scholarly journals A Randomized, Triple-blind Placebo-controlled Trial to Determine the Effect of Saffron on the Serum Levels of MMP-9 and TIMP-1 in Patients with Multiple Sclerosis

Author(s):  
Fatemeh Ghasemi Sakha ◽  
Amirreza Azimi Saeen ◽  
Seyed Mohammad Moazzeni ◽  
Farnaz Etesam ◽  
Gholamhassan Vaezi

Matrix metalloproteinases-(MMP)-9 facilitates the migration of T-cells to central nervous system (CNS), while (Tissue inhibitor of metalloproteinases-1) TIMP-1 inhibits the function of MMP-9. This study aimed to determine the appropriate treatment option for multiple sclerosis (MS). Forty-three relapsing-remitting MS (RRMS) patients were randomly divided into two groups of 22 (group A, placebo) and 21 (group B, Saffron pill) individuals. Serum samples were collected from patients’ blood before using the Saffron pills/placebo pills and then after 12 months. The serum level of MMP-9 and its inhibitor, as well as TIMP-1, were measured by ELISA kits. Data were analysed using SPSS version 13. MMP-9 serum levels noticeably decreased in patients with MS following 12 months of treatment with Saffron pills (p=0.006) while the changes were not significant before and after 12 months of treatment with placebo pills. Although the levels of TIMP-1 increased significantly after one year treating with Saffron pills (p=0.0002), a considerable difference was not observed before and after taking the placebo pills. The study finding revealed that 12-months treatment with Saffron could have a significant role in reducing the serum level of MMP-9 and increasing the serum level of TIMP-1 in RRMS patients. Therefore, modulating the serum levels of MMP-9 as an important regulator of T cell trafficking to the CNS might be a promising strategy in the treatment of MS patients.

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Sandro La Vignera ◽  
Rosita A. Condorelli ◽  
Enzo Vicari ◽  
Chiara Nicoletti ◽  
Aldo E. Calogero

This study evaluated the effects of LT4 administration on the bone mineral density (BMD) in physiological postmenopausal women after two years of continuative treatment. 110 postmenopausal women with nodular goiter aged between 50 and 55 years were examined before and after 2 years of therapy with a fixed dose of LT4 (1.6 mcg/kg/die) for the treatment of nodular thyroid disease. The results showed that the patients on treatment with LT4 have a slight, but significant reduction of the BMD after 2 years of treatment, associated with increased serum levels of alkaline phosphatase and urinary excretion of hydroxyproline, confirming our data conducted on the same group after one year of therapy. Comparison between patients receiving LT4 (group A) or not (group B) showed that group A patients had significantly lower BMD. We demonstrated the statistically significant influence of the following risk factors on BMD: (1) body mass index<19 kg/m2; (2) the onset of menarche after the age of 15 years; (3) positive history for period of amenorrhoea; (4) nulliparity.


2022 ◽  
Vol 21 (1) ◽  
pp. 184-190
Author(s):  
Nashwa M Selim ◽  
Somia El Sheikh ◽  
Wafaa S Metwally

Objectives: Allergen-specific immunotherapy (AIT) has been considered the most effective treatment for IgE mediated allergies, especially respiratory allergies. Several biomarkers have been developed to evaluate the clinical efficacy of AIT, yet none of them have been thoroughly validated. So our objective here is to investigate the usefulness of periostin as a biomaker for monitoring the efficacy of allergen immunotherapy. Materials and methods: This study included 46 healthy non-atopic volunteers and 46 patients with allergic rhinitis (AR). They were sensitized only to date palm pollen. The participants were tested by skin prick test and total serum IgE levels were measured. Serum samples were collected from healthy subjects and allergic patients before and after the one-year AIT. Serum levels of periostin, eotaxin, and sIL-2R were estimated by ELISA. Symptom scores in the allergic patients were also evaluated before and after completing one year AIT. Results: There is a significant increase in serum levels of IgE, periostin, sIL-2R, and eotaxin in allergic patients as compared to healthy controls. Symptom scores, sIL-2R and serum periostin levels were significantly decreased after one-year AIT in AR patients. Conclusion: Periostin can be used as a biomarker to evaluate AIT efficacy in AR patients. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 184-190


