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1.
Lifestyle Genom ; 16(1): 214-223, 2023.
Article in English | MEDLINE | ID: mdl-37879306

ABSTRACT

INTRODUCTION: Single-nucleotide polymorphism (SNP) rs9939609 in the FTO gene has been associated with dietary intake and appetite traits, mainly in participants with obesity; however, it remains widely unexplored in normal weight participants. Thus, the aims of this study were (1) to compare the changes in subjective appetite sensations, ghrelin, and insulin concentrations according to the SNP rs9939609 T>A in FTO and (2) to compare dietary intake between rs9939609 genotype groups in normal weight young participants. METHODS: We conducted a quasi-experimental study involving 88 normal weight participants to analyze subjective perception of appetite, hormonal response for hunger and satiety, and dietary intake according to the rs9939609 SNP. Participants received a standardized single breakfast. Visual analogue scales (VAS) were utilized for assessing the subjective perception of appetite at fasting and immediately after breakfast and at 30, 60, 90, and 120 min postprandially. Glucose, lipid profile, ghrelin, and insulin were measured at fasting and at 120 min after breakfast. Dietary intake was assessed with a 3-day food record. The SNP was determined by allelic discrimination with TaqMan probes. To compare dietetic, biochemical, and the subjective appetite sensations, Student t test, ANCOVA test, and the repeated measures ANOVA were used. The linear regression model and the linear mixed model were used for the association analysis. Pearson correlation was used to test the correlation between two quantitative variables. RESULTS: A total of 88 people participated, 81.8% were female, with a mean body mass index of 21.8 ± 2.0 kg/m2 and a mean age of 20.6 ± 2.0. Genotype frequencies of the rs9939609 SNP were 52% for the TT allele and 48% for the TA/AA. The subjective perception of appetite named hunger, fullness, satiety, desire to eat, and prospective food consumption were similar between genotypes of the rs9939609. Participants with the TA/AA genotype showed a higher intake of added sugar (p = 0.039) than TT participants. No differences were found in ghrelin, insulin, glucose, or lipid parameters between genotypes. CONCLUSION: Carriers of the A allele from FTO gene SNP rs9939609 may have an increased preference for foods, specifically for added sugars.


Subject(s)
Ghrelin , Insulin , Humans , Female , Young Adult , Adolescent , Adult , Male , Ghrelin/genetics , Genotype , Glucose , Lipids , Sugars , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
2.
Physiol Behav ; 254: 113878, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35700814

ABSTRACT

Several factors, including environmental modifications, stimulate neuroplasticity. One type of neuroplasticity consists in the generation of new neurons in the dentate gyrus of the hippocampus. Neurogenesis is modulated by environmental enrichment (ENR, tunnels plus running wheel) and affected by the time of exposure to ENR. Despite the wide use of ENR to stimulate neuroplasticity, the degree to which ENR variations modeled by temporally changing the level of environmental complexity affect hippocampal neurogenesis and anxiety is still unclear. Thus, we investigated the effects of five housing conditions on young adult male Balb/C mice exposed for 42 days. The groups were as follows: standard conditions without ENR, constant ENR complexity, gradual increase of ENR complexity followed by a gradual decrease of ENR complexity, gradual increase of ENR complexity followed by constant ENR complexity, and constant ENR complexity followed by a gradual decrease of ENR complexity. On day 44, mice were exposed to the elevated plus-maze to evaluate anxiety. Further, we analyzed neurogenesis and quantified corticosterone levels. In an additional experiment, we explored the effect of voluntary physical activity on anxiety, neurogenesis, and corticosterone during the variations in ENR complexity. Our results showed that any change in ENR complexity over time reduced anxiety. Also, voluntary physical activity alone or in the context of a complex environment increased doublecortin cell maturation in the granular cell layer of the hippocampus. Finally, our study supports that physical activity acts proneurogenic, whereas any change in environmental complexity decreases anxiety-like behavior. However, the decrease in corticosterone levels elicited by physical activity was lower than the decrease produced by the decrement in environmental complexity.


