Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a ‘sub-proteome’, such as the ‘metalloproteome’, defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α2macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1–1) isoform in 15% of the population.

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Relationship between serum ferritin and zinc levels in patients with major thalassemia

Paediatrica Indonesiana ◽

10.14238/pi59.3.2019.144-9 ◽

2019 ◽

Vol 59 (3) ◽

pp. 144-9

Author(s):

Hervita Yeni ◽

Finny Fitry Yani ◽

Amirah Zatil Izzah ◽

Gustina Lubis

Keyword(s):

Serum Ferritin ◽

Inductively Coupled Plasma ◽

Competitive Inhibition ◽

Serum Zinc ◽

Wilcoxon Test ◽

Control Group ◽

Healthy Controls ◽

Cross Sectional ◽

Significant Difference ◽

Zinc Levels

Background In thalassemia patients, reduced zinc absorption results from increased serum iron due to repeated blood transfusions, increased iron absorption due to ineffective erythropoiesis, and competitive inhibition between iron and zinc in binding to transferrin, a means of transporting both types of minerals in the blood. Few studies have been done to examine zinc levels in thalassemia patients and its relationship with ferritin. Objective To compare serum zinc in thalassemia patients and healthy controls and to assess for a possible correlation between serum ferritin and zinc in thalassemia patients. Methods This cross-sectional study in 68 subjects was done from October 2016 to August 2017. Serum ferritin measured by chemiluminescence immunoassay and serum zinc by inductively coupled plasma mass spectrometry (ICP-MS). Wilcoxon test was used to analyze for differences between serum zinc in thalassemia patients and controls. Spearman’s correlation test was used to analyze for a possible correlation between ferritin and serum zinc in thalassemia patients. Results There were 34 patients with thalassemia and 34 healthy control subjects. The median serum zinc was 119.34 µg/dL (IQR=71.27) in the thalassemia group and 120.08 µg/dL (IQR=26.28) in the control group (P=0.36). There was no significant correlation between serum ferritin and zinc in thalassemic children (r=-0.023; P=0.895). Conclusion There is no significant difference in serum zinc levels between thalassemic children and healthy controls. There is no significant correlation between serum ferritin and zinc in thalassemic children.

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Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

Journal of Neural Transmission ◽

10.1007/s00702-021-02374-4 ◽

2021 ◽

Author(s):

Frank Faltraco ◽

Denise Palm ◽

Adriana Uzoni ◽

Lena Borchert ◽

Frederick Simon ◽

...

Keyword(s):

Gene Expression ◽

Dermal Fibroblast ◽

Sleep Onset ◽

Dermal Fibroblasts ◽

Control Group ◽

Adhd Group ◽

Healthy Controls ◽

Circadian Gene ◽

Significant Difference ◽

Circadian Preference

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.

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Multiple sclerosis and depressive manifestations: can diffusion tensor MR imaging help in the detection of microstructural white matter changes?

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-019-0033-8 ◽

2019 ◽

Vol 50 (1) ◽

Cited By ~ 2

Author(s):

Talaat A. Hassan ◽

Shaima Fattouh Elkholy ◽

Bahaa Eldin Mahmoud ◽

Mona ElSherbiny

Keyword(s):

Multiple Sclerosis ◽

Depressive Symptoms ◽

White Matter ◽

Limbic System ◽

Diffusion Tensor ◽

Control Group ◽

Uncinate Fasciculus ◽

White Matter Tracts ◽

Significant Difference ◽

The Right

Abstract Background Multiple sclerosis is one of the commonest causes of neurological disability in middle-aged and young adults. Depression in MS patients can compromise cognitive functions, lead to suicide attempts, impair relationships and reduce compliance with disease-modifying treatments. The aim of this study was to investigate and compare the microstructural changes in the white matter tracts of the limbic system in MS patients with and those without depressive manifestations using a diffusion tensor imaging (DTI) technique. Methods This study included 40 patients who were divided into three groups. Group 1 comprised of 20 patients with relapsing-remitting MS with depressive symptoms and group 2 comprised 10 MS patients without symptoms of depression. The third group is a control group that included 10 age-matched healthy individuals. All patients underwent conventional MRI examinations and DTI to compare the fractional anisotropy (FA) values in the white matter tracts of the limbic system. Results We compared the DTI findings in MS patients with and those without depressive symptoms. It was found that patients with depression and MS exhibited a significant reduction in the FA values of the cingulum (P < 0.0111 on the right and P < 0.0142 on the left), uncinate fasciculus (P < 0.0001 on the right and P < 0.0076 on the left) and the fornix (P < 0.0001 on both sides). No significant difference was found between the FA values of the anterior thalamic radiations in both groups. Conclusion Patients with depression and MS showed more pronounced microstructural damage in the major white matter connections of the limbic pathway, namely, the uncinate fasciculus, cingulum and fornix. These changes can be detected by DTI as decreased FA values in depressed MS patients compared to those in non-depressed patients.

