scholarly journals The Synthesis of Carbohydrate Probes for the Diagnosis of Multiple Sclerosis

2021 ◽  
Author(s):  
◽  
Kristiana Santoso

<p>Multiple sclerosis (MS) is a neurologically debilitating disease which typically affects people in the age bracket of 27-40 years old. Currently, little is known about the mechanism of the disease, which is partly due to the lack of a reliable diagnostic test. There are two common ways of diagnosing MS, neither of which are specific to MS. One is the detection of IgG antibodies in the cerebrospinal fluid (CSF), a painful and invasive test, and the other involves obtaining MRIs of the brain to locate and monitor plaques in brain, which can be expensive and harmful. Early detection of the disease could not only lead to better symptom management, but would also allow for better monitoring of disease progress and, accordingly, lead to a better understanding of MS pathology. To this end, a reliable and non-invasive diagnostic test for the early detection of MS is required.  In 2006, it was reported that antibodies against α-Glc and α-Glc(α-1,4)Glc were found at elevated levels in the sera of MS patients when compared to healthy patients’ sera, and it has been proposed that the presence of these two carbohydrates in patient serum might serve as a way to detect the onset and prognosis of MS. Accordingly, this Masters project sought to explore this hypothesis via the synthesis of α-Glc and α-Glc(α-1,4)Glc, both glycosides and glycodendrons, which could then be used to potentially detect MS-specific antibodies in sera. To this end, both glycans were prepared and coupled to biotin, ready to be used to bind streptavidin-coated enzyme-linked immunosorbent assay (ELISA) plates. An ELISA protocol is to be established by the optimisation of the negative control in order to test such glycans against plasma samples. In the hope to achieve a multivalent system, a dendrimeric scaffold was also prepared that can be used to prepare larger glycan structures for the immunodiffusion assay. Ultimately, this could lead to a new diagnostic test for MS.</p>

2021 ◽  
Author(s):  
◽  
Kristiana Santoso

<p>Multiple sclerosis (MS) is a neurologically debilitating disease which typically affects people in the age bracket of 27-40 years old. Currently, little is known about the mechanism of the disease, which is partly due to the lack of a reliable diagnostic test. There are two common ways of diagnosing MS, neither of which are specific to MS. One is the detection of IgG antibodies in the cerebrospinal fluid (CSF), a painful and invasive test, and the other involves obtaining MRIs of the brain to locate and monitor plaques in brain, which can be expensive and harmful. Early detection of the disease could not only lead to better symptom management, but would also allow for better monitoring of disease progress and, accordingly, lead to a better understanding of MS pathology. To this end, a reliable and non-invasive diagnostic test for the early detection of MS is required.  In 2006, it was reported that antibodies against α-Glc and α-Glc(α-1,4)Glc were found at elevated levels in the sera of MS patients when compared to healthy patients’ sera, and it has been proposed that the presence of these two carbohydrates in patient serum might serve as a way to detect the onset and prognosis of MS. Accordingly, this Masters project sought to explore this hypothesis via the synthesis of α-Glc and α-Glc(α-1,4)Glc, both glycosides and glycodendrons, which could then be used to potentially detect MS-specific antibodies in sera. To this end, both glycans were prepared and coupled to biotin, ready to be used to bind streptavidin-coated enzyme-linked immunosorbent assay (ELISA) plates. An ELISA protocol is to be established by the optimisation of the negative control in order to test such glycans against plasma samples. In the hope to achieve a multivalent system, a dendrimeric scaffold was also prepared that can be used to prepare larger glycan structures for the immunodiffusion assay. Ultimately, this could lead to a new diagnostic test for MS.</p>


2020 ◽  
Vol 16 (5) ◽  
pp. 557-569 ◽  
Author(s):  
Maryam Kharati ◽  
Sanam Foroutanparsa ◽  
Mohammad Rabiee ◽  
Reza Salarian ◽  
Navid Rabiee ◽  
...  

Background: Multiple Sclerosis (MS) involves an immune-mediated response in which body’s immune system destructs the protective sheath (myelin). Part of the known MS biomarkers are discovered in cerebrospinal fluid like oligoclonal lgG (OCGB), and also in blood like myelin Oligodendrocyte Glycoprotein (MOG). The conventional MS diagnostic methods often fail to detect the disease in early stages such as Clinically Isolated Syndrome (CIS), which considered as a concerning issue since CIS highlighted as a prognostic factor of MS development in most cases. Methods: MS diagnostic techniques include Magnetic Resonance Imaging (MRI) of the brain and spinal cord, lumbar puncture (or spinal tap) that evaluate cerebrospinal fluid, evoked potential testing revealing abnormalities in the brain and spinal cord. These conventional diagnostic methods have some negative points such as extensive processing time as well as restriction in the quantity of samples that can be analyzed concurrently. Scientists have focused on developing the detection methods especially early detection which belongs to ultra-sensitive, non-invasive and needed for the Point of Care (POC) diagnosis because the situation was complicated by false positive or negative results. Results: As a result, biosensors are utilized and investigated since they could be ultra-sensitive to specific compounds, cost effective devices, body-friendly and easy to implement. In addition, it has been proved that the biosensors on physiological fluids (blood, serum, urine, saliva, milk etc.) have quick response in a non-invasive rout. In general form, a biosensor system for diagnosis and early detection process usually involves; biomarker (target molecule), bio receptor (recognition element) and compatible bio transducer. Conclusion: Studies underlined that early treatment of patients with high possibility of MS can be advantageous by postponing further abnormalities on MRI and subsequent attacks. : This Review highlights variable disease diagnosis approaches such as Surface Plasmon Resonance (SPR), electrochemical biosensors, Microarrays and microbeads based Microarrays, which are considered as promising methods for detection and early detection of MS.