Subject(s)
Corticosterone , Environment , Animals , Anxiety , Hippocampus/physiology , Male , Mice , Mice, Inbred BALB C , Neurogenesis/physiology
3.
Sci Total Environ ; 815: 152760, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34990689

ABSTRACT

The aim of this work was to study the absorption, distribution through the hemolymph, and bioaccumulation of arsenic by the freshwater Pomacea canaliculata using a short-lived tracer (76As, t1/2: 1.07 d) with high specific activity. Arsenic travels mainly dissolved in the plasma of the snail's hemolymph. This element is transferred from the hemolymph to the tissues (87%) 4 h after the inoculation of 50 µL of a 0.04 g/L of 76As radiotracer solution, being the digestive gland, kidney, and head-foot the main places of arsenical inventories. Snails exhibited a rapid arsenic accumulation response in a wide range of concentrations (from 1 to 1000 µg/L) of the metalloid dissolved in water and in a concentration-dependent manner. Also, snails incorporated As from the digestive system when they received a single safe dose of ~2 µg of 76As inoculated in a fish food pellet. The (semi) physiologically based toxicokinetic model developed in this study is based on anatomical and physiological parameters (blood flow, irrigation, tissue volume and other). Together, these findings make P. canaliculata an excellent sentinel organism to evaluate freshwater bodies naturally contaminated with As.


Subject(s)
Arsenic , Animals , Environmental Biomarkers , Hemolymph , Radioisotopes , Snails
4.
Diagnostics (Basel) ; 10(11)2020 Nov 22.
Article in English | MEDLINE | ID: mdl-33266467

ABSTRACT

The objective of the study was to describe a case-series of neural tube defects (NTD) with an abnormal intracranial translucency (IT) detected during the first-trimester ultrasound scan, performed on a low-risk obstetric population in Mexico. Certified Fetal Medicine specialists performed all US scans; the IT was assessed using the mid-sagittal view of the fetal head, which is already systematically used for nuchal translucency and nasal bone evaluation. During the study, we were able to find that eight fetuses had an absence of the intracranial translucency, out of which two were reassessed at 14 weeks' gestation and IT was normal, six of them were later diagnosed to have an NTD that consisted in spina bifida aperta (n = 5) and encephalocele (n = 1). Conclusion: As previous studies have shown, IT evaluation during the first-trimester US routine scan may be a useful screening marker for early detection of NTDs.

5.
J Avian Med Surg ; 34(2): 152-157, 2020 Jul 21.
Article in English | MEDLINE | ID: mdl-32702954

ABSTRACT

A total of 356 gyrfalcon (Falco rusticolus) fecal, fomite, and environmental samples were collected from a breeding center located in the United Arab Emirates to assess the prevalence of Caryospora species oocysts in the environment. These included 136 samples (38%) from fomites and fecal samples from chicks at 0 to 10 days old, 29 samples (8%) at 15 days old, 23 samples (6%) at 60 days old, 7 samples (2%) at 67 days old, and 24 samples (7%) at 70 days old. In addition, 105 samples (29%) were collected from the environment of 13 breeding chambers, and 32 samples (9%) from the environment of 17 juvenile falcons. The prevalence of Caryospora species oocysts in fomites and fecal samples from the chicks had negative results from 10 to 60 days old. However, at 67 and 70 days old, the prevalence increased to 71.42% (5 of 7) and 95.83% (23 of 24), respectively. The prevalence of Caryospora species in the environment of 13 pairs of falcons housed in 13 breeding chambers was 0.15 oocyst/m2 in the sand, whereas, in the environment of 17 juvenile falcons housed in the free-flying aviary, the prevalence was 0.00086 oocyst/m2 in the sand and 0.15 oocyst/L in contaminated water. These results indicate that oocysts of Caryospora species may be found in the environment and in areas of poor and substandard hygiene. Caryospora species is an important protozoon parasite affecting captive falcons maintained in breeding centers and those used for falconry in the Middle East.


Subject(s)
Animal Husbandry , Bird Diseases/epidemiology , Coccidiosis/veterinary , Eimeriidae/isolation & purification , Falconiformes , Animals , Breeding , Coccidiosis/epidemiology , Environment , Feces/parasitology , Prevalence , United Arab Emirates/epidemiology
6.
Neuroscience ; 440: 316-336, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32417342

