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Effects of a polysaccharide-based multi-ingredient supplement on salivary immunity in non-elite marathon runners.
Roca, E, Cantó, E, Nescolarde, L, Perea, L, Bayes-Genis, A, Sibila, O, Vidal, S
Journal of the International Society of Sports Nutrition. 2019;16(1):14
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Competing in very strenuous events such as marathons imposes severe metabolic stress and causes acute responses that may negatively alter the immune system. The aim of this study is to determine the impact of Advanced Ambrotose© complex powder (AA) on the levels of salivary secretory Immunoglobulin A (sIgA) [an antibody that plays a critical role in mucosal immunity], pro-inflammatory chemokines and anti-inflammatory proteins before and after running a marathon in non-elite marathoners. The study recruited 41 male participants which were randomly assigned to one of the two groups. Twenty participants (48%) received AA supplementation prior to the race (AA group), whilst the rest did not receive AA supplementation. Supplementation was received for 15 days prior to the marathon. Results indicate that there were no significant differences in age, weight, height, and training were found between runners who received AA supplementation and those who did not. However, findings show significant changes in salivary biomarkers of immune function in healthy, non-elite athletes before and after a strenuous exercise. Authors conclude that AA supplementation produces changes in salivary immunity that may have a positive effect on immunity before and after a marathon.
Abstract
BACKGROUND Extreme exercise may alter the innate immune system. Glycans are involved in several biological processes including immune system regulation. However, limited data regarding the impact of glycan supplementation on immunological parameters after strenuous exercise are available. We aimed to determine the impact of a standardized polysaccharide-based multi-ingredient supplement, Advanced Ambrotose© complex powder (AA) on salivary secretory Immunoglobulin A (sIgA) and pro- and anti-inflammatory protein levels before and after a marathon in non-elite runners. METHODS Forty-one male marathon runners who completed the 42.195 km of the 2016 Barcelona marathon were randomly assigned to two study groups. Of them, n = 20 (48%) received the AA supplement for 15 days prior the race (AA group) and n = 21 (52%) did not receive any AA supplement (non-AA group). Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, pro-inflammatory chemokines (Gro-alpha, Gro-beta, MCP-1) and anti-inflammatory proteins (Angiogenin, ACRP, Siglec 5) were determined using commercially ELISA kits in saliva supernatant. Biochemical parameters, including C-reactive protein, cardiac biomarkers, and blood hemogram were also evaluated. RESULTS Marathon runners who did not receive the AA supplement experienced a decrease of salivary sIgA and pro-inflammatory chemokines (Gro-alpha and Gro-beta) after the race, while runners with AA supplementation showed lower levels of anti-inflammatory chemokines (Angiogenin). Gro-alpha and Gro-beta salivary levels were lower before the race in the AA group and correlated with blood leukocytes and platelets. CONCLUSIONS Changes in salivary sIgA and inflammatory chemokines, especially Gro-alfa and Gro-beta, were observed in marathon runners supplemented with AA prior to the race. These findings suggested that AA may have a positive effect on immune response after a strenuous exercise.
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How to Improve Effectiveness and Adherence to Antihypertensive Drug Therapy: Central Role of Dihydropyridinic Calcium Channel Blockers in Hypertension.
Tocci, G, Desideri, G, Roca, E, Calcullo, C, Crippa, M, De Luca, N, Gaudio, GV, Lonati, LM, Orselli, L, Scuteri, A, et al
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2018;(1):25-34
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Abstract
Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guidelines support a substantial equivalence amongst various antihypertensive drug classes. However, several studies have also reported clinically relevant differences among antihypertensive drugs, in terms of both BP lowering efficacy and tolerability/safety profile. These differences should be taken into account not only when adopting first-line antihypertensive therapy, but also when titrating or modulating combination therapies, with the aim of achieving effective and sustained BP control. This review will briefly describe evidence supporting the use of dihydropyridinic calcium channel blockers for the clinical management of hypertension, with a particular focus on barnidipine. Indeed, this drug has been demonstrated to be effective, safe and well tolerated in lowering BP levels and in reducing hypertension-related organ damage, thus showing a potential key role for improving the clinical management of hypertension.
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Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial.
