Novel urinary markers: taurine, dopamine and L-fucose levels in predicting neonatal seizures

Introduction and Aim: Neonatal seizure is an age specific neurological emergency. Their unique pathophysiological mechanism has become subject of interest for many research studies. The recurrence risk for seizures is high during neonatal period and currently used treatment strategies have limited efficacy in preventing it. From past decades although the treatment has not changed, there is a gradual progress in various mechanisms that are involved in generation of seizures and their response to anti-epileptics. With the emergence of new biochemical parameters for risk assessment in patients with seizures, there is a strong need for their comparative evaluation in order to evaluate their potential clinical application. So, this study was carried out to compare the urine levels of taurine, dopamine and fucose in assessing their role in mechanism of seizure. Materials and Methods: After obtaining ethical approval and consent from parents total 43 neonates, urine taurine, dopamine and fucose were measured in 24 cases of seizures and 19 apparently healthy normal controls. Dopamine and Taurine were measured using ELISA and L-fucose by Dische and Shettles method. Results: The median level of urine fucose was significantly higher in male neonates, taurine was significantly decreased in cases compared to that of controls. Males had higher preponderance to develop seizures. The median levels of urine dopamine were high in cases compared to controls but has not showed any significance. Conclusion: Amino acid like taurine, carbohydrate moiety like fucose and a neuromodulator like dopamine may have a mechanistic role in development of seizures in neonatal period.

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Humoral Immunity in Heart Failure

Cardiovascular & Haematological Disorders - Drug Targets ◽

10.2174/1871529x18666180518101527 ◽

2019 ◽

Vol 19 (1) ◽

pp. 14-18 ◽

Cited By ~ 2

Author(s):

Amrita Sarkar ◽

Khadija Rafiq

Keyword(s):

Heart Failure ◽

Humoral Immunity ◽

Treatment Strategies ◽

Pathophysiological Mechanism ◽

Peripheral Vascular ◽

Cardiac Inflammation ◽

Humoral Immune ◽

Humoral Immune System ◽

New Treatment ◽

Immunity Function

Cardiovascular Disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to Heart Failure (HF). There are several treatments available all over the world, but still, CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is a major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play a specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential and may suggest potential new treatment strategies.

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Genetic Neonatal-Onset Epilepsies and Developmental/Epileptic Encephalopathies with Movement Disorders: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms22084202 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4202

Author(s):

Carlotta Spagnoli ◽

Carlo Fusco ◽

Antonio Percesepe ◽

Vincenzo Leuzzi ◽

Francesco Pisani

Keyword(s):

Movement Disorders ◽

Time Course ◽

Neonatal Period ◽

Age Of Onset ◽

Brain Mri ◽

Neonatal Seizure ◽

Mri Findings ◽

Epileptic Encephalopathies ◽

Pathogenic Variants ◽

Neonatal Onset

Despite expanding next generation sequencing technologies and increasing clinical interest into complex neurologic phenotypes associating epilepsies and developmental/epileptic encephalopathies (DE/EE) with movement disorders (MD), these monogenic conditions have been less extensively investigated in the neonatal period compared to infancy. We reviewed the medical literature in the study period 2000–2020 to report on monogenic conditions characterized by neonatal onset epilepsy and/or DE/EE and development of an MD, and described their electroclinical, genetic and neuroimaging spectra. In accordance with a PRISMA statement, we created a data collection sheet and a protocol specifying inclusion and exclusion criteria. A total of 28 different genes (from 49 papers) leading to neonatal-onset DE/EE with multiple seizure types, mainly featuring tonic and myoclonic, but also focal motor seizures and a hyperkinetic MD in 89% of conditions, with neonatal onset in 22%, were identified. Neonatal seizure semiology, or MD age of onset, were not always available. The rate of hypokinetic MD was low, and was described from the neonatal period only, with WW domain containing oxidoreductase (WWOX) pathogenic variants. The outcome is characterized by high rates of associated neurodevelopmental disorders and microcephaly. Brain MRI findings are either normal or nonspecific in most conditions, but serial imaging can be necessary in order to detect progressive abnormalities. We found high genetic heterogeneity and low numbers of described patients. Neurological phenotypes are complex, reflecting the involvement of genes necessary for early brain development. Future studies should focus on accurate neonatal epileptic phenotyping, and detailed description of semiology and time-course, of the associated MD, especially for the rarest conditions.