ABSTRACT

Depression may be precipitated by the negative impact of chronic stress, which is considered to play a key role in this neuropsychiatric disorder. Interestingly, depressed patients show decreased levels of melatonin. This hormone acts pro-neurogenic and exhibits anti-depressant effects in rodent models of predictive antidepressant-like effects. However, the benefits of melatonin in reversing the deleterious effects of chronic mild stress on the alterations in behaviour and in the neurogenic niche of the hippocampus in male BALB/c mice are unknown. In this study, we compared the effects of melatonin (2.5 mg/kg) and citalopram (5 mg/kg), an antidepressant drug belonging to the selective serotonin reuptake inhibitors, in male BALB/c mice exposed to chronic mild stress (CMS). We also investigated the potential effects of melatonin and citalopram on microglial cells, hippocampal neurogenesis and peripheral cytokine profiles. Melatonin and citalopram induced similar antidepressant-like activities that occurred with some of the the following findings: (1) reversal of the morphological alterations in microglia; (2) reversal of the decreased immunoreactivity to CX3CL1 and CX3CR1 in the dentate gyrus; (3) positive regulation of cell proliferation, survival and complexity of the dendritic trees of doublecortin-cells; and (4) modifications of peripheral CX3CL1 expression. This outcome is consistent with the hypothesis about the antidepressant-like effect of melatonin and supports its relevance as a modulator of the niche in the dentate gyrus.


Subject(s)
Chemokine CX3CL1 , Melatonin , Animals , Depression/drug therapy , Hippocampus , Male , Melatonin/pharmacology , Mice , Mice, Inbred BALB C , Microglia , Neurogenesis
7.
Curr Med Mycol ; 6(4): 62-65, 2020 Dec.
Article in English | MEDLINE | ID: mdl-34195462

ABSTRACT

BACKGROUND AND PURPOSE: Tinea gladiatorum is a type of dermatophytosis that occurs in combat athletes, such as wrestlers and judo fighters, as a result of Trichophyton species. Herein, we aimed to present a small outbreak of tinea gladiatorum in a high school in Mexico. MATERIALS AND METHODS: Seven individuals belonging to the school fighting team were mycologically studied with direct examinations and cultures. In four cases, T. tonsurans was isolated and identified by morphological and proteomic methods (Matrix-assisted laser desorption/ionization- time-of-flight mass spectrometry). Out of the four subjects, two cases had clinical lesions presented as tinea corporis, and two cases were healthy carriers. Trichophyton tonsurans was also isolated from one of the four training mats (25%). All positive patients were treated with systemic or topical antifungals and achieved clinical and mycological cure. CONCLUSION: We report the first outbreak of tinea gladiatorum caused by T. tonsurans among a group of high school wrestlers in Mexico.

8.
Rev. bras. entomol ; 64(1): e2018131, 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1092592

ABSTRACT

Abstract The Eriococcidae (Hemiptera: Coccomorpha), are known as felt scales and a family with a worldwide distribution, represented by 33 genera and 92 species in the Neotropical region. Some of these species induce galls on their host plants. The aim of this study is to review and update all the information currently known about the biodiversity of Eriococcidae in Brazil and to redescribe and illustrate Acanthococcus lanatus (Hempel), Acanthococcus campinensis (Hempel) and Neotectococcus lenticularis Hempel because Hempel's original descriptions are very brief and he made no illustrations, and to describe a new species of Acanthococcus Signoret, Acanthococcus papaveroi González, Claps & Juárez sp. nov. A dichotomous key to the Acanthococcus species from Brazil is presented and an updated table of the Eriococcidae known from this country is included, with 34 species and 16 genera in total, each with distribution, host data and type depositories of each species.

9.
Acta Ortop Bras ; 26(4): 218-221, 2018.
Article in English | MEDLINE | ID: mdl-30210247

ABSTRACT

OBJECTIVE: The aim of this study is to estimate the inter- and intra-observer agreement of the Weiss and Milch classification systems in radiological studies of fractures of the lateral humeral condyle in pediatric patients. METHODS: An agreement study was performed with non-probability sampling of consecutive cases with a sample size of a hundred radiological studies, which were evaluated by three experienced orthopedic surgeons and three resident physicians; following a thorough comparison of both inter- and intra-observer agreements over a six-week period based on the Fleiss' kappa, which was used to determine the inter- and intra-observer agreement rates of both classifications. RESULTS: The overall reliability of the entire group of evaluators for the Milch classification in the inter-observer evaluation was κ = 0.13, 95% CI, 0.08-0.18, and the intra-observer evaluation was κ = 0.08, 95% CI, 0.06-0.11. For the Weiss classification, the overall evaluation had an inter-observer agreement of κ = 0.53, 95% CI, 0.50-0.57, and an intra-observer agreement of κ = 0.22, 95% CI, 0.20 -0.24. CONCLUSION: In the present study, the Weiss classification system demonstrated greater agreement than the Milch classification; however, the latter may require complementary studies, such as an arthrography to enhance classification accuracy. Level of Evidence II, Diagnostic Studies - Investigating Diagnostic Examination.


