Reduction In CRP Levels Research Articles

P0679 Therapeutic Drug Monitoring of the Infliximab (anti-TNF) Level with Bedside Kit in Inflammatory Bowel Disease

Abstract Background Approximately half (10-40%) of the Inflammatory Bowel Disease (IBD) patients using Infliximab (IFX) develop secondary loss of response due to drug levels falling below the therapeutic range. This study aims to identify drug levels, influencing factors and parameters that may be useful in predicting target drug levels. Methods The pre-infusion drug levels and associated laboratory parameters were evaluated in IBD patients on maintenance dose of IFX (5-15 mg/kg every 4-8 weeks) between Nov2021 - Oct2024. Drug levels were measured using a bedside kit capable of quantitatively detecting values between 0.4-20 µg/ml. Results In total, 931 single pre-infusion measurements from 415 different patients, and dual measurements at weeks 4 and 8 from 116 patients were separately evaluated. 82% of the patients in the single measurement group, and 84% in the double measurement group had Crohn’s disease(CD), rest having Ulcerative Colitis. The most used doses in the single measurement group were 5 mg/8 weeks and 10 mg/4 weeks (Table 1). In the single measurement group, median albumin was 4.4 (IQR: 0.5), and median CRP was 3.1 (IQR: 6.4). Drug levels were below 5 µg/ml in 33% of measurements. CRP showed a significant difference according to drug level groups (Table 2), while no such difference was observed for albumin. In the measurable IFX range (0.4-20 µg/ml), correlation analysis revealed a weak negative correlation between CRP and drug levels (r: -0.09, p: 0.03). Regression analysis showed that lower CRP, higher drug dose, and CD diagnosis were independently associated with achieving >5 µg/ml drug levels. In the dual measurement group: The median CRP levels of patients at weeks 4 and 8 were 2.1 (5.1) and 2.6 (6.2), respectively (p>0.05). Among patients with IFX levels >20 µg/ml at week 4, 79% maintained levels >5 µg/ml at week 8, while this rate dropped to 71% for those with levels >10 µg/ml. Only 67% of patients with levels >5 µg/ml at week 4 maintained a level of >5 µg/ml at week 8 (all p-values <0.001). Conclusion As drug levels increase, significant reductions in CRP levels are observed. Therefore, low CRP levels may predict the likelihood of achieving the therapeutic range. Dose adjustment should be considered in cases with high CRP levels. Achieving a high drug level (>20 µg/ml) at 4th week is an important indicator of achieving at least an acceptable drug level (>5 µg/ml) at the end of treatment. (8th week).

Effect of Pentoxifylline on Inflammatory Marker in Non-Diabetic Chronic Kidney Disease Patients

Abstract Background Chronic kidney disease is a progressive condition that affects >10% of the general population worldwide, amounting to > 800 million individuals in 2017. CKD has emerged as one of the most prominent causes of death and suffering in the 21st century. Aim of the Work To assess the effect of pentoxifylline on inflammatory marker and Chronic Kidney Disease progression in non- diabetic chronic kidney disease. Patients and Methods The current study design was a prospective, interventional, open- label, randomized controlled clinical trial conducted on adult patients with Chronic Kidney Disease at the outpatient clinics of AinShams University hospital, Cairo, Egypt, from the start of February (2023) to the end of July (2023). Results TNF-alpha, CRP, UPCR, and GFR were measured at baseline and after a six-month follow-up period. TNF-alpha and CRP levels were determined using enzyme-linked immunosorbent assay (ELISA) kits, while UPCR was calculated by dividing the urinary protein concentration by the urinary creatinine concentration. GFR was estimated using CKD-EPI. The results of this study showed a significant decrease in CRP levels in group 2 compared to group 1, indicating a greater reduction in systemic inflammation with the addition of Pentoxifylline. Similarly, UPCR decreased significantly in group 2, suggesting a beneficial effect of Pentoxifylline on proteinuria. In contrast, there was no statistical difference in the reduction of TNF-alpha levels between the two groups, although both groups exhibited a significant decrease in TNF-alpha. Furthermore, there was no significant difference in GFR changes between the two groups. Conclusion The addition of pentoxifylline to the standard therapy in non-diabetic CKD patients resulted in a significant reduction in CRP levels and proteinuria, indicating its potential as an adjunctive treatment to mitigate inflammation and proteinuria. However, no significant difference was observed in the reduction of TNF-alpha levels or GFR changes between the two groups. These findings suggest that pentoxifylline's anti-inflammatory effects may be mediated through pathways other than TNF-alpha inhibition. Further research is warranted to explore the underlying mechanisms and optimize the use of pentoxifylline in the management of CKD patients.

