scholarly journals Surface Adsorption of the Alpha-Emitter Astatine-211 to Gold Nanoparticles Is Stable In Vivo and Potentially Useful in Radionuclide Therapy

2021 ◽  
Vol 2 (4) ◽  
pp. 196-207
Author(s):  
Emanuel Sporer ◽  
Christian B. M. Poulie ◽  
Sture Lindegren ◽  
Emma Aneheim ◽  
Holger Jensen ◽  
...  

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sean Swetledge ◽  
Renee Carter ◽  
Rhett Stout ◽  
Carlos E. Astete ◽  
Jangwook P. Jung ◽  
...  

AbstractPolymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye.


Author(s):  
Said Yousef Swilem

The purpose of this study is to examine the efficiency of a group counseling program based on psychodrama in improving self-awareness and reducing tension among tenth grade students in Qalqilia City and examining the nature and the direction of the relationship between self-consciousness and tension, the sample of study consisted of (20) students whom were distributed randomly equally to two groups the first is an experimental contains (10) students and the second is a control group contains (10) students in light of a tension variable, they are drawn out from (152) students in governmental schools who obtained the highest stress scale for the current study, a counseling program has been built based on the principles and methodology methods of psychodrama which contained (13) sessions, the current study used a measure of self-awareness and tension before and after the program. The researcher used the semi-experimental design to verify the validity of the two instruments they were presented to a group of specialized consultants. The stability coefficient was then calculated using Cronbach Alpha, where the stability value of the self-awareness scale was 0.81 and tension scale was 0.90. The mean and standard deviations were calculated and the Shapiro-Wilk test was used to examine the normal distribution probability of the variables of self-awareness and tension. The results revealed in the non-moderate distribution of individual responses to the two variables. The Mann-Whitney test, the Wilcoxon Signed Ranks Test, and the Spearman Product-Moment Correlation Coefficient test were used. The results showed differences between the experimental and control groups in the post-test of self-awareness and stress measures and for group members this is an indication of the effectiveness of the psychodrama -based counseling program in improving self-awareness and reducing stress among tenth grade students in Qalqilia city and the absence of differences in experimental group members between the tribal and remote testing methods of self-awareness and differences in group members for testing between the two pre-test and post- test of stress. The researcher recommends that self-awareness and stress in the adolescent group should be addressed through the psychodrama -based counseling programs.    


1977 ◽  
Author(s):  
H. Yamazaki ◽  
T. Motomiya ◽  
M. Sonoda ◽  
N. Miyagawa

Substantial clinical evidence indicates that large doses of estrogen frequenly result in thromboembolic disorders. Effects of estrogen on platelet aggregability were examined in women with uterine myoma before and after oophorectomy. Bilateral oophorectomy on 15 cases (48.7+0.12 yrs, mean+SE) and unilateral or no oophorectomy on 18 cases (control group : 42.2+0.18 yrs) were performed with myomectomy of the uterus. On one day before and one day, one week and one month after the operation performed, their platelet count by Coulter counter, platelet volume by Coulter channelyzer and platelet aggregability by Sienco aggregometer were measured. 24 hrs total estrogen in urine was also determined. In the control group, platelet counts were 85.1+ 4.9 % of the preoperated value one day after, 127.9+9.0 % one week after and 98.1+7.6 % one month after the operation. In the bilateral oophorectomy group, these were 82.4+5.2 % one day after, 124.0+4.7 % one week after and 96.1+4.8 % one month after. Both the groups showed the same change. Platelet aggregability by 3 μM ADP were 76.9+14.3 % one day after, 203.0+57.1 % one week after and 193.4+59.0 % one month after in the control, while 55.0+13.6 % one day after, 102.5+12.9 % one week after and 60.6+14.7 % one month after the operation in the total oophorectomy group. There was a statistically significant difference in the values obtained one month after the operation between the groups (p<0.05). Characteristic changes in platelet volumes were also observed. A significant correlation was observed between the platelet aggre-gabilities and the daily urinary estrogen excretion levels. The above results suggest that estrogen may enhance platelet aggregability in vivo.


Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1838 ◽  
Author(s):  
Jessica Bridoux ◽  
Sara Neyt ◽  
Pieterjan Debie ◽  
Benedicte Descamps ◽  
Nick Devoogdt ◽  
...  

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE−/− mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3566
Author(s):  
Federica Gaiani ◽  
Sara Graziano ◽  
Fatma Boukid ◽  
Barbara Prandi ◽  
Lorena Bottarelli ◽  
...  