OBJETIVO: Este estudo visa estimar a concordância intra e interobservador da classificação de Weiss e Milch, em estudos radiológicos de pacientes pediátricos com fratura da parte lateral do côndilo do úmero. MÉTODOS: Estudo de concordância realizado com amostragem não probabilística de casos consecutivos com amostra de cem estudos radiológicos que foram avaliados por três observadores especialistas e por três médicos residentes; depois de uma comparação completa da concordância inter e intraobservador durante seis semanas, com base no kappa de Fleiss, que foi usado para determinar a concordância inter e intraobservador das duas classificações. RESULTADOS: A confiabilidade global de todo o grupo de avaliadores da classificação de Milch na avaliação interobservador foi κ = 0,13, IC 95% 0,08-0,18 e intraobservador foi κ = 0,08, IC 95% 0,06-0,11. A avaliação geral da classificação de Weiss obteve concordância interobservador de κ = 0,53, IC 95% 0,50-0,57 e intraobservador de κ = 0,22, IC 95% 0,20-0,24. CONCLUSÃO: No presente estudo, o sistema de classificação de Weiss mostrou concordância maior do que a classificação Milch; contudo, esta última pode exigir estudos complementares, como artrografia, para ampliar a acurácia da classificação. Nível de Evidência II, Estudos Diagnósticos - Investigação de um Exame para Diagnóstico.

10.
Int J Biol Macromol ; 120(Pt A): 566-577, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30145160

ABSTRACT

Plant lectins have been studied owing to their structural properties and biological effects that include agglutinating activity, antidepressant-like effect and antitumor property. The results from this work showed the effects of the lectin extracted from the Dioclea violacea plant (DVL) on the C6 rat glioma cell line. DVL treatment was able to induce caspase-3 activation, apoptotic cell death and cellular membrane damage. Furthermore, DVL decreased mitochondrial membrane potential and increased the number of acidic vesicles and cleavage of LC3, indicating activation of autophagic processes. DVL also significantly inhibited cell migration. Compared to ConA, a well-studied lectin extracted from Canavalia ensiformes seeds, some effects of DVL were more potent, including decreasing C6 glioma cell viability and migration ability. Taken together, the results suggest that DVL can induce glioma cell death, autophagy and inhibition of cell migration, displaying potential anti-glioma activity.


Subject(s)
Autophagy/drug effects , Dioclea/chemistry , Gene Expression/drug effects , Neuroglia/drug effects , Plant Lectins/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/genetics , Autophagy/genetics , Canavalia/chemistry , Caspase 3/genetics , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Cell Movement/drug effects , Cell Proliferation/drug effects , Concanavalin A/isolation & purification , Concanavalin A/pharmacology , L-Lactate Dehydrogenase/metabolism , Membrane Potential, Mitochondrial/drug effects , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Neuroglia/metabolism , Neuroglia/pathology , Plant Lectins/isolation & purification , Rats
11.
Acta ortop. bras ; 26(4): 218-221, July-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-973562

ABSTRACT

ABSTRACT Objective: The aim of this study is to estimate the inter- and intra-observer agreement of the Weiss and Milch classification systems in radiological studies of fractures of the lateral humeral condyle in pediatric patients. Methods: An agreement study was performed with non-probability sampling of consecutive cases with a sample size of a hundred radiological studies, which were evaluated by three experienced orthopedic surgeons and three resident physicians; following a thorough comparison of both inter- and intra-observer agreements over a six-week period based on the Fleiss' kappa, which was used to determine the inter- and intra-observer agreement rates of both classifications. Results: The overall reliability of the entire group of evaluators for the Milch classification in the inter-observer evaluation was κ = 0.13, 95% CI, 0.08-0.18, and the intra-observer evaluation was κ = 0.08, 95% CI, 0.06-0.11. For the Weiss classification, the overall evaluation had an inter-observer agreement of κ = 0.53, 95% CI, 0.50-0.57, and an intra-observer agreement of κ = 0.22, 95% CI, 0.20 −0.24. Conclusion: In the present study, the Weiss classification system demonstrated greater agreement than the Milch classification; however, the latter may require complementary studies, such as an arthrography to enhance classification accuracy. Level of Evidence II, Diagnostic Studies - Investigating Diagnostic Examination.