2013 ◽  
Vol 9 (1) ◽  
Author(s):  
Henning Hanken ◽  
Juliane Kraatz ◽  
Ralf Smeets ◽  
Max Heiland ◽  
Marco Blessmann ◽  
...  

Abstract Objective The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope® using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions. Materials and methods 120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope®. Biopsies were obtained from all suspicious areas identified in both examination groups (n = 52). The diagnostic strategies were compared regarding sensitivity and specificity. Results Based upon the result, use of the VELscope® leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope® is inferior (8.4%). Conclusion The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e020476 ◽  
Author(s):  
Manuel Romero-Saldaña ◽  
Pedro Tauler ◽  
Manuel Vaquero-Abellán ◽  
Angel-Arturo López-González ◽  
Francisco-José Fuentes-Jiménez ◽  
...  

ObjectivesA non-invasive method for the early detection of metabolic syndrome (NIM-MetS) using only waist-to-height ratio (WHtR) and blood pressure (BP) has recently been published, with fixed cut-off values for gender and age. The aim of this study was to validate this method in a large sample of Spanish workers.DesignA diagnostic test accuracy to assess the validity of the method was performed.SettingOccupational health services.ParticipantsThe studies were conducted in 2012–2016 on a sample of 60 799 workers from the Balearic Islands (Spain).InterventionsThe NCEP-ATP III criteria were used as the gold standard. NIM-MetS has been devised using classification trees (the χ2automatic interaction detection method).Main outcome measuresAnthropometric and biochemical variables to diagnose MetS. Sensitivity, specificity, validity index and Youden Index were determined to analyse the accuracy of the diagnostic test (NIM-MetS).ResultsWith regard to the validation of the method, sensitivity was 54.7%, specificity 94.9% and the Validity Index 91.2%. The cut-off value for WHtR was 0.54, ranging from 0.51 (lower age group) to 0.56 (higher age group). Variables more closely associated with MetS were WHtR (area under the curve (AUC)=0.85; 95% CI 0.84 to 0.86) and systolic BP (AUC=0.79; 95% CI 0.78 to 0.80)). The final cut-off values for the non-invasive method were WHtR ≥0.56 and BP ≥128/80 mm Hg, which includes four levels of MetS risk (very low, low, moderate and high).ConclusionsThe analysed method has shown a high validity index (higher than 91%) for the early detection of MetS. It is a non-invasive method that is easy to apply and interpret in any healthcare setting. This method provides a scale of MetS risk which allows more accurate detection and more effective intervention.


Author(s):  
Zhaoyue Shi ◽  
Khue Tran ◽  
Christof Karmonik ◽  
Timothy Boone ◽  
Rose Khavari

Abstract Background Several studies have reported brain activations and functional connectivity (FC) during micturition using functional magnetic resonance imaging (fMRI) and concurrent urodynamics (UDS) testing. However, due to the invasive nature of UDS procedure, non-invasive resting-state fMRI is being explored as a potential alternative. The purpose of this study is to evaluate the feasibility of utilizing resting states as a non-invasive alternative for investigating the bladder-related networks in the brain. Methods We quantitatively compared FC in brain regions belonging to the bladder-related network during the following states: ‘strong desire to void’, ‘voiding initiation (or attempt at voiding initiation)’, and ‘voiding (or continued attempt of voiding)’ with FC during rest in nine multiple sclerosis women with voiding dysfunction using fMRI data acquired at 7 T and 3 T. Results The inter-subject correlation analysis showed that voiding (or continued attempt of voiding) is achieved through similar network connections in all subjects. The task-based bladder-related network closely resembles the resting-state intrinsic network only during voiding (or continued attempt of voiding) process but not at other states. Conclusion Resting states fMRI can be potentially utilized to accurately reflect the voiding (or continued attempt of voiding) network. Concurrent UDS testing is still necessary for studying the effects of strong desire to void and initiation of voiding (or attempt at initiation of voiding).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melike Kurt ◽  
Zeki Yumuk