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Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2017-135397 ◽

2018 ◽

Vol 94 (1111) ◽

pp. 278-283 ◽

Cited By ~ 3

Author(s):

Xue-Feng Xie ◽

Xiao-Hui Huang ◽

Ai-Zong Shen ◽

Jun Li ◽

Ye-Huan Sun

Keyword(s):

Multiple Sclerosis ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Control Group ◽

Sample Type ◽

Healthy Controls ◽

Eligibility Criteria ◽

Effect Model ◽

Healthy Control

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.

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Trace elements in patients with aortic valve sclerosis

Therapeutic Advances in Cardiovascular Disease ◽

10.1177/1753944720985985 ◽

2021 ◽

Vol 15 ◽

pp. 175394472098598

Author(s):

Hataw Al-Taesh ◽

Abuzer Çelekli ◽

Murat Sucu ◽

Seyithan Taysi

Keyword(s):

Trace Elements ◽

Aortic Valve ◽

Inductively Coupled Plasma ◽

Healthy Subjects ◽

Serum Zinc ◽

Serum Levels ◽

Control Group ◽

Aortic Valve Sclerosis ◽

Inductively Coupled ◽

Significant Difference

Background: Aortic valve sclerosis (AVSc) is defined as the thickening and calcification of aortic valve cusps, in the absence of obstruction of ventricular outflow. AVSc is linked with a clear imbalance in some trace elements. Aims: The objective of this study was to investigate the relationship between AVSc and serum levels of iron (Fe), zinc (Zn), selenium (Se), and copper (Cu). Additionally, this research aimed to explore the clinical significance of human serum zinc, selenium, copper, and iron concentrations as a potential new biomarker for AVSc patients and to clarify the pathophysiological role in individuals at risk of developing AVSc. Patients and methods: The study included 40 subjects with AVSc (25% male and 75% female) who were compared with a healthy control group with the same gender ratio. AVSc was based on comprehensive echocardiographic assessments. Blood samples were taken and Zn and Cu concentrations were determined through the use of atomic absorption spectroscopy. Se was measured using an inductively coupled plasma mass spectrometry device and Fe was measured using a Beckman Coulter instrument. Results: There was a significant difference in the prevalence of diabetes, blood pressure levels, and body mass index between the patients and the healthy subjects ( p < 0.05). The differences between the serum Fe, Se, and Cu levels of the AVSc patients and the healthy subjects ( p > 0.05) were recorded. The serum Zn of AVSc patients when compared was significantly lower compared with that of the control group ( p < 0.01). Conclusion: Patients with AVSc had an imbalance in some of the trace elements in their blood. The patient group’s valves had higher serum Cu levels and lower serum Se, Zn, and Fe concentrations compared with the healthy group’s valves. In the valve patients as compared, AVSc had a high prevalence of obesity, hypertension, and diabetes.

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MO477SERUM C-REACTIVE PROTEIN AND PROCALCITONIN LEVELS IN HEMODIALYSIS AND INTRADIALYTIC ALTERATIONS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab090.0039 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Makrouhi Sonikian ◽

Aggeliki Barbatsi ◽

Eugenia Karakou ◽

Theodoros Chiras ◽

Jacob Skarakis ◽

...

Keyword(s):

Healthy Subjects ◽

Control Group ◽

Healthy Controls ◽

C Reactive Protein ◽

Polysulfone Membrane ◽

Reactive Protein ◽

Markers Of Inflammation ◽

Dialysate Flow Rate ◽

Significant Difference ◽

Serum Crp

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p<0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p<0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p<0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.

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Exploring The Clinical Significance of Serum Angiopoietin-2 In Breast Cancer Patients

QJM ◽

10.1093/qjmed/hcab091.014 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Abeer I Abd Elmagid ◽

Hala Abdel Al ◽

Wessam El Sayed Saad ◽

Seham Kamal Mohamed

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Serum Levels ◽

Tnm Staging ◽

Control Group ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Female Patients ◽

Significant Difference ◽

Angiopoietin 2

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p < 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p > 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p > 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.