The reasons behind the increasing prevalence of celiac disease (CD) worldwide are still not fully understood. This study adopted a multilevel approach (in vitro, ex vivo, in vivo) to assess the potential of gluten from different wheat varieties in triggering CD. Peptides triggering CD were identified and quantified in mixtures generated from simulated gastrointestinal digestion of wheat varieties (n = 82). Multivariate statistics enabled the discrimination of varieties generating low impact on CD (e.g., Saragolla) and high impact (e.g., Cappelli). Enrolled subjects (n = 46) were: 19 healthy subjects included in the control group; 27 celiac patients enrolled for the in vivo phase. Celiacs were divided into a gluten-free diet group (CD-GFD), and a GFD with Saragolla-based pasta group (CD-Sar). The diet was followed for 3 months. Data were compared between CD-Sar and CD-GFD before and after the experimental diet, demonstrating a limited ability of Saragolla to trigger immunity, although not comparable to a GFD. Ex vivo studies showed that Saragolla and Cappelli activated immune responses, although with great variability among patients. The diverse potential of durum wheat varieties in triggering CD immune response was demonstrated. Saragolla is not indicated for celiacs, yet it has a limited potential to trigger adverse immune response.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Xun Wang ◽  
Yongheng Huang ◽  
Shiwen Yuan ◽  
Amin Tamadon ◽  
Shulan Ma ◽  
...  

Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA) and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimentalin vivostudy, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS), and ovariectomy and CUS combination groups. After week 6, all groups were subdivided to three subgroups of control, EA, and estradiol treatment. The behavioral parameters in the open field and the elevated plus maze tests were assessed before and after treatments. Alterations of serum steroid hormones and changes of estradiol receptor-α(ER-α) immunofluorescence neurons in the hippocampus sections were evaluated. EA treatment caused more antianxiety effects than estradiol treatment in CUS group (P<0.05). Notably, estradiol and EA treatments had better significant behavioral effects when the models were not estrogen-deficient. Importantly, within each group, compared to the control group, the numbers of ER-α-positive neurons were significantly larger in EA subgroups. Therefore, EA had antianxiety effects on perimenopausal affective disorders caused by CUS but not by estrogen deficiency and upregulation of hippocampus ER-αneurons may contribute to its mechanism of action.


2021 ◽  
Vol 33 (6) ◽  
pp. 1433-1438
Author(s):  
R. Verma ◽  
N. Singh ◽  
P. Chaudhuri (Chattopadhyay)

The native three-dimensional structure of protein is quite unstable under critical destabilizing conditions. In order to enhance the stability and activity for a proper folded environment of a protein, many stabilizing materials are added such as nanoparticles and osmolytes to an unfolded state of protein. Osmolytes are the important group of molecules which are engaged by the cell as an adaption in the severe conditions. In this communication, a comparative in vivo study is reported for imparting the status of stability and folding ability of zebrafish dihydrofolate reductase (zDHFR) protein with gold nanoparticles and various osmolytes (glycerol, glucose and betain). Present observations revealed that the interaction of gold nanoparticles (AuNPs) with bacteria at the cellular level helps in maintaining the stability of protein more effectively than osmolytes which could be used for many biological and pharmacological approaches although glycerol as an osmolyte also stabilizes the protein at a significant level.


2018 ◽  
Vol 11 (2) ◽  
pp. 13-18 ◽  
Author(s):  
Vitaly V. Potyomkin ◽  
Tatyana S. Varganova ◽  
Irina V. Terehova ◽  
Elena V. Ageeva

Phacoemulsification (PE) is the leading method of cataract surgery. Purpose. To assess the impact of PE on corneal subbasal nerve plexus in patients with pseudoexfoliation syndrome (PEX) using confocal in vivo microscopy. Methods. 42 patients (42 eyes) were enrolled in the study. The main group consisted of 24 patients (24 eyes) with PEX syndrome, and 18 patients (18 eyes) without it composed the control group. Confocal in vivo microscopy was performed before and after PHACO. Results. In patients with PEX after PE, an increase in number of nerve branches and pellet-like structures in them were noticed (p < 0,05).


2016 ◽  
Vol 28 (2) ◽  
pp. 161
Author(s):  
D. Scarlet ◽  
N. Ille ◽  
G. D. A. Gastal ◽  
B. G. Alves ◽  
S. O. Paiva ◽  
...  