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Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.191 ◽

2010 ◽

Vol 31 (1) ◽

pp. 17-35 ◽

Cited By ~ 422

Author(s):

Martin Lauritzen ◽

Jens Peter Dreier ◽

Martin Fabricius ◽

Jed A Hartings ◽

Rudolf Graf ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurological Disorders ◽

Cortical Spreading Depression ◽

Spreading Depression ◽

Neuronal Damage ◽

Ion Homeostasis ◽

Large Body ◽

Treatment Strategies ◽

Pathophysiological Mechanism

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

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Catatonia Associated With Late Paraphrenia Successfully Treated With Lithium: A Case Report

10.21203/rs.3.rs-107295/v1 ◽

2020 ◽

Author(s):

Hiroko Sugawara ◽

Junpei Takamatsu ◽

Mamoru Hashimoto ◽

Manabu Ikeda

Keyword(s):

Case Report ◽

Mood Disorders ◽

Electroconvulsive Therapy ◽

Late Onset ◽

Treatment Strategies ◽

Psychotic Symptoms ◽

Case Presentation ◽

Limited Efficacy ◽

Cumulative Evidence ◽

The Brain

Abstract Background: Catatonia is a psychomotor syndrome that presents various symptoms ranging from stupor to agitation, with prominent disturbances of volition. Its pathogenesis is poorly understood. Benzodiazepines and electroconvulsive therapy (ECT) are safe and effective standard treatments for catatonia; however, alternative treatment strategies have not been established in cases where these treatments are either ineffective or unavailable. Here, we report a case of catatonia associated with late paraphrenia classified as very-late-onset schizophrenia-like psychosis, which was successfully treated with lithium. Case presentation: A 66-year-old single man with hearing impairment developed hallucination and delusions and presented with catatonic stupor after a fall. He initially responded to benzodiazepine therapy; however, his psychotic symptoms became clinically evident and benzodiazepine provided limited efficacy. Blonanserin was ineffective, and ECT was unavailable. His catatonic and psychotic symptoms were finally relieved by lithium monotherapy.Conclusions: Catatonic symptoms are common in patients with mood disorders, suggesting that lithium may be effective in these cases. Moreover, lithium may be effective for both catatonic and psychotic symptoms, as it normalizes imbalances of excitatory and inhibitory systems in the brain, which underlies major psychosis. Cumulative evidence from further cases is needed to validate our findings.

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Neonatal Antiepileptic Medication Treatment Patterns: A Decade of Change

American Journal of Perinatology ◽

10.1055/s-0039-1698457 ◽

2019 ◽

Author(s):

Vi T. Le ◽

Hibo H. Abdi ◽

Pablo J. Sánchez ◽

Lina Yossef ◽

Patricia B. Reagan ◽

...

Keyword(s):

Neonatal Period ◽

Health Information System ◽

Neonatal Seizure ◽

Long Term Outcomes ◽

Adjusted Risk ◽

Antiepileptic Medication ◽

Anticonvulsant Medication ◽

Risk Ratios ◽

Ischemic Encephalopathy

Abstract Objective This article aims to describe the frequency and characteristics of anticonvulsant medication treatments initiated in the neonatal period. Study Design We analyzed a cohort of neonates with a seizure diagnosis who were discharged from institutions in the Pediatric Health Information System between 2007 and 2016. Adjusted risk ratios and 95% confidence intervals for characteristics associated with neonatal (≤ 28 days postnatal) anticonvulsant initiation were calculated via modified Poisson regression. Results A total of 6,245 infants from 47 institutions were included. There was a decrease in both phenobarbital initiation within the neonatal period (96.9 to 91.3%, p = 0.015) and continuation at discharge (90.6 to 68.6%, p <0.001). Levetiracetam (7.9 to 39.6%, p < 0.001) initiation within the neonatal period and continuation at discharge (9.4 to 49.8%, p < 0.001) increased. Neonates born at ≥ 37 weeks' gestation and those diagnosed with intraventricular hemorrhage, ischemic/thrombotic stroke, other hemorrhagic stroke, and hypoxic ischemic encephalopathy (HIE) had a higher probability of anticonvulsant administration. The most prevalent diagnosis was HIE (n = 2,223, 44.4%). Conclusion Phenobarbital remains the most widely used neonatal seizure treatment. Levetiracetam is increasingly used as a second line therapy. Increasing levetiracetam use indicates a need for additional study to determine its effectiveness in reducing seizure burden and improving long-term outcomes.