RESUMO Objetivo: Este estudo visa estimar a concordância intra e interobservador da classificação de Weiss e Milch, em estudos radiológicos de pacientes pediátricos com fratura da parte lateral do côndilo do úmero. Métodos: Estudo de concordância realizado com amostragem não probabilística de casos consecutivos com amostra de cem estudos radiológicos que foram avaliados por três observadores especialistas e por três médicos residentes; depois de uma comparação completa da concordância inter e intraobservador durante seis semanas, com base no kappa de Fleiss, que foi usado para determinar a concordância inter e intraobservador das duas classificações. Resultados: A confiabilidade global de todo o grupo de avaliadores da classificação de Milch na avaliação interobservador foi κ = 0,13, IC 95% 0,08-0,18 e intraobservador foi κ = 0,08, IC 95% 0,06-0,11. A avaliação geral da classificação de Weiss obteve concordância interobservador de κ = 0,53, IC 95% 0,50-0,57 e intraobservador de κ = 0,22, IC 95% 0,20-0,24. Conclusão: No presente estudo, o sistema de classificação de Weiss mostrou concordância maior do que a classificação Milch; contudo, esta última pode exigir estudos complementares, como artrografia, para ampliar a acurácia da classificação. Nível de Evidência II, Estudos Diagnósticos - Investigação de um Exame para Diagnóstico.

12.
Zootaxa ; 4232(1): zootaxa.4232.1.3, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28264378

ABSTRACT

Three new species of Eriococcidae from Argentina, namely Acanthococcus haywardi Juárez & González sp. nov., A. punctatae Juárez & González sp. nov. and A. riojensis Juárez & González sp. nov., are described and illustrated, bringing the total number of eriococcid species now known from Argentina to 12, of which six belong to Acanthococcus Signoret and six to Hempelicoccus Kozár. They are found on 11 species of Fabaceae (subfamilies Mimosoideae and Caesalpinioidae), are widely distributed and are all restricted to the Neotropical region and the South American Transitional Zone. A key to the 12 Eriococcidae species now known on Fabaceae in Argentina is included.


Subject(s)
Hemiptera , Animal Structures , Animals , Argentina , Fabaceae , Organ Size
13.
Environ Sci Pollut Res Int ; 23(18): 17995-8009, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27255321

ABSTRACT

Vegetation associated with lacustrine systems in Northern Patagonia was studied for heavy metal and trace element contents, regarding their elemental contribution to these aquatic ecosystems. The research focused on native species and exotic vascular plant Salix spp. potential for absorbing heavy metals and trace elements. The native species studied were riparian Amomyrtus luma, Austrocedrus chilensis, Chusquea culeou, Desfontainia fulgens, Escallonia rubra, Gaultheria mucronata, Lomatia hirsuta, Luma apiculata, Maytenus boaria, Myrceugenia exsucca, Nothofagus antarctica, Nothofagus dombeyi, Schinus patagonicus, and Weinmannia trichosperma, and macrophytes Hydrocotyle chamaemorus, Isöetes chubutiana, Galium sp., Myriophyllum quitense, Nitella sp. (algae), Potamogeton linguatus, Ranunculus sp., and Schoenoplectus californicus. Fresh leaves were analyzed as well as leaves decomposing within the aquatic bodies, collected from lakes Futalaufquen and Rivadavia (Los Alerces National Park), and lakes Moreno and Nahuel Huapi (Nahuel Huapi National Park). The elements studied were heavy metals Ag, As, Cd, Hg, and U, major elements Ca, K, and Fe, and trace elements Ba, Br, Co, Cr, Cs, Hf, Na, Rb, Se, Sr, and Zn. Geochemical tracers La and Sm were also determined to evaluate contamination of the biological tissues by geological particulate (sediment, soil, dust) and to implement concentration corrections.


Subject(s)
Aquatic Organisms/chemistry , Metals, Heavy/analysis , Plant Leaves/chemistry , Salix/chemistry , Trace Elements/analysis , Argentina , Ecosystem , Environmental Monitoring , Lakes , Mercury/analysis , Trees/chemistry
14.
J Photochem Photobiol B ; 153: 445-54, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26569453