AbstractThe colorectal cancer is a serious health problem. The diagnosis of the disease mostly relies on an invasive procedure. A non-invasive diagnostic test such as an immunoassay, may facilitate diagnosis of colorectal cancer. The purpose of the study was to evaluate the use of antibodies against Fusobacterium nucleatum in the diagnosis of colorectal cancer (CRC). Totally 78 patients in three groups were included in the study. F. nucleatum in the tissues was detected using quantitative polymerase chain reaction assay. F. nucleatum IgA and IgG were measured using enzyme linked immunosorbent assay. F. nucleatum was detected in 86.7% and 73.1% cases of CRC and precancerous-benign colon disease (P-BCD), respectively. The OD values from F. nucleatum IgA and IgG ELISA tests were higher in CRC group compared with healthy individuals. The sensitivity of IgA ELISA test varied between 31.8 and 95.5% depending on the chosen cut-off values. The positivity rate of antibodies in patients with high amount of F. nucleatum in tissue was significantly greater than in the negative group. The F. nucleatum IgA and IgG antibodies in CRC were higher than the ones in healthy controls but the discriminative ability of the ELISA test was not adequate to be considered as a diagnostic tool.


Author(s):  
Pierre Nsele Mutantu ◽  
Mya Myat Ngwe Tun ◽  
Takeshi Nabeshima ◽  
Fuxun Yu ◽  
Patrick Kakoni Mukadi ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Real-time RT-PCR is the most commonly used method for COVID-19 diagnosis. However, serological assays are urgently needed as complementary tools to RT-PCR. Hachim et al. 2020 and Burbelo et al. 2020 demonstrated that anti-nucleocapsid(N) SARS-CoV-2 antibodies are higher and appear earlier than the spike antibodies. Additionally, cross-reactive antibodies against N protein are more prevalent than those against spike protein. We developed a less cross-reactive immunoglobulin G (IgG) indirect ELISA by using a truncated recombinant SARS-CoV-2 N protein as assay antigen. A highly conserved region of coronaviruses N protein was deleted and the protein was prepared using an E. coli protein expression system. A total of 177 samples collected from COVID-19 suspected cases and 155 negative control sera collected during the pre-COVID-19 period were applied to evaluate the assay’s performance, with the plaque reduction neutralization test and the commercial SARS-CoV-2 spike protein IgG ELISA as gold standards. The SARS-CoV-2 N truncated protein-based ELISA showed similar sensitivity (91.1% vs. 91.9%) and specificity (93.8% vs. 93.8%) between the PRNT and spike IgG ELISA, as well as also higher specificity compared to the full-length N protein (93.8% vs. 89.9%). Our ELISA can be used for the diagnosis and surveillance of COVID-19.


2017 ◽  
Vol 11 (08) ◽  
pp. 662-667
Author(s):  
Tatjana Vilibic-Cavlek ◽  
Ljiljana Betica-Radic ◽  
Giulietta Venturi ◽  
Claudia Fortuna ◽  
Stjepan Djuricic ◽  
...  

In the last few years, several imported cases of Zika virus (ZIKV) infection were reported in European countries. We report the first imported ZIKV infection case in a Croatian traveler returning from Brazil. The patient presented with a low-grade fever, pruritic rash, general weakness, myalgia, arthralgia and edema of the legs and recovered completely within a week. ZIKV infection was confirmed by detection of IgM/IgG antibodies using enzyme-linked immunosorbent assay (ELISA) and confirmed by plaque-reduction neutralization test (PRNT). ZIKV IgM antibodies cross-reacted with dengue virus (DENV), West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) in ELISA. In indirect immunofluorescence assay (IFA), IgM cross-reactivity was found only with DENV-3.  ZIKV IgG antibodies cross-reacted with DENV in both ELISA and IFA. PRNT for DENV was negative. Control serology performed on days 64 and 98 after disease onset showed a decline in cross-reactive heterologous DENV IgG antibodies compared to persistently high titer of homologous ZIKV IgG antibodies.


2014 ◽  
Vol 20 (11) ◽  
pp. 1425-1431 ◽  
Author(s):  
Andreia N Carvalho ◽  
Jamie L Lim ◽  
Philip G Nijland ◽  
Maarten E Witte ◽  
Jack Van Horssen

Oxidative stress has been strongly implicated in both the inflammatory and neurodegenerative pathological mechanisms in multiple sclerosis (MS). In response to oxidative stress, cells increase and activate their cellular antioxidant mechanisms. Glutathione (GSH) is the major antioxidant in the brain, and as such plays a pivotal role in the detoxification of reactive oxidants. Previous research has shown that GSH homeostasis is altered in MS. In this review, we provide a comprehensive overview on GSH metabolism in brain cells, with a focus on its involvement in MS. The potential of GSH as an in vivo biomarker in MS is discussed, along with a short overview of improvements in imaging methods that allow non-invasive quantification of GSH in the brain. These methods might be instrumental in providing real-time measures of GSH, allowing the assessment of the oxidative state in MS patients and the monitoring of disease progression. Finally, the therapeutic potential of GSH in MS is discussed.


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