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Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up

Cancers ◽

10.3390/cancers12123624 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3624

Author(s):

Abdul K. Siraj ◽

Sandeep Kumar Parvathareddy ◽

Zeeshan Qadri ◽

Khawar Siddiqui ◽

Saif S. Al-Sobhi ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Hazard Rate ◽

Tumor Recurrence ◽

Cox Regression ◽

Middle Eastern ◽

Treatment Strategies ◽

Recurrence Risk ◽

Papillary Thyroid ◽

Cox Regression Analysis

Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

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Exogenous Application of Proteoglycan to the Cell Surface Microenvironment Facilitates to Chondrogenic Differentiation and Maintenance

International Journal of Molecular Sciences ◽

10.3390/ijms21207744 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7744

Author(s):

Teruaki Masutani ◽

Shuhei Yamada ◽

Akira Hara ◽

Tatsuji Takahashi ◽

Paul G Green ◽

...

Keyword(s):

Cell Surface ◽

Tyrosine Kinases ◽

Endochondral Ossification ◽

Three Dimensional ◽

Treatment Strategies ◽

Dimensional Structure ◽

Pathophysiological Mechanism ◽

Nasal Cartilage ◽

Chondroprogenitor Cells ◽

Extracellular Matrix Components

Osteoarthritis (OA), a disease that greatly impacts quality of life, has increasing worldwide prevalence as the population ages. However, its pathogenic mechanisms have not been fully elucidated and current therapeutic treatment strategies are inadequate. In recent years, abnormal endochondral ossification in articular cartilage has received attention as a pathophysiological mechanism in OA. Cartilage is composed of abundant extracellular matrix components, which are involved in tissue maintenance and regeneration, but how these factors affect endochondral ossification is not clear. Here, we show that the application of aggrecan-type proteoglycan from salmon nasal cartilage (sPG) exhibited marked proliferative capacity through receptor tyrosine kinases in chondroprogenitor cells, and also exhibited differentiation and three-dimensional structure formation via phosphorylation of Insulin-like Growth Factor-1 Receptor and Growth Differentiation Factor 5 expression. Furthermore, sPG inhibited calcification via expression of Runx2 and Col10 (factors related to induction of calcification), while increasing Mgp, a mineralization inhibitory factor. As a result of analyzing the localization of sPG applied to the cells, it was localized on the surface of the cell membrane. In this study, we found that sPG, as a biomaterial, could regulate cell proliferation, differentiation and calcification inhibition by acting on the cell surface microenvironment. Therefore, sPG may be the foundation for a novel therapeutic approach for cartilage maintenance and for improved symptoms in OA.

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Predicting Venous Thromboembolism Recurrence Risk in Patients with Cancer: A Validation Study

Blood ◽

10.1182/blood.v120.21.394.394 ◽

2012 ◽

Vol 120 (21) ◽

pp. 394-394

Author(s):

Martha L Louzada ◽

Gauruv Bose ◽

Andrew Cheung ◽

Benjamin H Chin-Yee ◽

Simon Wells ◽

...