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Multiple Sclerosis and Diabetes Mellitus: Further Evidence of a Relationship

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100044322 ◽

1982 ◽

Vol 9 (4) ◽

pp. 415-419 ◽

Cited By ~ 14

Author(s):

Sharon A. Warren ◽

K.G. Warren

Keyword(s):

Diabetes Mellitus ◽

Multiple Sclerosis ◽

Healthy Controls ◽

Degree Relative ◽

Significant Difference ◽

The Difference ◽

The Relationship ◽

Prevalence Of Diabetes Mellitus ◽

Second Degree

SUMMARY:One hundred multiple sclerosis (MS) patients were compared to healthy controls to determine the prevalence of diabetes mellitus in their families. Significantly, more MS patients than controls were diabetic or reported at least one first degree relative (parent, sibling, child) with diabetes. The relationship between MS and diabetes persisted when second degree relatives (grandparents, aunts and uncles) were taken into consideration.A greater percentage of MS patients with another MS relative were diabetic or reported a first degree relative with diabetes mellitus than MS patients without an MS relative. However the difference was not statistically significant. Nor was there a significant difference when percentages reporting either a first or a second degree relative with diabetes were compared.

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Cognitive effect of cilostazol in post stroke cognitive impairment: a prospective study

10.21203/rs.2.9552/v1 ◽

2019 ◽

Author(s):

Ling-Chun Huang ◽

Sun-Wung Hsieh ◽

Chun-Hung Chen ◽

Yuan-Han Yang

Keyword(s):

Ischemic Stroke ◽

Cognitive Impairment ◽

Randomized Clinical Trials ◽

Multiple Logistic Regression Analysis ◽

Antiplatelet Agent ◽

Cognitive Change ◽

Control Group ◽

Cognitive Changes ◽

Post Stroke ◽

Significant Difference

Abstract Background Whether antiplatelet agents have a preventive effect on cognitive function after ischemic stroke remains unknown. This study examined the potential effect of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, on cognitive impairment after stroke in an Asian population. Methods A total of 45 patients using cilostazol (100 mg) twice per day were enrolled as the study group and 45 patients using aspirin (100 mg) or clopidogrel (75 mg) daily were enrolled as the control group. Mini-mental state examination and Cognitive Assessment Screening Instrument were administered at the start of the study and after 6 months. Multiple logistic regression analysis was used to estimate the association between the cognitive change and cilostazol use. Results Overall, 60-70% of the patients improved their cognition after 6 months follow up. No significant differences were observed in the cognitive change between the cilostazol and control groups. However, the cilostazol group appeared to perform better in the fluency, language and judgment subdomains. Conclusions In the current study, the clinical course of post stroke cognitive changes was described. Although cilostazol did not make a significant difference in cognitive change after ischemic stroke, it may improve fluency, language and judgment subdomains. These findings should be examined further in randomized clinical trials.

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The added value of cognition-targeted exercise versus symptom-targeted exercise for multiple sclerosis fatigue: A randomized controlled pilot trial

PLoS ONE ◽

10.1371/journal.pone.0258752 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0258752

Author(s):

Azza Alketbi ◽

Salah Basit ◽

Nouran Hamza ◽

Lori M. Walton ◽

Ibrahim M. Moustafa

Keyword(s):

Multiple Sclerosis ◽

Clinical Outcome ◽

Outcome Measures ◽

Recruitment Rate ◽

Control Group ◽

Entire Study ◽

Randomized Controlled ◽

Significant Difference ◽

Intervention Protocol

Background Fatigue is considered one of the most common symptoms of multiple sclerosis (MS) and lacks a current standardized treatment. Therefore, the aim of this study was to examine the feasibility and effectiveness of a cognition-targeted exercise versus symptom-targeted exercise for MS fatigue. Methods In this Pilot, parallel-group, randomized controlled trial, sixty participants with multiple sclerosis, were randomly assigned to either a Cognition-Targeted Exercise (CTE) (N = 30, mean age 41) or a Symptom-Targeted Exercise (STE) (N = 30, mean age 42). The participants in the experimental group received eight, 50-minute sessions of weekly Cognitive Behavior Therapy (CBT) in addition to a CTE Program; whereas, participants in the control group received eight, 50-minute sessions of weekly CBT in addition to the standardized physiotherapy program (STE Program). Feasibility was assessed through recruitment rate, participant retention, adherence and safety, in addition to clinical outcome measures, including: (1) Modified Fatigue Impact Scale (MFIS), (2) Work and Social Adjustment Scale (WSAS), (3) Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS). All outcome measures were assessed at baseline (pretreatment), following completion of the eight visit intervention protocol, and at 3-months follow-up. Results The recruitment rate was 60% and 93% of participants completed the entire study. The recruited participants complied with 98% of the required visits. No adverse events were recorded. A Generalized Estimation Equation Model revealed a significant difference over time as an interaction term during the post and follow up visit for all clinical outcome measures (p < .001). Conclusion The addition of CTE to CBT exhibited positive and more lasting influence on MS fatigue outcomes compared to Symptom-Targeted Exercise (STE). Feasibility and efficacy data from this pilot study provide support for a full-scale RCT of CTE as an integral component of Multiple Sclerosis fatigue management.

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