Near Infrared Biomimetic Hybrid Magnetic Nanocarrier for MRI-Guided Thermal Therapy.

Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM-1s-1, decreasing respectively to 445 mM-1s-1 and 278 mM-1s-1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r2/r1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

Glycine transporter-1 inhibition by NFPS promotes neuroprotection against striatal damage models.

The striatum, an essential component of the brain's motor and reward systems, plays a pivotal role in a wide array of cognitive processes. Its dysfunction is a hallmark of neurodegenerative diseases like Parkinson's disease (PD) and Huntington's disease (HD), leading to profound motor and cognitive deficits. These conditions are often related to excitotoxicity, primarily due to overactivation of NMDA receptors (NMDAR). In the synaptic cleft, glycine transporter type 1 (GlyT1) controls the glycine levels, a NMDAR co-agonist, which modulates NMDAR function. This research explored the neuroprotective potential of NFPS, a GlyT1 inhibitor, in murine models of striatal injury. Employing models of neurotoxicity induced by 6-hydroxydopamine (PD model) and quinolinic acid (HD model), we assessed the effectiveness of NFPS pre-treatment in maintaining the integrity of striatal neurons and averting neuronal degeneration. The results indicated that NFPS pre-treatment conferred significant neuroprotection, reducing neuronal degeneration, protecting dopaminergic neurons, and preserving dendritic spines within the striatum. Additionally, this pre-treatment notably mitigated motor impairments resulting from striatal damage. The study revealed that GlyT1 inhibition led to substantial changes in the ratios of NMDAR subunits GluN2A/GluN1 and GluN2B/GluN1, 24 h after NFPS treatment. These findings underscore the neuroprotective efficacy of GlyT1 inhibition, proposing it as a viable therapeutic strategy for striatum-related damage.

Combining the Katritzky Reaction and Paper Spray Ionization Mass Spectrometry for Enhanced Detection of Amino Acid Neurotransmitters in Mouse Brain Sections.

This work describes the development of a system that combines a derivatization protocol based on the Katritzky reaction with paper spray ionization mass spectrometry (PSI-MS) for the analysis of amino acid neurotransmitters in mouse brain tissues. The system is relatively simple, consisting of spraying the derivatization solution onto a mouse brain section mounted on a glass slide, applying a small volume of solvent to moisten the sample, pressing a triangular paper onto the sample surface to transfer the sample constituents to the paper surface, and using the paper as a substrate for PSI-MS analysis. The Katritzky reaction facilitated the ionization of the amino acids by reacting a pyrylium salt with the amino group of the analytes, forming very stable pyridinium cations, which greatly increased the sensitivity of the PSI-MS analysis. Most of the intensities of the amino acids modified by the Katritzky reaction were more than 10 times greater than the nonderivatized ones. The system was applied for the analysis of brain sections obtained from mice with Parkinson's disease, and the amino acids gamma-aminobutyric acid (GABA) and glycine (Gly), two compounds very well-known in studies of Parkinson's disease, were readily detected. The results suggest that the Katritzky reaction combined with PSI-MS might offer a significant advance in the knowledge on protocols that improve the sensitivity of detection of crucial biological compounds.

Access to treatment for chronic kidney disease by children and adolescents in Brazil.

BACKGROUND: This study aimed to identify main factors associated with child and adolescent access to chronic kidney disease (CKD) treatment in Brazil. METHODS: Multi-center cross-sectional study conducted in eight pediatric nephrology centers across all Brazilian geographic regions. Information was collected on characteristics associated with referral and treatment of patients with CKD. The following outcomes were analyzed as follows: (1) age at first consultation, and (2) time elapsed between referral and treatment at the specialized service. RESULTS: Three hundred thirty-five children were assessed. Variables associated with age at first consultation were as follows: CAKUT (HR=1.7; 95%CI 1.3-2.2, p<0.01); private health plan (HR=1.54; 95%CI 1.06-2.23, p=0.02); modified Medical Outcomes Study Social Support Survey mMOS-SS score (HR=1.02; 95%CI 1.00-1.03, p=0.024); maternal age (HR=0.96; 95%CI 0.95-0.97, p<0.01); and number of siblings in the household (HR=0.86; 95%CI 0.79-0.83, p<0.01). Significant variables associated with time elapsed between referral and treatment at the specialized service were as follows: each additional occupant sharing the household (HR=0.94; 95%CI:0.89-0.99, p=0.02), residing in the Northeast (HR=0.81; 95%CI:0.67-0.98, p=0.03) and having someone to take them to the physician (HR=1.36; 95%CI 1.07-1.74, p=0.01). The median time interval between patient referral and treatment by the service was 11 days (IQR 10-31). CONCLUSION: There are potentially modifiable factors hampering access of children with CKD to specialized treatment. The importance of the role of social support for the two outcomes should serve as an alert for health managers and professionals to consider this aspect throughout all steps of the care process of children with CKD.