The Role of Zinc Supplementation in Alleviating Inflammatory Biomarkers in Patients Undergoing Hemodialysis: A Randomized Placebo Controlled, Crossover Trial.

Chronic kidney disease (CKD), which progresses to end-stage renal disease (ESRD) and requires maintenance hemodialysis (MHD), is a global health issue. Inflammation in MHD patients is associated with increased mortality and cardiovascular events. Zinc, essential for immune function and possessing anti-inflammatory properties, is frequently deficient in these patients and could potentially help mitigate inflammation. This study aims to assess the impact of zinc supplementation on inflammatory biomarkers, specifically (CRP) and the neutrophil-to-lymphocyte ratio (NLR), in MHD patients. In a double-blind, randomized controlled crossover trial conducted at Labafinejad Hospital, Tehran, MHD patients with zinc deficiency were initially allocated to either a zinc supplementation group or a placebo group. After 30 days, the groups were crossed over, with patients initially receiving zinc now receiving a placebo and vice versa. The primary outcome was changes in serum zinc levels, while secondary outcomes focused on CRP and NLR levels. Significant changes in serum zinc levels were observed in both groups from baseline to Month 2 (drug-placebo group: Mean change -15.9±10.33 µg/dL, P < 0.05; placebo-drug group: Mean change -14.70 ± 12.58 µg/dL, P < 0.05). A significant initial reduction in CRP levels at Month 1 (P = 0.045) was not sustained at Month 2 (P = 0.812). No statistically significant changes in NLR were noted. Improvements in quality of life, including reductions in muscle pain and skin dryness, were significant in the drug-placebo group (P < 0.05). Zinc supplementation in MHD patients significantly improved serum zinc levels and initially reduced CRP levels, highlighting its potential role in managing inflammation. Although the impact on NLR was not significant, overall patient outcomes and quality of life showed promising improvements.

Clinical and Haematological Study of Hijama-Bi’l-Shart (Wet Cupping) In the Management of Pain

Background: This randomized clinical and haematological study evaluated the effect of Hijama-Bil-Shart (Wet Cupping) on musculoskeletal pain and inflammatory markers in venous and cupped blood. Materials and Methods: 110 patients with musculoskeletal pain were screened, with 90 diagnosed and included. After 30 subjects were lost to follow-up, 60 completed the study. Participants received 4 weekly sessions of wet cupping therapy over 4 weeks. Pain intensity was measured using VAS and KOOS scores, and inflammatory markers (Serum uric acid &amp; CRP) were assessed in venous and cupped blood. Results: Pain relief, measured by VAS, showed significant improvement across various musculoskeletal conditions: cervical spondylosis, frozen shoulder, low backache, sciatic pain, knee osteoarthritis, gout, and rheumatoid arthritis. KOOS scores for knee osteoarthritis improved significantly. Serum uric acid levels in venous blood were suggestively insignificant, while CRP levels decreased gradually but were not statistically significant. No adverse effects were reported. Conclusion: Hijama-Bil-Shart (wet cupping) therapy is effective in relieving musculoskeletal pain and improving quality of life. It shows long-term benefits with sustained pain relief and gradual reduction in CRP levels. However, it is not effective in significantly reducing raised serum uric acid levels. Keywords: Musculoskeletal pain, Wet cupping, VAS, KOOS, Hijama-Bil-Shart, CRP

