INNV-15. PROTEIN TYPING AND MRNA ANALYSIS OF CIRCULATING EXOSOMES FOR GLIOBLASTOMA THERAPY USING PLASMONIC-ENHANCED INTEGRATED MAGNETO-ELECTROCHEMICAL SENSOR

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi108-vi108
Author(s):  
Hsing-Ying Lin ◽  
Chen-Han Huang ◽  
Peng-Wei Hsu ◽  
Yu-Jen Lu ◽  
Peter C Y Chou ◽  
...  

Abstract Monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem. Glioblastomas shed large quantities of exosomes into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Recently, we develop a highly sensitive and rapid analytical technique for profiling circulating exosomes directly from serum plasma of patients with glioblastoma. Exosomes are labeled with target-specific metal nanoparticles and detected by a miniaturized integrated magneto-electrochemical sensing system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate GBM exosomes from nontumor host cell–derived exosomes. We also show that circulating GBM exosomes can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.

2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.


2021 ◽  
pp. 112972982098317
Author(s):  
Marcello Napoli ◽  
Anna Zito ◽  
Maria Luisa Lefons ◽  
Paolo Ria ◽  
Emiliana Ferramosca ◽  
...  

Maturation failure remains a major clinical problem of distal arteriovenous fistula (AVF). Early failure (EF) is associated with the small size of the veins. For about 10 years we have used in more than 1000 fistulas, the Vessels Pre-Dilatation (VPD) to increase the recruitment of small veins for creating distal AVFs. The purpose of this study is to highlight if the VPD can reduce the incidence of EF or failure to mature (FTM) in AVFs created with small veins. Data of all the consecutive patients directly admitted to our Department for their first distal AVF from January to December 2019 were collected. The patients were divided in two groups, one with a vein diameter after the tourniquet ⩽2.0 mm (G1) and one >2 mm (G2). Both in G1 then in G2 the vessels had undergone VPD. Immediate failure (IF), EF, FTM, delayed or arrested maturation rate (DAM), unassisted AVFs and matured AFVs were evaluated. The patients recruited totalled 104, 37 in G1, and 67 in G2. The two groups were homogeneous in age, incidence of diabetes, obesity, heart disease, peripheral vasculopathy, and race. Female were more numerous in G1 (51% vs 12%, p < 0.001). In G1 and G2 occurred respectively 3 IF versus zero ( p < 0.05), 10 EF (29%) versus 6 (9%) ( p < 0.05), 6 DAM (16%) versus 6 (9%), 21 unassisted AVFs (57%) versus 57 (85%) ( p < 0.01). Dividing the patients into groups of unassisted and assisted AVFs, female and low vein diameter are more represented in the assisted group. There were 32 matured AVFs (86%) in G1 and 65 (97%) in G2. In order to increase the incidence of the distal AVF, the PDV allows to include small veins. However, more patients require further interventions to achieve maturation of the fistula.


2019 ◽  
Author(s):  
Renjie Liao ◽  
Diego Mastroeni ◽  
Paul D. Coleman ◽  
Jia Guo

AbstractThe ability to perform highly sensitive and multiplexed in situ protein analysis is crucial to advance our understanding of normal physiology and disease pathogenesis. To achieve this goal, here we develop an approach using cleavable biotin conjugated antibodies and cleavable fluorescent streptavidin (CFS). In this approach, protein targets are first recognized by the cleavable biotin labeled antibodies. Subsequently, CFS is applied to stain the protein targets. Though layer-by-layer signal amplification using cleavable biotin conjugated orthogonal antibodies and CSF, the protein detection sensitivity can be enhanced by at least 10 fold, compared with the existing methods. After imaging, the fluorophores and the biotins unbound to streptavidin are removed by chemical cleavage. The leftover streptavidin is blocked by biotin. Upon reiterative analysis cycles, a large number of different proteins with a wide range of expression levels can be unambiguously detected in individual cell in situ.


Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7185
Author(s):  
Oliver Gould ◽  
Natalia Drabińska ◽  
Norman Ratcliffe ◽  
Ben de Lacy Costello

Mass spectrometry (MS) is an analytical technique that can be used for various applications in a number of scientific areas including environmental, security, forensic science, space exploration, agri-food, and numerous others. MS is also continuing to offer new insights into the proteomic and metabolomic fields. MS techniques are frequently used for the analysis of volatile compounds (VCs). The detection of VCs from human samples has the potential to aid in the diagnosis of diseases, in monitoring drug metabolites, and in providing insight into metabolic processes. The broad usage of MS has resulted in numerous variations of the technique being developed over the years, which can be divided into hyphenated and real-time MS techniques. Hyphenated chromatographic techniques coupled with MS offer unparalleled qualitative analysis and high accuracy and sensitivity, even when analysing complex matrices (breath, urine, stool, etc.). However, these benefits are traded for a significantly longer analysis time and a greater need for sample preparation and method development. On the other hand, real-time MS techniques offer highly sensitive quantitative data. Additionally, real-time techniques can provide results in a matter of minutes or even seconds, without altering the sample in any way. However, real-time MS can only offer tentative qualitative data and suffers from molecular weight overlap in complex matrices. This review compares hyphenated and real-time MS methods and provides examples of applications for each technique for the detection of VCs from humans.


2006 ◽  
Vol 12 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Paola Albertazzi

Hot flushes are a major clinical problem for many menopausal women. Their aetiology is unknown. Centrally acting neurotransmitters are involved, but this involvement is yet to be fully characterized. In clinical trials with optimal patient selection and compliance, estrogen can reduce the frequency of hot flushes by 70–80%, and placebo by 20–40%. For some women, however, there are contraindications to the use of estrogen, and others are unwilling to use it. Furthermore, hot flushes may persist in spite of adequate estrogen replacement, and to improve symptoms physicians then have either to add another drug to the regimen or find an alternative to estrogen. The most commonly used non-hormonal alternatives for climacteric symptoms are neurotransmitter modulators such as the selective serotonin reuptake inhibitors. These reduce the frequency of hot flushes by 60%. The mechanism of this effect appears to differ from that underlying their effect on mood. They are generally well tolerated and rates of adverse events are far lower than those reported in studies of the use of these agents for depression. The limited efficacy of clonidine suggests that adrenergic mechanisms may be involved and data are awaited for more specific selective noradrenaline reuptake inhibitors. Thus, non-hormonal treatments are not as effective as estrogens in relieving hot flushes but may have a place as an alternative.


2009 ◽  
Vol 23 (4) ◽  
pp. 294-298
Author(s):  
Amit Tagare ◽  
Umesh Vaidya

Extrauterine growth retardation is a major clinical problem in preterm infants. Aggressive nutritional interventions may play an important role to fight this prevalent problem. Parenteral nutrition is almost indispensable part of aggressive nutritional approach in neonates, because of certain limitations of enteral route during first few days of life. Formidable research work done in developed world has resolved certain important issues like dosage regimens. However, still we need to resolve quite a few unanswered queries. This is especially true for Indian context where we deal with a different population of neonates than the developed world. In this article we will discuss both the resolved and unresolved issues regarding neonatal parenteral nutrition and the research priorities for us.


2021 ◽  
Vol 23 (2) ◽  
pp. 137-140
Author(s):  
Zoltán H Endre ◽  

Acute kidney injury (AKI) is a major clinical problem in the community and in hospital, with hospital-acquired AKI reported in about 20% of adult and 30% of paediatric admissions.


Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1772 ◽  
Author(s):  
Elena Lucarini ◽  
Carmen Parisio ◽  
Jacopo J. V. Branca ◽  
Cristina Segnani ◽  
Chiara Ippolito ◽  
...  

The management of visceral pain is a major clinical problem in patients affected by gastrointestinal disorders. The poor knowledge about pain chronicization mechanisms prompted us to study the functional and morphological alterations of the gut and nervous system in the animal model of persistent visceral pain caused by 2,4-dinitrobenzenesulfonic acid (DNBS). This agent, injected intrarectally, induced a colonic inflammation peaking on day 3 and remitting progressively from day 7. In concomitance with bowel inflammation, the animals developed visceral hypersensitivity, which persisted after colitis remission for up to three months. On day 14, the administration of pain-relieving drugs (injected intraperitoneally and intrathecally) revealed a mixed nociceptive, inflammatory and neuropathic pain originating from both the peripheral and central nervous system. At this time point, the colonic histological analysis highlighted a partial restitution of the tunica mucosa, transmural collagen deposition, infiltration of mast cells and eosinophils, and upregulation of substance P (SP)-positive nerve fibers, which were surrounded by eosinophils and MHC-II-positive macrophages. A significant activation of microglia and astrocytes was observed in the dorsal and ventral horns of spinal cord. These results suggest that the persistence of visceral pain induced by colitis results from maladaptive plasticity of the enteric, peripheral and central nervous systems.


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