2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Sameerah Mustafa ◽  
Asal Tawfeeq ◽  
Hadeel Hasan

This study involved the collection of (90) samples of women serum which included (30) serum samples collected from women before menopause (reproductive women) in the age range of (22-43) years and were considered as (group A- control). While, (group B) included (30) serum samples collected from women using oral contraceptive pills between the ages of (22-43) years old. Whereas, another (30) serum samples were collected from women after menopause between the ages of (43-54) years and were considered as (group C). All of the collected serum samples were subjected to a number of serological and chemical tests for the measurement of (E2, HDL, LDL and Ca). Then, the obtained data were statistical analyzed and results showed a significant decrease (p˂ 0.05) in (E2 ,Ca and HDL) levels in menopausal women compared to that of the normal healthy controls. While, there were non-significant decrease (p> 0.05) in (E2, Ca and HDL) levels in women taking oral contraceptive when compared to the normal healthy controls. On the other hand, a significant increase (p˂ 0.05) was recorded in LDL level in menopausal women compared to that of the normal healthy controls whereas, no-significant increase (p˃ 0.05) in the LDL level in women taking oral contraceptives when compared to the control women.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1323.2-1324
Author(s):  
K. Sato ◽  
S. Mamada ◽  
C. Hayashi ◽  
T. Nagashima ◽  
S. Minota

Background:Biologic disease modifying anti-rheumatic drugs (DMARDs) have demonstrated that proinflammatory cytokines such as interleukin (IL-) 6 and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Other cytokines, such as type I interferons (IFNs), are also implicated in its pathogenesis (ref 1). However, the complete picture of the cytokine network involved in RA remains to be elucidated.Objectives:By quantifying sets of cytokines in the serum of RA patients before and after treatment with various biologic DMARDs, we sought to determine the effects of drugs on (A) type I IFNs, (B) soluble IL-6 receptors, and (C) other cytokines.Methods:52 patients with RA were treated with various biologic DMARDs (tocilizumab (TOC): 16, abatacept (ABT): 15, and TNF inhibitors (TNFi): 21). Serum samples were obtained (1) before, (2) approximately 4 weeks after (3) and approximately 12 weeks after the initiation of treatment. A suspension bead-array system was used for analysis; Bio-Plex Human Cytokine 17-plex Assay kits and Express Custom Panels (Bio-Rad), including IFN-β, IFN-α2, soluble IL-6 receptor α (sIL6Rα) and gp130 were used.Results:(1) As expected, the disease activity score 28-joiny count (DAS28) using the erythrocyte sedimentation rate (ESR) significantly decreased in all three groups (TOC, ABT and TNFi) by 12 weeks.(2) IFN-α2 was barely detected in the serum samples. IFN-β seemed to increase slightly in the ABT group, but the increase was not statistically significant.(3) The levels of sIL6Rα did not change substantially. Those of gp130 decreased slightly but significantly in the TOC group by 12 weeks.(4) The levels of IL-6 decreased significantly in the ABT group by 12 weeks. Those in the TNFi group decreased significantly at 4 weeks but not 12 weeks (Fig. 1A).(5) The levels of IL-7 decreased significantly only in the TOC group (Fig. 1B).Conclusion:(1) The biologic DMARDs tested in this study did not significantly affect the serum levels of type I IFNs in this study.(2) The decrease in gp130 in the TOC group may imply that gp130 is induced by IL-6, although whether this level of decrease has physiological significance is open to question.(3) Serum IL-6 was significantly decreased in the TNFi group at 4 weeks but not 12 weeks. TNF has been reported to induce IL-6 (ref 2), but negative feedback loop(s) may be present. Such a feedback system might make the discontinuation of TNFi difficult, even if patients are in remission.(4) IL-7 may be a target of IL-6. A higher level of IL-7 has been reported to be present in the joints of RA patients compared with osteoarthrosis and it is a cytokine implicated in the differentiation of osteoclasts (ref 3). This may partly explain the effect of TOC on preventing bone erosion in RA.References:[1]Ann Rheum Dis. 2007; 66: 1008–14[2]Rheumatology 2007; 46: 920-6[3]Rheumatology 2008; 47: 753-9Acknowledgments:We thank all the members of the Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University. We are also grateful to the patients involved in this study.Disclosure of Interests:Kojiro Sato Grant/research support from: Abbie, Pfizer, Chugai, Astellas, Mitsubishi-Tanabe, Ono, Takeda, Sachiko Mamada: None declared, Chiyomi Hayashi: None declared, Takao Nagashima: None declared, Seiji Minota: None declared


Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 509-517 ◽  
Author(s):  
Silvia Marola ◽  
Alessia Ferrarese ◽  
Enrico Gibin ◽  
Marco Capobianco ◽  
Antonio Bertolotto ◽  
...  

AbstractConstipation, obstructed defecation, and fecal incontinence are frequent complaints in multiple sclerosis. The literature on the pathophysiological mechanisms underlying these disorders is scant. Using anorectal manometry, we compared the anorectal function in patients with and without multiple sclerosis.136 patients referred from our Center for Multiple Sclerosis to the Coloproctology Outpatient Clinic, between January 2005 and December 2011, were enrolled. The patients were divided into four groups: multiple sclerosis patients with constipation (group A); multiple sclerosis patients with fecal incontinence (group B); non-multiple sclerosis patients with constipation (group C); non-multiple sclerosis patients with fecal incontinence (group D). Anorectal manometry was performed to measure: resting anal pressure; maximum squeeze pressure; rectoanal inhibitory reflex; filling pressure and urge pressure. The difference between resting anal pressure before and after maximum squeeze maneuvers was defined as the change in resting anal pressure calculated for each patient.ResultsGroup A patients were noted to have greater sphincter hypotonia at rest and during contraction compared with those in group C (p=0.02); the rectal sensitivity threshold was lower in group B than in group D patients (p=0.02). No voluntary postcontraction sphincter relaxation was observed in either group A or group B patients (p=0.891 and p=0.939, respectively).ConclusionsThe decrease in the difference in resting anal pressure before and after maximum squeeze maneuvers suggests post-contraction sphincter spasticity, indicating impaired pelvic floor coordination in multiple sclerosis patients. A knowledge of manometric alterations in such patients may be clinically relevant in the selection of patients for appropriate treatments and for planning targeted rehabilitation therapy.


2018 ◽  
Vol 28 (4) ◽  
pp. 31668
Author(s):  
Elham Eftekhari ◽  
Masoud Etemadifar

AIMS: To determine the effect of Mat Pilates on serum levels of interleukin-10 and brain-derived neurotrophic factor in women with multiple sclerosis.METHODS: Thirty women with multiple sclerosis with mild to moderate disability were recruited and randomly divided into equal Pilates training and Control groups. Patients in the training group accomplished a Pilates program three times a week for eight weeks. The Control group maintained their routine lifestyle. The serum level of interleukin-10 and brain-derived neurotrophic factor were measured before and after the protocol. The differences between groups were assessed by using analysis of covariance test to compare post-tests by considering covariate pre-tests (assuming a p-value <0.05 as significant).RESULTS: There were no significant changes in interleukin-10 (13.09±5.36 ng/ml in the Pilates training group compared to 13.21±4.76 ng/ml in the Control group, p= 0.81), whereas an increase in brain-derived neurotrophic factor was observed after eight-week Pilates training (11550.14±2619.60 ng/ml in the Pilates training group compared to 9664.35±3161.66 ng/ml in the Control group, p= 0.03).CONCLUSIONS: The results suggest that the intensity and duration of this protocol was not related to significant changes in interleukin-10, but was followed by an increase in brain-derived neurotrophic factor in these patients. Based on this finding, physical activity according to the individual’s ability is recommended for patients with multiple sclerosis, in parallel with drug therapy.