E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation. This study aimed to assess the clinical characteristics and severity of FMF in patients homozygous for the p.E148Q variant and to evaluate the impact of the p.V726A variant in these patients. This retrospective cohort study analyzed data from electronic medical records at Carmel Medical Center, Israel. Patients who underwent genetic testing for FMF from November 2004 to December 2019 and had p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants were included. Disease severity was assessed using the Tel Hashomer Key to Severity Score. Statistical analyses compared clinical characteristics and severity between genotype groups. The study included 61 FMF patients, with 24 (39%) having p.E148Q/p.E148Q and 37 (61%) having p.E148Q/p.E148Q + p.V726A variants. The majority (72%) were Druze. Most patients (65.5%) exhibited mild disease, while 31.1% had moderate disease, with no cases of severe disease. Colchicine treatment significantly reduced CRP levels in all patients.Conclusion: These findings suggest that the p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity, supporting its pathogenic role in particular ethnicity. These results contribute to understanding the clinical significance of the p.E148Q variant and considering the patient’s need for Colchicine treatment.What is Known:• The role of the p.E148Q variant in FMF is debated, with questions about whether it is a benign polymorphism or a pathogenic mutation.• The prevalence of MEFV variants can vary significantly among different ethnic groups.What is New:• The p.E148Q variant has clinical significance in particular ethnicities, as supported by a significant reduction in CRP levels following colchicine treatment.• The p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity.

Guideline-Optimised Treatment in Heart Failure-Do Higher Doses Reduce Systemic Inflammation More Significantly?

Background: Chronic inflammation is a constant phenomenon which accompanies the heart failure pathophysiology. In all phenotypes of heart failure, irrespective of the ejection fraction, there is a permanent low-grade activation and synthesis of proinflammatory cytokines. Many classes of anti-remodelling medication used in the treatment of chronic heart failure have been postulated to have an anti-inflammatory effect. Methods: This retrospective study enrolled 220 patients and focused on evaluating the effect of the most used active substances from these classes in reducing the level of inflammatory biomarkers (C reactive protein, erythrocyte sedimentation rate and fibrinogen) after initiation or up-titration. Our research is evaluating if this anti-inflammatory effect intensifies while raising the dose. The evaluation was performed at two visits with an interval between them of 6 months. Results: From the beta-blockers class, carvedilol showed a reduction in erythrocyte sedimentation rate (ESR), in low (6.25 mg, bi daily) and medium (12.5 mg, bi daily) doses. At the same time, sacubitril/valsartan showed a reduction in CRP levels. This effect was obtained only in the medium (49/51 mg, bi daily) and high (97/103 mg, bi daily) doses, with the maximum reduction being observed in the high dose. Conclusions: From the classes of medication evaluated, the study showed a significant reduction in ESR levels in the low and medium doses of carvedilol and a reduction in CRP values in the cases of medium and high doses of ARNI.

Combining Aerobic Exercise with Fasting Protocols for Effective Obesity Control in Women

Objective: The objective of this narrative review is to systematically evaluate the combined effects of aerobic exercise and fasting protocols on obesity control in women. Methods and Materials: A comprehensive literature search was conducted using databases such as PubMed, Scopus, Web of Science, and Google Scholar. Studies included involved adult women with overweight or obesity, investigating the effects of aerobic exercise, fasting protocols, or their combination on weight loss and metabolic health. Data were extracted on study design, participant characteristics, interventions, outcomes, and key findings. The quality of the included studies was assessed using standardized tools, and a descriptive analysis approach was employed to synthesize findings. Findings: The review found that both aerobic exercise and fasting protocols individually promote significant weight loss and improve metabolic health markers in obese women. Combined interventions lead to greater reductions in body weight and fat, enhanced insulin sensitivity, and improved lipid profiles compared to either strategy alone. For instance, combining aerobic exercise with intermittent fasting resulted in weight loss of up to 10% over 12 weeks, and a significant reduction in body fat percentage. Improvements in inflammatory markers, such as a reduction in CRP levels by 20%, were also noted. The synergistic effects are attributed to complementary mechanisms, including enhanced energy expenditure, improved metabolic flexibility, hormonal regulation, and reduced inflammation. Conclusion: Combining aerobic exercise with fasting protocols is a highly effective strategy for obesity control in women, leading to significant and sustained weight loss, improved body composition, and enhanced metabolic health. These interventions are supported by robust mechanistic insights and practical benefits, making them a valuable addition to comprehensive obesity management programs. Further research should focus on long-term effects, optimal protocols, and diverse populations to refine and expand the application of these combined approaches.

