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641.
Battah S O'Neill S Edwards C Balaratnam S Dobbin P MacRobert AJ 《The international journal of biochemistry & cell biology》2006,38(8):1382-1392
Intracellular porphyrin generation following administration of 5-aminolaevulinic acid has been widely used in photodynamic therapy for a range of malignant and certain non-malignant lesions. However, cellular uptake of 5-aminolaevulinic acid is limited by its hydrophilic nature and improved means of delivery are therefore being sought. Highly branched polymeric drug carriers known as dendrimers are a promising new approach to drug delivery. The aim of this study was to investigate the efficacy of dendrimers conjugated with 5-aminolaevulinic acid for porphyrin production in the transformed PAM 212 keratinocyte cell line and skin explants. Each dendritic derivative incorporated three 5-aminolaevulinic acid residues which were conjugated as esters via methyl or propyl linkers to a central tertiary carbon whose remaining terminal bore an amino, aminobenzyloxycarbonyl or nitro group. In the cell line, all compounds were more efficient at low concentrations compared to equimolar 5-aminolaevulinic acid for porphyrin production, with the most efficient incorporating the longer propyl linker. This compound was also the most lipophilic according to partition coefficient measurements. The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure for all the compounds, together with minimal dark toxicity. Our findings indicate that the key factors influencing the efficacy of the dendritic derivatives are lipophilicity and steric hindrance within the dendritic structure which could restrict access to intracellular esterases for liberation of 5-aminolaevulinic acid. These findings should be taken into account in the design of larger dendrimers of 5-aminolaevulinic acid. 相似文献
642.
Iron is a metal highly concentrated in liver and brain tissue, and known to induce neuronal hyperactivity and oxidative stress.
It has been established that iron levels rise in the brain in some neurodegenerative diseases such as Parkinson's and Alzheimer's
diseases (AD). A body of evidence indicates a link between neuronal death and intracellular excessive calcium accumulation.
The aim of the present study was to investigate the effects of a calcium antagonist, flunarizine, on neurotoxicity induced
by intracerebroventricular (i.c.v.) iron injection. For this reason rats were divided into three groups as control, iron and
iron+flunarizine groups. Animals in iron and iron+flunarizine groups received i.c.v. FeCl3 injection (200 mM, 2.5 μl), while control rats received the same amount of saline into the cerebral ventricles. Rats in iron+flunarizine
group also received i.c.v. flunarizine (1 μM, 2 μl) following FeCl3 injection. All animals were kept alive for ten days following the operation and animals in iron+flunarizine group received
intraperitoneal (i.p.) flunarizine injections once a day (10 mg/kg/day) during this period. After ten days, rats were sacrificed.
The total numbers of neurons in hippocampus of all rats were estimated with the latest, unbiased stereological techniques.
Findings of the present study suggest that flunarizine may attenuate the neurotoxic effects of iron injection by inhibiting
the cellular influx of excessive calcium ions. 相似文献
643.
Nascent synaptic networks have a high incidence of silent synapses. In this issue of Neuron, Shen et al. show that a brief burst of action potentials rapidly awaken silent synapses by increasing the availability of synaptic vesicles for fusion through BDNF-triggered presynaptic actin remodeling mediated by the small GTPase Cdc42. 相似文献
644.
Cemalettin Alp Deniz Ekinci Mehmet Serdar Gültekin Murat Şentürk Ertan Şahin Ömer İrfan Küfrevioğlu 《Bioorganic & medicinal chemistry》2010,18(12):4468-4474
Here we propose a novel one-pot synthesis of new tosyl-pyrrole derivatives. By means of the new developed method, pyrrole derivatives were synthesized at room temperature in a single step, and a useful method is proposed for the synthesis of similar compounds. Moreover, inhibitions of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II by 1-tosyl-pyrrole and 1-tosyl-pyrrol-2-on derivatives were investigated. 1-Tosyl-pyrrole, 1-tosyl-1H-pyrrol-2(5H)-one, 5-hydroxy-1-tosyl-1H-pyrrol-2(5H)-one and 5-oxo-1-tosyl-2,5-dihydro-1H-pyrrol-2-yl acetate showed inhibitory action with Ki values in the range of 14.6–42.4 μM for hCA I and 0.53–37.5 μM for hCA II, respectively. All pyrrole derivatives were competitive inhibitors with 4-nitrophenylacetate as substrate. Some new synthesized pyrrole derivatives showed very effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors targeting other CA isoforms. 相似文献
645.
646.