2005 ◽  
Vol 11 (3) ◽  
pp. 360-363 ◽  
Author(s):  
H Zéphir ◽  
J de Seze ◽  
K Dujardin ◽  
G Dubois ◽  
M Cabaret ◽  
...  

We conducted an evaluation of changes in cognition in progressive multiple sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide (700 mg/m2) with methylprednisolone (1 g). Twenty-eight consecutive progressive MS patients (10 primary progressive, 18 secondary progressive MS) were evaluated before and after six and 12 months of treatment. The WAIS-R score, memory and executive functions were evaluated. Under treatment we found a significant improvement in global cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months. However, mechanisms of action of the positive effect of these anti-inflammatory and immunosuppressive treatments on cognition remain unclear.


2012 ◽  
Vol 5 (4) ◽  
pp. 187-198 ◽  
Author(s):  
Charles Pierrot-Deseilligny ◽  
Sophie Rivaud-Péchoux ◽  
Pierre Clerson ◽  
Raphaël de Paz ◽  
Jean-Claude Souberbielle

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 244-244 ◽  
Author(s):  
Hyacinth I Hyacinth ◽  
Beatrice E Gee ◽  
Jenifer H Voeks ◽  
Robert J. Adams ◽  
Jacqueline Hibbert

Abstract Abstract 244 Stroke is a major cause of morbidity and mortality among children with sickle cell anemia (SCA). Children with SCA at risk for stroke can be identified by transcranial Doppler (TCD) ultrasound screening for abnormally high cerebral artery blood flow velocity and strokes can be prevented by chronic packed red blood cell (RBC) transfusion. However, the mechanisms that lead to cerebral vasculopathy and stroke in SCA and that explain the beneficial effects of chronic RBC transfusions in stroke prevention are poorly understood. We have previously shown that pre-treatment serum levels of brain derived neurotropic factor (BDNF) and platelet derived growth factor (PDGF) subtypes, biomarkers of cerebral ischemia and arterial remodeling, were associated with both high TCD velocity and development of stroke. We hypothesized that frequency of RBC transfusion would be associated with altered serum levels of neurodegenerative, inflammatory and angiogenic markers in SCA children with high TCD velocity and tested this hypothesis by assaying levels of these markers in post-STOP serum samples. Frozen serum samples drawn one year after subject's exit from the STOP clinical trial phase were utilized. Given the positive trial results, all but 9 subjects had been on chronic transfusion regimen for at least one year at the time of sample collection. Eighty samples were assayed using multiplex antibody immobilized beads (Millipore Corp, Billerica, MA). The mean fluorescent intensity was measured using the Milliplex xMAP system powered by Luminex (Bio-Rad, Hercules, CA). Ten biologically related neurodegenerative, inflammatory and angiogenic biomarkers were tested. The total number (frequency) of RBC transfusions recorded over the study period (4 years) for each participant was categorized into High (≥ 40), Moderate (20 – 39) or Low (< 20) frequency of transfusion. Median distribution with 10 – 90th percentile of the levels of biomarkers and TCD velocity were expressed using box-plots and the differences in median distribution between groups based on frequency of transfusion was estimated using Kruskal-Wallis test. A principal component analysis (PCA) loading plot was used to demonstrate the biological relationships between the biomarkers, taking into consideration linear correlations and spatial relationships between them. There were no significant differences in the hematological and anthropometric measures between groups. Overall, our result showed that low transfusion frequency was associated with high serum levels of biomarkers and vice versa, despite no significant difference in hemoglobin level between groups. The high frequency transfusion group had lower serum levels of BDNF (p = 0.02), sVCAM-1 (p < 0.001), PDGF-AA (p < 0.001), CCL5 (p < 0.01), tPAI-1 (p < 0.01) and NCAM (p < 0.01) levels compared with the low frequency transfusion group (figure 1 a – e). Although not shown in the figures, the same pattern was observed with TCD velocity which was lower (160, 115.7 – 204.9 cm/s) in the low compared with the high (195, 154 – 272 cm/s) frequency transfusion group. In addition, the medium frequency transfusion group had significantly lower serum sVCAM-1 (p < 0.01) compared with the low frequency transfusion group and higher PDGF-AA (p < 0.01) compared with the high frequency transfusion group. A PCA loading plot (figure 2) shows clustering of the biomarkers that are most closely biologically related, these are also the biomarkers that were significantly affected by the frequency of transfusion. Red blood cell transfusions in the STOP study were associated with reduced serum levels of biomarkers of angiogenesis (PDGF-AA and sVCAM-1), cerebral ischemia/neuronal survival adaptation (BDNF and NCAM) and inflammation (RANTES/CCL5), and this effect was most pronounced in the group with the highest frequency of transfusions (equivalent to most chronic transfusion regimen). This suggests that the protective effects of chronic RBC transfusions on stroke development in children with SCA may be attributable to improved cerebral perfusion, reduced inflammation and down-regulation of hypoxia-induced angiogenic responses that promote arterial remodeling. One or more in this group of biologically-related and relevant markers may be useful for monitoring children with SCA receiving stroke prevention therapies and for designing treatment targets. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7537-7537 ◽  
Author(s):  
M. Reiser ◽  
M. Wenger ◽  
C. Nickenig ◽  
N. Peter ◽  
B. Metzner ◽  
...  