Impact of anakinra use on clinical outcomes in children with moderate or severe multisystem inflammatory syndrome in children: a propensity score matched retrospective cohort study

BackgroundThe treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C.MethodsWe included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher’s exact tests.ResultsOf 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS.ConclusionsIn patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay.

Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients.

Covid-19 is an infectious disease associated with cytokine storms and derailed sympatho-vagal balance leading to respiratory distress, hypoxemia and cardiovascular damage. We applied the auricular vagus nerve stimulation to modulate the parasympathetic nervous system, activate the associated anti-inflammatory pathways, and reestablish the abnormal sympatho-vagal balance. aVNS is performed percutaneously using miniature needle electrodes in ear regions innervated by the auricular vagus nerve. In terms of a randomized prospective study, chronic aVNS is started in critical, but not yet ventilated Covid-19 patients during their stay at the intensive care unit. The results show decreased pro-inflammatory parameters, e.g. a reduction of CRP levels by 32% after 1 day of aVNS and 80% over 7 days (from the mean 151.9 mg/dl to 31.5 mg/dl) or similarly a reduction of TNFalpha levels by 58.1% over 7 days (from a mean 19.3 pg/ml to 8.1 pg/ml) and coagulation parameters, e.g. reduction of DDIMER levels by 66% over 7 days (from a mean 4.5 μg/ml to 1.5 μg/ml) and increased anti-inflammatory parameters, e.g. an increase of IL-10 levels by 66% over 7 days (from the mean 2.7 pg/ml to 7 pg/ml) over the aVNS duration without collateral effects. aVNS proved to be a safe clinical procedure and could effectively supplement treatment of critical Covid-19 patients while preventing devastating over-inflammation.

Potential of the Combination of a Systemic Enzyme Complex and Probiotics administration to Combat COVID-19: A Randomized Open Label Prospective Analysis

Background: Enzymes have been used for therapeutic applications for decades owing to their anti-inflammatory and immunomodulatory effects. Probiotics are well known to reduce the incidence and severity of several health-related conditions. To our knowledge, no clinical trial has evaluated the effects of a combination of systemic enzyme and probiotic supplementation in Covid-19 patients infected with the SARSCoV-2 virus. Objective: We investigated the safety and efficacy of the health supplements ImmunoSEB (systemic enzyme complex) and ProbioSEB CSC3 (probiotic complex) as supplemental therapy in confirmed mild to moderate COVID-19 patients. Methods: A randomized, open label, 2-arm, prospective study in patients with an RT-PCR confirmed diagnosis of COVID-19 with a mild to moderate condition was conducted. The control arm (n=30) received standard of care (SOC) treatment and the test arm (n=30) received the oral supplements ImmunoSEB (500 mg/cap.) + ProbioSEB CSC3 (5 billion CFUs /cap.) for 14 days in addition to SOC. The efficacy and safety of the experimental regimen was compared with the control arm at various timepoints from days 1 to 21. Results: A significantly higher proportion of patients in the test arm showed clinical improvement on day 10 vs the controls (93.33% vs 60%; p&lt;0.05). No adverse events were reported in the test arm at any time during the study suggesting the safety of supplementation with ImmunoSEB + ProbioSEB CSC3. Patients in the test arm also had a shorter duration of hospitalization, quicker recovery and faster reduction in CRP levels as compared to the control arm. Conclusions: The present study concludes that supplemental therapy with ImmunoSEB + ProbioSEB CSC3 accelerates clinical improvement in mild to moderate COVID-19 patients. While there is no vaccine or specific drug to completely cure SARS CoV-2 infection, the proposed supplemental therapy could be a potential tool to aid in the recovery of COVID-19 of patients.

O03 A case of hyperinflammatory COVID-19 that responded to tocilizumab therapy

O03 A case of hyperinflammatory COVID-19 that responded to tocilizumab therapy

P273 Ustekinumab and guselkumab treatment results in differences in serum IL-17A, IL-17F and CRP levels in PsA patients: a comparison from ustekinumab Phase 3 and guselkumab Phase 2 programmes