Keyword(s):

High Risk ◽

Low Molecular Weight Heparin ◽

Treatment Strategies ◽

Prediction Rule ◽

Clinical Prediction Rule ◽

Recurrence Risk ◽

Low Molecular Weight ◽

Clinical Prediction ◽

Unusual Site ◽

Patients With Cancer

Abstract Abstract 394 Background: Long-term low molecular weight heparin (LMWH) is the current standard for treatment of venous thromboembolism (VTE) in cancer patients. Whether treatment strategies should vary according to individual risk of VTE recurrence remains unknown. We have derived a clinical prediction rule that stratifies VTE recurrence risk in patients with cancer-associated VTE. The derivation model includes 4 independent predictors (sex, primary tumor site, stage and prior VTE). The score sum ranges between −3 and +3 points. Patients with a score ≤ 0 had low risk (≤4.5%) for recurrence and patients with a score above 1 had a high risk (≥ 19%) for VTE recurrence. Subsequently, we applied and validated the rule in an independent set of 819 patients from 2 randomized controlled trials comparing LMWH to warfarin for VTE treatment in cancer patients. In the current study we aim to externally validate our clinical prediction rule with an independent population of patients with cancer-associated VTE followed at the Thrombosis clinics of two tertiary Canadian centres. Methods: We conducted a retrospective cohort study of patients with cancer and VTE diagnosed and/or followed at the Thrombosis Clinic of the Victoria Hospital (London, Canada) from January 2006 to December 2010; and the Thrombosis Unit of the Ottawa Hospital (Ottawa, Canada) from January 2009 to December 2011. We included data from adult patients with active malignancy and objectively diagnosed acute pulmonary embolism (PE) or deep venous thrombosis (DVT) of the lower extremity (above knee), upper extremity and neck veins, or unusual site thrombosis. The primary outcome measure was VTE recurrence during the first six months of anticoagulation. Results: 353 patients fulfilled our inclusion criteria and were included in the study. There were 149 males, and the overall population had a median age of 64 years (range: 18 – 95). One hundred and twenty-three patients had lower extremity DVT, 93 had PE and 57 had both. The remaining 80 patients had either upper extremity/neck DVT (n = 55) or unusual site thrombosis (n = 25). 77 patients had a prior history of VTE. The most common primary tumour site was gastrointestinal, followed by the lung. Of the 304 patients with solid tumours, 230 (75.7%%) had TNM greater than I. Two hundred and ninety-three (83.0%) patients were treated with longterm low molecular weight heparin (LMWH) only and 60 (17.0%) with warfarin (VKA). VTE recurrence occurred in 44 of 353 patients (12.4%). When we evaluated VTE recurrence risk per site, there was no significant difference: London 13 of 90 and Ottawa 31 of 263 [RR=1.23 (95%CI= 0.671 – 2.237; p=0. 507)]. In addition, there was no significant benefit with the use of LMWH (37 of 293) over VKA (7 of 60) in the risk of recurrence [RR=0.92 (95%CI= 0.433 – 1.973; p= 0.8379)]. When we applied our clinical prediction rule (Table 1) in the entire study population, recurrent VTE occurred in 12 of 204 (5.8%) patients stratified as low risk probability and in 32 of 149 (21.4%) patients stratified as high risk probability (Table 2). Conclusions: Our prediction rule has been adequately validated to now be used in prospective trials of treatment. Future trials evaluating novel treatment strategies for high risk patients are warranted. Disclosures: No relevant conflicts of interest to declare.

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Feasibility study of a randomised controlled trial to investigate the treatment of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study protocol

BMJ Open ◽

10.1136/bmjopen-2017-018532 ◽

2017 ◽

Vol 7 (12) ◽

pp. e018532 ◽

Cited By ~ 1

Author(s):

Christopher Atkins ◽

Richard Fordham ◽

Allan B Clark ◽

Andrea Stockl ◽

Andrew P Jones ◽

...

Keyword(s):