7537 Background: The combination of Rituximab (R) and CHOP is considered the standard of treatment for DLBCL in elderly patients (pts) but there is hardly any data on the pharmacokinetic of Rituximab in aggressive lymphoma pts. The RICOVER-60 trial using Rituximab + bi-weekly CHOP-14 resulted in improved TTF in 828 elderly DLBCL pts (Blood 106:9a, 2005). Objective: To study serum levels and pharmacokinetic properties of Rituximab when combined with CHOP-14 in elderly DLBCL pts. Methods: Blood samples of 20 pts were taken before and after Rituximab infusion at each chemotherapy cycle. Additional samples were taken after the end of treatment and at the following time points: after 1 week, 1 month, 2 months, 3 months, 6 months and 9 months, respectively. Peak serum samples were taken within a maximum of 30 min, all samples were centrifuged at 1000 g for 10 min (room temperature) and stored at −20 degrees C. Batch samples were shipped to Xendo Laboratories, Groningen, The Netherlands, and analysed. Results: Samples from 20 pts were evaluable for this analysis with 16/20 pts having completed all 8 cycles of treatment, yet. The median (range) of serum Rituximab levels (μg/ml) before each cycle were: #1 0 (0–0); #2 39 (13–62); #3 74 (47–109); #4 95 (40–136); #5 111 (55–157); #6 114 (12–518); #7 125 (72–207);#8 116 (75–304). After therapy median (range) of serum Rituximab levels were: 163 (67–248) at 1 week; 101 (44–163) at 1 month; 55 (1–123) at 2 months; 34 (1–577) at 3 months; 5 (0–103) at 6 months; 1 (0–128) at 9 months. At 9 months samples from 7 pts were evaluable with detectable serum Rituximab levels in 4/7 pts. Conclusion: In the dose dense regimen R+CHOP-14 Rituximab levels increased after each subsequent cycle for the first 4 cycles. During cycle 5- 8 the serum Rituximab levels reached a plateau and decreased constantly after the end of treatment with detectable levels even after 9 months. Based on this data the German High Grade NHL Study Group (DSHNHL) further investigates a densification of Rituximab in the first cycles in order to improve treatment outcome. A final analysis of all 20 pts and a pharmacokinetic model of Rituximab distribution and elimination phase will be presented at the meeting. [Table: see text]


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