Abstract Background Ustekinumab (UST) is a monoclonal antibody (mAb) that binds the p40 epitope which is shared by IL-12 and IL-23, whereas guselkumab (GUS) is a mAb that selectively binds the p19 subunit of IL-23. In recent studies, both UST (Phase 3 programs) and GUS (Phase 2 program) have demonstrated a reduction in musculoskeletal clinical signs and symptoms and improvement of psoriatic lesions in patients with active psoriatic arthritis (PsA), implicating the IL-12/23 pathway in disease pathogenesis. This analysis explored the post-treatment pharmacodynamic changes of IL-17A, IL-17F, and CRP with GUS and UST in the context of PsA. Methods Serum protein levels of IL-17A, IL-17F, and CRP were measured in 142 subjects and 38 matched healthy controls from the GUS Phase 2 study at Week (W)0, W4, and W16. In the UST Phase 3 studies, biomarkers were assayed at W0, W4, and W24 as follows: IL-17A (n = 474), IL-17F (n = 237), CRP (n = 927). IL-17A and IL-17F were assayed using Single Molecule CountingTM Human Immunoassay Kits (formerly Singulex). CRP was measured using CardioPhase hsCRP assay (UST studies) or Meso Scale Discovery Platform (GUS study). Results At baseline, the Th17 effector cytokines IL-17A and IL-17F were elevated in the serum of PsA subjects in the GUS Phase 2 cohort compared to healthy controls. IL-17A and IL-17F levels significantly correlated with affected skin body surface area, but not swollen or tender joint scores, in both studies. While none of the baseline levels of evaluated cytokines were associated with American College of Rheumatology (ACR) or Psoriasis Area Severity Index (PASI) clinical responses to UST, baseline IL-17F levels were modestly associated with ACR20 response to GUS at Week 24. Both UST and GUS treatment resulted in pharmacodynamic decreases in IL-17A, IL-17F, and CRP levels, with GUS treatment restoring IL-17A and IL-17F levels to that of healthy controls by W16. Consistent with being a component of ACR scores, CRP changes were significantly associated with ACR20 responses to both UST and GUS treatment. W4 and W16 changes in IL-17F with GUS treatment were significantly associated with ACR20 response at W24. W24 PASI75 response to GUS was significantly associated with W4 changes in IL-17A, with a similar trend observed at W16. Conclusion These results underscore the relevance of the IL-23/Th17 pathway in PsA, with GUS treatment providing a stronger suppression of the pathway than UST treatment. The significant associations of changes in IL-17A and IL-17F levels with GUS treatment with PASI75 and ACR20 response, respectively, support the importance of the IL-23/Th17 pathway for both skin and joint pathologies. The associations of reduction in CRP levels with both UST and GUS treatment also reinforce the role of acute phase inflammation in joint pathology. Disclosures S. Siebert: Other; S.S. has been a study investigator for Janssen. M.J. Loza: Other; M.L. is a Janssen employee. Q. Song: Other; Q.S. is a Janssen employee. P.C. Gorecki: Other; P.G. is a Janssen employee. I.B. McInnes: Other; I.M. has been a study investigator for Janssen. K. Sweet: Other; K.S. is a Janssen employee.

The Low Dose Colchicine after Myocardial Infarction (LoDoCo-MI) study: A pilot randomized placebo controlled trial of colchicine following acute myocardial infarction

We conducted a randomized, double-blind, trial of low-dose colchicine (0.5 mg daily) or matching placebo in 237 patients admitted with an acute MI. The primary end-point was the proportion of patients with a residual high sensitivity CRP level ≥2 mg/L after 30 days of treatment, a threshold associated with a worse prognosis. At 30-day follow-up, 44% of patients treated with colchicine had a CRP level ≥2 mg/L compared to 50% of those randomized to placebo (P = .35) and the median CRP in patients randomized to colchicine was 1.6 mg/L (interquartile range [IQR] 0.7-3.5) compared to 2.0 mg/L (IQR 0.9-4.0) in patients randomized to placebo (P = .11). The median absolute reduction in CRP levels was -4.3 mg/L (IQR -1.1 to -14.1) among colchicine treated patients and -3.3 mg/L (IQR -0.9 to -14.4, P = .44) in placebo treated patients. The relative reduction was a fall of 78% compared to a fall of 64% (P = .09). Low dose colchicine was well tolerated and did not reduce compliance with other secondary preventative medications at 30-days. Treatment with low dose colchicine was safe and well tolerated, but was not associated with a significantly increased likelihood of achieving a CRP level <2 mg/L or lower absolute levels of CRP 30 days after an acute MI.