Controlled Trial ◽

Treatment Strategies ◽

Poor Response ◽

Primary Objective ◽

University Hospital ◽

Feasibility Trial ◽

Central Research ◽

Ethical Approval ◽

Randomised Controlled ◽

Treatment Of Sarcoidosis

IntroductionFatigue is a frequent and troublesome manifestation of chronic sarcoidosis. This symptom can be debilitating and difficult to treat, with poor response to the treatment. Symptomatic management with neurostimulants, such as methylphenidate, is a possible treatment option. The use of such treatment strategies is not without precedent and has been trialled in cancer-related fatigue. Their use in sarcoidosis requires further evaluation before it can be recommended for clinical practice.Methods and analysisThe Fatigue and Sarcoidosis—Treatment with Methylphenidate study is a randomised, controlled, parallel-arm and feasibility trial of methylphenidate for the treatment of sarcoidosis-associated fatigue. Patients are eligible if they have a diagnosis of sarcoidosis, significant fatigue (measured using the Fatigue Assessment Scale) and have stable disease. Up to 30 participants will be randomly assigned to either methylphenidate (20 mg two times per day) or identical placebo in a 3:2 ratio for 24 weeks. The primary objective is to collect data determining the feasibility of a future study powered to determine the clinical efficacy of methylphenidate for sarcoidosis-associated fatigue. The trial is presently open and will continue until July 2018.Ethics and disseminationEthical approval for the study was granted by the Cambridge Central Research Ethics Committee on 21 June 2016 (reference 16/EE/0087) and was approved and sponsored by the Norfolk and Norwich University Hospital (reference 190280). Clinical Trial Authorisation (EudraCT number 2016-000342-60) from the Medicines and Healthcare products Regulatory Agency (MHRA) was granted on 19 April 2016. Results will be presented at relevant conferences and submitted to appropriate journals following trial closure and analysis.Trial registration numberNCT02643732; Pre-results.

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FoxP3− Tr1 Cell in Generalized Myasthenia Gravis and Its Relationship With the Anti-AChR Antibody and Immunomodulatory Cytokines

Frontiers in Neurology ◽

10.3389/fneur.2021.755356 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huanyu Meng ◽

Shuyu Zheng ◽

Qinming Zhou ◽

Yining Gao ◽

You Ni ◽

...

Keyword(s):

T Cell ◽

Myasthenia Gravis ◽

Treg Cells ◽

Pathophysiological Mechanism ◽

Cell Ratio ◽

Positive Correlation ◽

And Function ◽

The Relationship ◽

Normal Controls ◽

Tr1 Cells

Introduction: The changes in the number and function of regulatory T cells (Tregs) are thought to play important roles in the pathogenesis of generalized myasthenia gravis (gMG). Previous studies have suggested the decrease of FoxP3+ Treg cells in the MG development. However, there is no study on the pathophysiological mechanism of FoxP3−Treg, especially Tr1 cells, in gMG patients. Therefore, this study was conducted to reveal the effect of Tr1 cells to the pathophysiology of gMG.Methods: Thirteen patients with gMG and twelve healthy volunteers were enrolled in this study. The titer of anti-AChR Ab was measured by ELISA. The separated PBMCs were labeled for CD4, CD25, CD49b, LAG3 and FoxP3. The CD4+ T cell count, FoxP3+ Treg to CD4+ T cell ratio and Tr1 cell to CD4+ T cell ratio were measured by flow cytometry. Based on the FoxP3+ Treg and Tr1 cell to CD4+ T cell ratios, the patients' Tr1 cell to FoxP3+ Treg ratios were calculated. The IL-6, IL-7, IL-10, TGF-β and IFN-γ concentration in the serum of MG patients and normal controls (NCs) were measured via ELISA.Results: We found a significantly positive correlation between the Tr1 cell/CD4+ T cell ratio and the anti-AChR Ab (r = 0.6889 ± 0.4414, p = 0.0401). Although there were no significant differences in the relationship between FoxP3+ Treg cells and anti-AChR Ab, a positive correlation between the Tr1 cell/FoxP3+ Treg cell ratio and the anti-AChR Ab (r = 0.7110 ± 0.4227, p = 0.0318) was observed. In addition, the Tr1 cell/CD4+ T cell ratio but not the proportion of FoxP3+ Tregs was positively correlated with IL-10 (p = 0.048). These results suggested that in the process of the immunomodulatory effect of Tr1 cells in patients with gMG, IL-10 and other cytokines may be involved, but the specific mechanism needs further study.Conclusion: This is the first study of the immunoregulatory mechanism of Tr1 cells in gMG. We conducted this study to elucidate the significance of Tr1 cells in the pathogenesis of MG. We believe that in patients with gMG, Tr1 cells may play an immunomodulatory role in counteracting AChR-related autoimmune responses. In this process, IL-10 and other immunomodulatory cytokines may be involved.

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