ABSTRACT

Several research efforts have been focused on finding newer and more efficient photosensitizers for photodynamic therapy (PDT). Although, it was demonstrated that riboflavin is an efficient photosensitizer for PDT, the effect of its ester derivate, riboflavin 2',3',4',5'-tetraacetate (RFTA), which has higher cellular uptake, has not been well defined. To evaluate the cell death generated by applying RFTA as the photosensitizer in PDT in a human cancer cell line of squamous carcinoma (SCC-13), these cells were incubated with riboflavin and its ester derivate, RFTA followed by irradiation with different blue light doses. Cell viability was evaluated using neutral red uptake assay and cell death was evaluated using transmission electron microscopy, TUNEL assay and annexin V-PE/7AAD double staining. The expression of caspase-3, Bax, Bcl-2, ERK 1/2 and p38(MAPK) was evaluated by Western blotting and generation of intracellular ROS and changes in anion superoxide levels were analyzed using 2',7'-dichlorofluorescein-diacetate and dihydroethidium dye, respectively. RFTA-PDT generated a decrease in cancer cell viability in a light dose-response. Treated SCC-13 cells exhibited chromatin condensation, formation of apoptotic bodies, increases in TUNEL-positive cells, phosphatidylserine externalization and decreased procaspase-3 and Bcl-2 protein expression and increment of ERK 1/2 phosphorylation. Moreover, trolox abolished the effect of PDT on cell viability linking the increase in intracellular ROS levels with the cell death observed, whereas that the pre-treatment with MEK inhibitor did not induce changes in SCC-13 cell survival. These findings demonstrate the effects of RFTA in triggering apoptosis induced by ROS (\O2(-)) production after visible light irradiation of squamous carcinoma cells.


Subject(s)
Apoptosis/drug effects , Photosensitizing Agents/pharmacology , Riboflavin/analogs & derivatives , Riboflavin/pharmacology , Apoptosis/radiation effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Caspase 3/metabolism , Cell Line , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , DNA Fragmentation/drug effects , DNA Fragmentation/radiation effects , Humans , Light , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Riboflavin/chemistry , Riboflavin/therapeutic use , bcl-2-Associated X Protein/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
15.
J Biomed Nanotechnol ; 10(3): 393-404, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24730235

ABSTRACT

Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of alpha(v)beta(3) integrin, thereby inhibiting angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable multimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of 177Lu-AuNP-RGD in athymic mice bearing alpha(v)beta(3)-integrin-positive C6 gliomas and compare it with that of 177Lu-AuNP or 177Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-microPET/CT), histological characteristics and VEGF gene expression (by real-time polymerase chain reaction) in tumor tissues following treatment with 177Lu-AuNP-RGD, 177Lu-AuNP or 177Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 1177Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 +/- 7.9 Gy). These results correlated with the observed therapeutic response, in which 177Lu-AuNP-RGD significantly (p < 0.05) induced less tumor progression, less tumor metabolic activity, fewer intratumoral vessels and less VEGF gene expression than the other radiopharmaceuticals, a consequence of high tumor retention and a combination of molecular targeting therapy (multimeric RGD system) and radiotherapy (177Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177Lu-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular targeting radiotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Chemoradiotherapy/methods , Gold/therapeutic use , Lutetium/therapeutic use , Metal Nanoparticles/therapeutic use , Molecular Targeted Therapy/methods , Nanoconjugates/therapeutic use , Neoplasms/radiotherapy , Peptides, Cyclic/therapeutic use , Radioisotopes/therapeutic use , Animals , Antineoplastic Agents/chemistry , Cells, Cultured , Lutetium/chemistry , Male , Mice , Mice, Nude , Neovascularization, Pathologic , Peptides, Cyclic/chemistry , Radioisotopes/chemistry , Rats , Xenograft Model Antitumor Assays
16.
Dalton Trans ; 41(46): 14051-4, 2012 Dec 14.
Article in English | MEDLINE | ID: mdl-23085681

ABSTRACT

Two bicyclic compounds containing Arg-Gly-Asp (RGD) motifs (RGDf and RGD) were synthesized by cyclizing the peptide sequence across the macrocyclic ring of DOTA via two non-adjacent carboxylate pendent arms. The Lu(3+) or Cu(2+) complexes of these compounds, c(DOTA-RGDf) and c(DOTA-RGD), showed a metal dependent affinity towards integrin α(v)ß(3)in vitro and the (177)Lu(3+) or (64)Cu(2+) labelled derivatives showed specific tumour uptake in MCF7 and U87MG tumour bearing mice.


Subject(s)
Chelating Agents/chemistry , Heterocyclic Compounds, 1-Ring/chemistry , Integrin alphaVbeta3/metabolism , Macrocyclic Compounds/chemistry , Molecular Imaging/methods , Oligopeptides/chemistry , Oligopeptides/metabolism , Animals , Biological Transport , Cell Line, Tumor , Cyclization , Humans , Mice , Oligopeptides/chemical synthesis
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