Clinical predictors of response to anakinra in patients with heart failure

Clinical predictors of response to anakinra in patients with heart failure

Should C-Reactive Protein Be a Target of Therapy?

Multiple studies have demonstrated that elevated levels of high-sensitivity C-reactive protein (hs-CRP) are associated with increased cardiovascular (CV) risk. Newer CV risk stratification strategies incorporating hs-CRP (e.g., Reynolds Risk Score) have also been shown to improve risk stratification better than algorithms incorporating only traditional risk factors. There is also evidence from several landmark statin trials that on-treatment hs-CRP levels predict the likelihood of CV events. Although there is increasing evidence that CRP may be directly involved in the pathogenesis of atherosclerosis, the question of whether reduction in CRP levels and/or its associated downstream effects will provide novel therapeutic avenues to reduce CV risk requires further investigation. CV diseases are the number one cause of mortality worldwide (1). Recent efforts directed at primary prevention of atherosclerosis have significantly reduced the incidence of initial clinical presentation of atherosclerosis. It is well established that patients with known diabetes or other traditional CV risk factors have an increased risk of atherosclerosis. Nonetheless, 15–20% of major CV events occur in patients with no major traditional CV risk factors (2). As a result, recent preventive efforts have been directed at finding newer, nontraditional, biomarkers to improve risk stratification, particularly in otherwise apparently low-risk individuals. hs-CRP, previously considered to be an indicator of systemic inflammation, has recently received much attention in the scientific literature, not only as a potential marker of increased atherosclerotic risk, but also as a potential target of therapy for the prevention of atherosclerotic CV disease. In this review, we discuss whether hs-CRP should indeed be a target for therapy in the prevention of CV disease as well as other potential clinical implications related to hs-CRP. Multiple studies have demonstrated that elevated levels of hs-CRP are clearly associated with increased CV risk (3,4). However, considerable controversy exists on whether CRP itself is …

Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study

BackgroundThe objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on joint health in overweight and normal weight adults diagnosed with osteoarthritis.MethodsAn 8-week placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo on overweight and normal weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts; Phellodendron amurense bark and Citrus sinensis peel) or matching placebo were given in a dose of two capsules (370 mg each) twice daily. The outcome measures were the Lequesne Algofunctional Index (LAI) for joint pain and movement as well as biomarkers of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]).ResultsEighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. The mean total LAI scores at baseline for the four groups ranged from 11.4 to 12.4 (SD 1.2 to 2.4). Treatment for 8 weeks resulted in a statistical improvement in the LAI score in the overweight treatment group compared to placebo (6.3 ± 2.3 vs 11.8 ± 1.5; p < 0.0001). At 8 weeks, a similar result was observed in the normal weight groups (7.7 ± 1.4 vs 9.9 ± 0.9; p < 0.0001). There was a reduction in CRP levels with treatment in the overweight treatment group at 8 weeks (-0.62 ± 0.2; 49%) compared to baseline (p < 0.001) and to placebo (p < 0.001). For the normal weight participants, there were significant reductions in CRP compared to baseline, but not to the matched placebo group. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks. There was no significant change in ESR in any of the groups.ConclusionIn this pilot study, NP 06-1 had beneficial effects on symptoms of osteoarthritis of the knee as measured using LAI scores and had anti-inflammatory effects as measured using CRP. Administration of NP 06-1 was also associated with weight loss, which may have been a contributing factor to the other benefits.

