vascular dementia (VaD) is a degenerative cerebrovascular disorder that leads to progressive decline in cognitive abilities and memory. Several reports demonstrated that oxidative stress and endothelial dysfunction are principal pathogenic factors in VaD. The present study was constructed to determine the possible neuroprotective effects of simvastatin in comparison with cilostazol in VaD induced by l-methionine in rats. Male Wistar rats were divided into four groups. Group I (control group), group II received l-methionine (1.7 g/kg, p.o.) for 32 days. The remaining two groups received simvastatin (50 mg/kg, p.o.) and cilostazol (100 mg/kg, p.o.), respectively, for 32 days after induction of VaD by l-methionine. Subsequently, rats were tested for cognitive performance using Morris water maze test then sacrificed for biochemical and histopathological assays. l-methionine induced VaD reflected by alterations in rats’ behavior as well as the estimated neurotransmitters, acetylcholinesterase activity as well as increased brain oxidative stress and inflammation parallel to histopathological changes in brain tissue. Treatment of rats with simvastatin ameliorated l-methionine-induced behavioral, neurochemical, and histological changes in a manner comparable to cilostazol. Simvastatin may be regarded as a potential therapeutic strategy for the treatment of VaD. To the best of our knowledge, this is the first study to reveal the neuroprotective effects of simvastatin or cilostazol in l-methionine-induced VaD.
Context: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption.
Objective: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption.
Method: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol? or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs.
Results and discussion: DFV-loaded NLC formulations possessed average particle size ranging from 160.40?nm to 743.7?nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12?h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation.
Conclusion: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV. 相似文献
Acanthamoebae polyphaga Mimivirus (APM) is the largest known dsDNA virus. The viral particle has a nearly icosahedral structure with an internal capsid shell
surrounded with a dense layer of fibrils. A Capsid protein sequence, D13L, was deduced from the APM L425 coding gene and was
shown to be the most abundant protein found within the viral particle. However this protein remained poorly characterised
until now. A revised protein sequence deposited in a database suggested an additional N-terminal stretch of 142 amino acids
missing from the original deduced sequence. This result led us to investigate the L425 gene structure and the biochemical
properties of the complete APM major Capsid protein. 相似文献
The aim of this study was to confirm if there is a link between the alteration in blood levels of trace elements (chromium,
copper, lead, cadmium, and zinc) and dehydroepiandrosterone sulfate (DHEAS) in healthy and diabetic states. This study is
the first study to test these parameters in Egyptians. The study included 150 subjects divided into the following four groups:
healthy middle-aged, healthy elderly, middle-aged diabetics, and elderly diabetics. Our results revealed a statistically significant
decrease in the level of DHEAS in the elderly compared to middle-aged healthy and diabetic groups (p < 0.05). There was a significant difference between the middle-aged groups with respect to zinc, copper, chromium, and cadmium
levels. Zinc and copper were lower in the diabetic subjects while chromium and cadmium were higher in the same group in comparison
to healthy subjects. In the elderly groups, there were significant increases in chromium and cadmium levels in diabetic subjects
rather than healthy ones. There was a significant increase in the thiobarbituric acid reactive substance level in the elderly
healthy and diabetic groups and a significant decrease in the glutathione level in the elderly groups. There was no correlation
between the levels of trace elements and DHEAS or between the levels of DHEAS, oxidants, and antioxidants in all of the tested
groups. In conclusion, only the DHEAS level was correlated with age. There was no difference between the diabetic and healthy
groups with respect to the levels of trace elements, with the exception of chromium and cadmium, which suggests the effect
of pollution on the pathogenesis of diabetes in Egyptians. No correlation existed between the levels of DHEAS and trace elements,
oxidants, and antioxidants. Finally, we believe that there is a large regional variation in the levels of trace elements due
to different environmental exposure and nutritional factors which are responsible for contradictory results regarding the
pathogenesis of diseases related to alterations in the levels of trace elements. 相似文献
The purpose of the present study was to investigate the osteoprotective effects of soybean oil (SbO) and sesame oil (SO) in ovarictomized (OVX) rats. The results indicated that the OVX rats exhibited a significant decrease in Ca and P level in both serum and bone, the activities of the antioxidant enzymes SOD and CAT and the antioxidant biomarker GSH accompanied with a marked increase in the oxidative stress markers MDA and PC, the inflammatory indices (TNF-α, CRP levels, WBCs counts and ACP activity) in, both, bone and serum. Supplementating the diet of the OVX rats with SbO (15 % w/w) or SO (10 % w/w) for 2 months to resulted in modulation of the alterations in all tested parameters and succeeded to restore minerals, antioxidant enzymes, antioxidant biomarkers, oxidative stress markers, inflammatory indices, and WBCs counts. It could be concluded that the consumption of diets supplemented with SbO or SO might be useful for preventing bone loss caused by estrogen deficiency in ovariectomy status. 相似文献