A intervenção precoce do paciente com síndrome coronariana aguda e sua implicação na redução da morbimortalidade cardiovascular / The early intervention of acute coronary disease and its implication in the reduction of cardiovascular morbimortality

Introdução. O infarto agudo do miocárdio apresenta significativas taxas de morbimortalidade. A reperfusão precoce por angioplastia primária é a intervenção que reduz a mortalidade e as complicações, e deve ser iniciada em até 12 horas, a fim de impedir a perda muscular irreversível. O tempo entre chegada do paciente ao hospital e a abertura da artéria acometida, tempo porta-balão, determina a morbimortalidade do paciente. Objetivo. Esse estudo busca analisar o potencial benefício do tratamento da reperfusão coronariana precoce, os fatores de risco, as possíveis complicações e o Killip em pacientes que sofreram infarto agudo do miocárdio relacionando-os a sua morbimortalidade. Materiais e métodos. Estudo observacional transversal realizado por meio de coleta de dados dos prontuários dos pacientes submetidos a angioplastia primária de um hospital privado. Resultados. A hipertensão arterial sistêmica foi a variável mais prevalente (75%), e que houve predomínio no sexo masculino (71%) e associação com a progressão da idade. 61% dos pacientes apresentaram um tempo porta balão menor que 90 minutos. Houve significância estatística entre o tempo porta balão e a evolução do Killip, evidenciando um tempo porta-balão maior que 90 minutos na maioria dos pacientes que obtiveram aumento da pontuação do Killip. Conclusão. A precocidade da intervenção no paciente com IAM impacta na morbimortalidade, visto que o tempo porta balão está diretamente associado a evolução da do Killip. Logo, deve-se identificar os fatores que interferem no atendimento, a fim de proporcionar uma intervenção otimizada. (AU)

Introduction. Acute myocardial infarction has significant rates of morbidity and mortality. Early reperfusion by primary angioplasty is the intervention that reduces mortality and complications, and should be started within 12 hours in order to prevent irreversible muscle loss. The time between the patient's arrival at the hospital and the opening of the affected artery, door-to-balloon time, determines the patient's morbidity and mortality. Objective. The proposition of this study is to analyze the potential benefits of early coronary reperfusion, associated with the risk factors, possible complications, and the Killip score in patients whit acute myocardial infarction (AMI) and the relation of those factors with the morbidity and mortality. Materials and methods. This is a transversal observational study and uses data collected of medical records of patients subjected to primary angioplasty in a private hospital. Results. Systemic arterial hypertension was the most prevalent one (75%), it was more common in males (71%) and associated with a higher age. In 61% of the patients port-balloon time was less than 90 minutes. There was statistical significance between port-balloon time and Killip score evaluation, that showed a higher score in patient with a port-balloon time that exceeded 90 minutes. Conclusion. Early intervention in patients with AMI impacts morbimortality, once that the port-balloon time is directly associated with the Killip score results. Therefore, all factors that can lead to a delay in their care of those patients should be identified with the objective of optimize the intervention. (AU)

Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection.

Infection of mice with Plasmodium berghei NK65 represents a well-recognized malaria model in which infection is accompanied by an intense hepatic inflammatory response. Enzyme-inducible nitric oxide synthase is an important regulator of inflammation and leukocyte recruitment in microvessels, but these functions have yet to be evaluated in experimental malaria. In this study, we assessed the involvement of inducible nitric oxide synthase in inflammatory responses to murine experimental malaria induced by P. berghei NK65. We observed that wild type (WT) and nitric oxide synthase (iNOS)-deficient mice (iNOS(-/-)) mice showed similar levels of parasitemia following P. berghei NK65 infection, although infected iNOS(-/-) mice presented early mortality. Inducible nitric oxide synthase deficiency led to increased leukocyte rolling and adhesion to the liver in iNOS(-/-) mice relative to the WT animals, as observed via intravital microscopy. Infected iNOS(-/-) mice also exhibited increased hepatic leukocyte migration and subsequent liver damage, which was associated with high serum levels of the cytokines TNF-α, IL-6 and IL-10. Our data suggest potential role for the iNOS enzyme as a regulator of hepatic inflammatory response induced by P. berghei NK65-infection, and its absence leads to exacerbated inflammation and sequential associated-hepatic damage in the animals.