Inflammatory Response to Exercise Training in Chronic Kidney Disease

Excessive inflammation associated with chronic kidney disease (CKD) is believed to contribute to a variety of CKD co-morbidities, including renal osteodystrophy and cardiovascular disease. Endurance exercise training has anti-inflammatory effects in healthy populations, but little is known about the effects of exercise on inflammation in the setting of CKD. Here we present data examining the effects of 4 months of endurance exercise training on inflammation and associated disease risk factors in a mouse model of CKD and in renal disease patients receiving hemodialysis treatment. METHODS. Animal study: Uremia was surgically induced in ApoE-/- mice by 5/6th nephrectomy, then mice were randomly assigned to a sedentary (SED) or exercise training (EX) group for 4 months; EX mice ran on a treadmill 5 days/week for 45 minutes at ∼ 15 meters/min for 4 months. At sacrifice, circulating pro- and anti-inflammatory cytokine levels, aortic atherosclerosis and vascular calcification, and bone density (femur) was measured. Human study: 16 hemodialysis patients were randomly assigned to a SED or EX group for 4 months; those in the EX group cycled 3 days per week during their dialysis session for 45 minutes at a moderate intensity. Blood samples collected at baseline and after the intervention were used to measure circulating inflammatory variables (C-reactive protein; CRP), and markers of oxidative stress (TBARS, lipid peroxidation, and paraoxonase activity). In addition, ultrasound was used to measure arterial and cardiac structure and function. RESULTS: Exercise training had little effect on circulating inflammatory markers, aortic atherosclerosis, or vascular calcification in uremic mice. In dialysis patients, TBARS and lipid peroxidation were both significantly reduced in EX (65% and 12%, respectively, p< 0.05 for both), but did not change in SED, and there was a trend for a reduction in CRP levels in EX (p = 0.08), but not SED. Furthermore, the thickness of epicardial fat, a highly pro-inflammatory visceral fat depot related to cardiovascular disease risk, was also reduced in dialysis patients in EX (12%, p< 0.05), but not SED. CONCLUSIONS: These data suggest that endurance exercise training has modest or no effects on circulating markers of inflammation in either uremic mice or dialysis patients, possibly to the excessive inflammation in CKD, yet may still improve other factors related to inflammation and CVD risk in dialysis patients.

C-Reactive Protein and Hypertension: Is there A Causal Relationship?

There is a large body of evidence indicating that inflammation plays a crucial role in all steps characterizing the atherosclerotic process. C-Reactive Protein is a circulating marker of inflammation which recently emerged as a powerful independent determinant of cardiovascular events. Hypertension is closely linked to inflammation. Experimental data and results from cross-sectional studies in humans indicate a relationship between CRP levels and blood pressure. In particular, CRP seems to be related with markers of arterial stiffness, thus suggesting a specific interaction between CRP and systolic blood pressure. However, such observational studies cannot provide any direct evidence for a cause-effect relation. Prospective studies are likely candidates to better define the putative causal relationship on this association. Available results from longitudinal studies are scanty, and do not allow to draw definitive conclusions. Moreover, prospective, placebo-controlled intervention trials documenting that reduction of CRP levels by pharmacological treatment might lead to a reduced risk to develop hypertension are not yet available. Without such crucial information, at the present time the causal connection between inflammation and blood pressure, although regarded as an intriguing possibility, remains undiscovered.

Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin ± acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA 1c by 0.6 ± 0.9% ( p < 0.005), 1.2 ± 1.3% ( p < 0.0005) and 1.3 ± 1.4% ( p < 0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin ± acarbose also showed a significant reduction in HbA 1c ( p < 0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by −2.6 (3.9) mg/L ( p < 0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.

Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus

Objective: Statins are known to reduce CRP concentrations, but whether high doses are more effective is not known. Methods: In a prospective double-blind multicenter study in 186 DM2 patients without manifest coronary artery disease and with dyslipidemia, the effect of a 30-week treatment with 10 and 80 mg atorvastatin or placebo on the reduction of hs-CRP levels was measured. Results: Median CRP levels increased with 6.6% in the placebo group and were reduced by 15 and 47%, respectively, with atorvastatin 10 and 80 mg ( P<0.001; significantly different from 10 mg atorvastatin and from placebo ( P<0.001). Variation in IL-6 and plasma lipids associated for 21 and 8%, respectively, with variation in CRP levels ( P<0.001 and P=0.01). Of patients with a baseline CRP level above an arbitrary threshold of 3.0 mg/l, 56% in the 80 mg atorvastatin group reached a level of less than 3.0 mg/l, versus 23% randomized to 10 mg atorvastatin ( P<0.01) and 17% in the placebo group ( P<0.005). Conclusions: In DM2 patients high dose atorvastatin induced a strong reduction in CRP levels. The decrease in CRP was mainly independent of effects on lipid lowering and changes in IL-6 levels. The pleiotropic effect of high-dose atorvastatin on inflammation could add to its cardioprotective effect in high-risk patients.