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1.
Bioorg Med Chem ; 97: 117515, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-38043245

RESUMEN

Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging.


Asunto(s)
Receptores sigma , Neoplasias de la Mama Triple Negativas , Ratas , Ratones , Humanos , Animales , Ligandos , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Ratones Desnudos , Ácido Pentético , Receptores sigma/metabolismo , Radiofármacos , Línea Celular Tumoral , Tomografía Computarizada de Emisión de Fotón Único
2.
BMC Pregnancy Childbirth ; 23(1): 706, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37789260

RESUMEN

BACKGROUND: The updated World Health Organization (WHO) guideline recommends immediate kangaroo mother care (KMC) for all infants, particularly those born preterm. However, its uptake and sustainability have been unsatisfactory. Therefore, we aimed to gain deeper insight into factors influencing the uptake of KMC practice in our setting, and thereby identify possible solutions for the development of relevant interventions to improve its adoption and make KMC a routine practice for all infants. METHODS: Using the Triandis model of social behaviour as our framework, we conducted key informant interviews with parents and healthcare providers. Trained interviewers conducted interviews with nine parents, recruited via purposive sampling. These parents were parents of preterm infants who had been introduced to KMC. Data was transcribed and analysed based on Triandis' Theory of Interpersonal Behaviour. This paper only reports the results of the parent interviews. RESULTS: Major findings were how positive feelings like warmth and contentment, the sense of parenthood with KMC, the benefits of KMC for their infant and parents being enablers for KMC uptake. Conversely, the lack of KMC awareness, the initial negative feelings such as fear, uncertainty and embarrassment, the prioritization of time for milk expression, overcrowding in the ward, lack of space and privacy, limited visiting hours, lack of support and poor communication resulting in misapprehension about KMC were major barriers. CONCLUSION: A deeper understanding of the factors influencing the uptake of KMC using the Triandis behavioural model provided a way forward to help improve its uptake and sustainability in our settings. TRIAL REGISTRATION: This study was registered with the National Medical Research Registry (NMRR-17-2984-39191).


Asunto(s)
Recien Nacido Prematuro , Método Madre-Canguro , Lactante , Niño , Recién Nacido , Humanos , Padres , Hospitales , Personal de Salud
3.
Anticancer Agents Med Chem ; 24(7): 488-503, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38279753

RESUMEN

Over the last few decades, an alarming rise in the percentage of individuals with cancer and those with multi-resistant illnesses has forced researchers to explore possibilities for novel therapeutic approaches. Numerous medications currently exist to treat various disorders, and the development of small molecules as anticancer agents has considerable potential. However, the widespread prevalence of resistance to multiple drugs in cancer indicates that it is necessary to discover novel and promising compounds with ideal characteristics that could overcome the multidrug resistance issue. The utilisation of metallo-drugs has served as a productive anticancer chemotherapeutic method, and this approach may be implemented for combating multi-resistant tumours more successfully. Schiff bases have been receiving a lot of attention as a group of compounds due to their adaptable metal chelating abilities, innate biologic properties, and versatility to tweak the structure to optimise it for a specific biological purpose. The biological relevance of Schiff base and related complexes, notably their anticancer effects, has increased in their popularity as bio-inorganic chemistry has progressed. As a result of learning about Schiff bases antitumor efficacy against multiple cancer cell lines and their complexes, researchers are motivated to develop novel, side-effect-free anticancer treatments. According to study reports from the past ten years, we are still seeking a powerful anticancer contender. This study highlights the potential of Schiff bases, a broad class of chemical molecules, as potent anticancer agents. In combination with other anticancer strategies, they enhance the efficacy of treatment by elevating the cytotoxicity of chemotherapy, surmounting drug resistance, and promoting targeted therapy. Schiff bases also cause cancer cell DNA repair, improve immunotherapy, prevent angiogenesis, cause apoptosis, and lessen the side effects of chemotherapy. The present review explores the development of potential Schiff base and their d and f block metal complexes as anticancer agents against various cancer cell lines.


Asunto(s)
Antineoplásicos , Proliferación Celular , Complejos de Coordinación , Bases de Schiff , Bases de Schiff/química , Bases de Schiff/farmacología , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Proliferación Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-Actividad , Animales
4.
Int J Gynaecol Obstet ; 160 Suppl 1: 50-55, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36635080

RESUMEN

Obesity has been linked to infertility through several mechanisms, including at a molecular level. Those living with obesity face additional barriers to accessing fertility treatments and achieving a successful pregnancy, which can contribute to their economic and psychosocial stressors. There is scope to further improve care for people living with obesity and infertility with empathy, via a multidisciplinary approach.


Asunto(s)
Fertilidad , Infertilidad , Femenino , Humanos , Embarazo , Infertilidad/etiología , Infertilidad/terapia , Infertilidad/psicología , Obesidad/complicaciones , Obesidad/terapia , Técnicas Reproductivas Asistidas
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