Glucocorticoids are mediators of the systemic stress response. Acute or chronic stress characterised by high cortisol concentrations in the periphery impairs reproductive function in a variety of species and therefore may affect fertility. The ovary has been shown to be a target tissue for glucocorticoids in many species, including the mare. This study hypothesised that the equine ovary possesses internal mechanisms to modulate cortisol activity and that supraphysiologic levels of glucocorticoids do not affect oocyte IVM rates. Light horse mares (n = 9) were used in this study. Growing follicles from an induced follicular wave were divided into the following groups: G1: 5–9 mm, G2: 10–14 mm, G3: 15–19 mm, G4: 20–24 mm, and G5: ≥25 mm. Follicular fluid (FF) and compact cumulus‐oocyte complexes (COCs) were obtained by ultrasound-guided transvaginal aspiration. Blood samples were collected at the beginning and the end of every aspiration session. Cortisol (DE1887, Demeditec, Kiel-Wellsee, Germany), progesterone (ADI-901–011, Enzo Life Sciences, Farmingdale, NY, USA), and corticosteroid binding globulin (CBG, MBS047353, MyBioSource, San Diego, CA, USA) concentrations were determined by ELISA. COCs (n = 80) were randomly distributed to either the control group (DMEM-F12+ medium) or the following hydrocortisone treatment groups: 0.1 µg mL–1, 1 µg mL–1, 5 µg mL–1, 10 µg mL–1. Maturation rate was assessed 30 h after incubation. Statistical analysis was performed with the SPSS Statistics 22 software. Data were analysed using one-way ANOVA, Pearson correlation, and chi-squared test. Cortisol (115.4 ± 13.3 ng mL–1) and progesterone (22.1 ± 3.1 ng mL–1) FF concentrations were higher (P < 0.05) in G5 follicles than in all other groups, and were positively correlated (r = 0.8; P < 0.001). Plasma concentrations of cortisol (118.6 ± 7.8 v. 120.3 ± 12.2 ng mL–1), progesterone (2.4 ± 0.5 v. 2.5 ± 0.4 ng mL–1), and CBG (11.1 ± 5.1 v. 9.9 ± 3.2 µg mL–1) did not differ before and after follicle aspiration. However, plasma CBG and progesterone were negatively correlated (r = –0.56; P < 0.01). Maturation rates did not differ among groups, regardless of the hydrocortisone concentration added to the culture medium. Our results demonstrated higher cortisol concentrations in preovulatory follicles in vivo, suggesting its importance for oocyte maturation. The greater unbound cortisol available in the FF of preovulatory follicles can be indicative of the displacement of cortisol from CBG in favour of progesterone. Furthermore, equine oocytes were capable of surviving cortisol concentrations 100 times higher than those physiologically present in preovulatory follicles. This finding suggests the ability of equine oocytes to modulate cortisol levels and adapt to stress situations.


2001 ◽  
Vol 100 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Anita ZETTERLUND ◽  
Paul HJEMDAHL ◽  
Kjell LARSSON

In vitro studies suggest that glucocorticoids may counteract β-agonist-induced desensitization of β-adrenoceptors by actions at the transcriptional level, but the clinical relevance of such findings is not clear. Oral terbutaline treatment decreases β-adrenoceptor sensitivity in alveolar macrophages in vivo. This effect is not counteracted by inhaled or orally taken steroids. We therefore examined whether inhaled terbutaline elicited a similar effect on β2-adrenoceptor sensitivity in alveolar macrophages, and if co-treatment with an inhaled steroid, budesonide, would prevent such down-regulation. Bronchoalveolar lavage (BAL) and lung function tests, including bronchodilator responses to inhaled terbutaline, were performed before and after 2 weeks of regular inhalation of terbutaline, 0.5 mg three times daily, and budesonide, 400 µg twice daily, or placebo, in 24 healthy volunteers. Four untreated subjects served as controls. A marked, approx. 90%, decrease in isoprenaline-induced cAMP accumulation in alveolar macrophages was found in both treatment groups after 2 weeks, with no difference between placebo and budesonide (P = 0.45). In the untreated control group, cAMP responses to both isoprenaline and prostaglandin E1 tended to be lower on the second occasion. A limited, non-specific desensitization of adenylate cyclase activity thus contributed to the marked desensitization elicited by terbutaline inhalations. The bronchodilator response to inhaled terbutaline did not change after treatment in any of the three groups (F = 0.9, P = 0.50). In conclusion, inhalation of a β-agonist induced marked down-regulation of β2-adrenoceptor sensitivity in alveolar macrophages in vivo without influencing the bronchodilator response to a β2-agonist in healthy subjects. Co-treatment with an inhaled steroid failed to counteract the desensitization of alveolar macrophage β2-adrenoceptors.


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