Sebahat Cam Deniz Ertem Nerin Bahceciler Tunc Akkoc Isil Barlan Ender Pehlivanoglu 《Helicobacter》2009,14(1):1-8
Aim: To date, cross‐sectional and case–control studies suggest an inverse association between Helicobacter pylori infection and atopic diseases, whereas the immunologic basis has not been studied yet. In this study we investigated T helper (Th) cell function in H. pylori‐infected children and compared cytokine responses in atopic and non‐atopic groups. Methods: The study groups was recruited from a cohort of 327 healthy children evaluated and followed‐up for 6 years to assess the natural history of H. pylori infection. Seventy‐four of 136 healthy children who underwent 13C urea breath test were eligible and accepted to participate. All participants were evaluated by a questionnaire, and skin‐prick testing. According to the results, children were divided into four groups with respect to the presence or absence of H. pylori and atopy. Peripheral blood mononuclear cells isolated from 34 of 74 children were cultured with H. pylori, Der p 1, and phytohemagglutinin (PHA). Interferon‐gamma (IFN‐γ), interleukin (IL)‐4 and IL‐10, transforming growth factor‐beta (TGF‐β) levels were measured in supernatants. Results: The frequency of atopy was lower in H. pylori‐infected group (31.9% vs. 48.1, p = .22), while atopic symptoms were similar between infected and non‐infected children. While PHA and H. pylori induced IFN‐γ levels were significantly higher in H. pylori‐infected children, concomitant presence of both atopy and H. pylori decreased the level of PHA and H. pylori induced IFN‐γ production. PHA and Der p 1‐induced IL‐4 levels were higher in atopic children, and IL‐4 production was suppressed when they were concomitantly infected with H. pylori. The production of TGF‐β was found to be suppressed in atopic children irrespective of the presence of H. pylori infection. Conclusion: The results of the current study demonstrated a counteractive Th1 and Th2 cytokine interaction between H. pylori infection and atopy. However, this counteractive immunologic balance did not protect against atopy. 相似文献
647.
Semra Demokan Yusufhan Suoglu Mustafa Gözeler Deniz Demir Nejat Dalay 《Molecular biology reports》2010,37(7):3217-3226
Polymorphisms that alter the function of genes involved in the activation or detoxification of carcinogenic compounds can
influence an individuals risk of developing cancer. Polymorphic changes modulating the acetylation capacity of the N-acetyltransferase
(NAT) genes have been implicated in the risk of developing cancer. In this study the role of genetically determined individual
NAT1 and NAT2 genotypes, haplotypes and haplotype combinations in the predisposition to head and neck cancer was investigated. Polymorphic
regions of the NAT1 and NAT2 genes were analyzed in patients with head and neck cancer and healthy individuals by polymerase chain reaction-restriction
fragment length polymorphism. Distribution of the genotypes, allele frequencies, diplotypes and haplotypes and correlation
with clinical characteristics were evaluated. No association was observed between the NAT1*3, NAT1*10, NAT1*11, NAT2*5 and
NAT2*6 genotypes and risk of head and neck cancer. The NAT2*7 slow genotype was associated with reduced risk of disease. A significant association was observed between the fast acetylator
NAT2*4/NAT1*10 diplotype and risk of head and neck cancer. Combined haplotypes harboring the T1088A and C1095A variants characterizing the
NAT1*10 allele were associated with increased risk. Our results suggest that NAT1 and NAT2 gene combinations may influence the risk of developing head and neck cancer. 相似文献
648.
H. Sinan Suzen Emel Gucyener Ozgul Sakalli Zuhal Uckun Gulcin Kose Duygu Ustel Yalcin Duydu 《Molecular biology reports》2010,37(1):87-92
Oxidative stress is believed to play an important role in the pathogenesis of considerable number of complex diseases. The
antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) are important components of cell defense against oxidative
stress, and polymorphisms in the genes which regulate their expression may contribute to differences in susceptibility of
individuals to oxidative damage caused by reactive oxygen species. The aim of this study was to assess the distribution of
CAT C-262T and GPX1 Pro198Leu genotypic variants in a Turkish population. Genotyping analyses of CAT and GPX1 were conducted in 250 unrelated, healthy volunteers by the PCR-RFLP assay. The allele frequencies were 0.784 (C) and 0.216
(T) for CAT and 0.636 (C) and 0.364 (T) for GPX1 Pro198Leu. The genotype frequencies were 0.632 (CC), 0.304 (CT), and 0.064 (TT) for CAT and 0.416 (CC), 0.44 (CT), and 0.144 (TT) for GPX1 Pro198Leu. The genotype frequencies did not deviate from Hardy–Weinberg equilibrium. The results are compared with those
of other reported populations. They showed marked ethnic group differences. 相似文献
649.
Double Staining of Skeleton Using Microwave Irradiation 总被引:2,自引:0,他引:2
Celal Ilgaz Hatice Kocabiyik Deniz Erdo an Candan
zogul Tuncay Peker 《Biotechnic & histochemistry》1999,74(2):57-63
The fetal skeleton double staining method is used to reveal developmental abnormalities in the skeletal system. We used alizarin red S and al-cian blue successfully with microwave irradiation for skeletal double staining. The fixation time was reduced from 4-7 days to 2-2.5 min and the staining time was reduced from 4 days to 23 min. 相似文献
650.
Stephanie Fischinger Deniz Cizmeci Davy Deng Shannon P. Grant Nicole Frahm Julie McElrath Jonathan Fuchs Pierre-Alexandre Bart Giuseppe Pantaleo Michael Keefer William O. Hahn Nadine Rouphael Gavin Churchyard Zoe Moodie Yeycy Donastorg Hendrik Streeck Galit Alter 《PLoS pathogens》2021,17(11)
Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies.Trial registration: ClinicalTrials.gov , NCT00801697, NCT00961883, NCT02207920, NCT00125970). NCT02852005相似文献