Romera, A, Peredpaya, S, Shparyk, Y, Bondarenko, I, Mendonça Bariani, G, Abdalla, KC, Roca, E, Franke, F, Melo Cruz, F, Ramesh, A, et al
The lancet. Gastroenterology & hepatology. 2018;(12):845-855
Abstract
BACKGROUND BEVZ92 is a proposed biosimilar to bevacizumab. The two molecules have similar physicochemical and functional properties in in-vitro and preclinical studies. In this clinical study, we compared the pharmacokinetic profile, efficacy, safety, and immunogenicity of BEVZ92 with reference bevacizumab as a first-line treatment in patients with metastatic colorectal cancer. METHODS We did a randomised, open-label trial at 15 centres in Argentina, Brazil, India, Spain, and Ukraine. Eligible patients were aged 18 years or older, had metastatic colorectal cancer with at least one measurable non-irradiated lesion for which first-line chemotherapy was indicated and Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, had not received previous treatment for advanced disease, and whose bone marrow, hepatic, renal, and coagulation markers were all within normal ranges. Patients were randomly assigned (1:1) to either BEVZ92 or reference bevacizumab (5 mg/kg on day 1 of each cycle every 2 weeks) in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI). Randomisation was done via a web service based on a stochastic minimisation algorithm and was stratified by chemotherapy regimen (FOLFOX vs FOLFIRI), previous adjuvant therapy (yes vs no), ECOG performance status (0-1 vs 2), and study site. The primary endpoint was the area under the concentration-versus-time curve after a single infusion (AUC0-336h) and at steady state (AUCss)-ie, at cycle 7-in the assessable population, which comprised all treated patients for whom serum concentration measurements were available during the first seven cycles. Bioequivalence was established if the 90% CIs for the ratio of BEVZ92 to reference bevacizumab of the geometric means for AUC0-336h and AUCss were within the acceptance interval of 80-125%. Secondary endpoints included objective response, clinical benefit, and progression-free survival in the intention-to-treat population and immunogenicity and safety profiles in all treated patients. This trial is registered with ClinicalTrials.gov, number NCT02069704, and is closed to new participants, with follow-up completed. FINDINGS 142 patients were randomly assigned, 71 to the BEVZ92 group and 71 to the reference bevacizumab group. Two participants assigned to BEVZ92 did not receive treatment (one withdrew consent, the other had a serious intestinal obstruction before starting treatment); therefore, the treated population comprised 69 patients in the BEVZ92 group and 71 in the reference bevacizumab group. The geometric mean ratio of AUC0-336h in the BEVZ92 versus the control group was 99·4% (90% CI 90·5-109·0) and of AUCss was 100·0% (90·2-112·0). Objective response (35 [49%] of 71 vs 40 [56%] of 71), clinical benefit (62 [87%] vs 65 [92%]), and progression-free survival (median 10·8 months [95% CI 7·4-11·5] vs 11·1 months [95% CI 8·0-12·8]) were similar in the BEVZ92 and reference bevacizumab groups. No relevant differences were noted between the safety profiles of the two study treatments. Neutropenia was the most common grade 3 or 4 adverse event reported in the BEVZ92 (14 [20%] of 69 patients) and reference bevacizumab (19 [27%] of 71 patients) groups. Serious adverse events occurred in 19 (28%) patients in the BEVZ92 group and 21 (30%) in the reference bevacizumab group. Two patients died because of bevacizumab-related serious adverse events: a sudden death in the BEVZ92 group and a serious large intestinal perforation in the reference bevacizumab group. The occurrence of anti-drug antibodies was low and similar in both treatment groups (two patients in the BEVZ92 group and one in the reference bevacizumab group). INTERPRETATION Our results suggest that BEVZ92 and reference bevacizumab are pharmacokinetically bioequivalent and have no appreciable differences in efficacy, immunogenicity, and safety profiles as first-line treatment in combination with FOLFOX or FOLFIRI in patients with metastatic colorectal cancer. FUNDING mAbxience Research SL.
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Salivary immunity and lower respiratory tract infections in non-elite marathon runners.
Cantó, E, Roca, E, Perea, L, Rodrigo-Troyano, A, Suarez-Cuartin, G, Giner, J, Feliu, A, Soria, JM, Nescolarde, L, Vidal, S, et al
PloS one. 2018;(11):e0206059
Abstract
RATIONALE Respiratory infections are common after strenuous exercise, when salivary immunity may be altered. We aim to investigate changes in salivary immunity after a marathon and its relationship with lower respiratory tract infections (LRTI) in healthy non-elite marathon runners. METHODS Forty seven healthy marathon runners (28 males and 19 females) who completed the 42.195 km of the 2016 Barcelona marathon were studied. Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, antimicrobial proteins (lactoferrin, lysozyme) and chemokines (Groα, Groβ, MCP-1) were determined using ELISA kits in saliva supernatant. Blood biochemistry and haemogram were analyzed in all participants. The presence of LRTI was considered in those runners who reported infectious lower respiratory tract symptoms during a minimum of 3 consecutive days in the 2 weeks after the race. RESULTS Eight participants (17%) presented a LRTI during the 2 weeks of follow-up. Higher lysozyme levels were detected after the race in runners with LRTI when compared with those without infection. A decrease in salivary lysozyme, Groα and Groβ levels after the race were observed in those runners who did not develop a LRTI when compared to basal levels. Salivary Groα levels correlated with basophil blood counts, and salivary lysozyme levels correlated with leukocyte blood counts. CONCLUSIONS LRTI are common after a marathon race in non-elite healthy runners. Changes in salivary antimicrobial proteins and chemokines are related to the presence of LRTI and correlate with systemic defense cells, which suggest an important role of salivary immunity in the development of LRTI in non-elite marathon runners.
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Sarcomere Disruptions of Slow Fiber Resulting From Mountain Ultramarathon.
Carmona, G, Roca, E, Guerrero, M, Cussó, R, Irurtia, A, Nescolarde, L, Brotons, D, Bedini, JL, Cadefau, JA
International journal of sports physiology and performance. 2015;(8):1041-7
Abstract
OBJECTIVE To investigate changes after a mountain ultramarathon (MUM) in the serum concentration of fast (FM) and slow (SM) myosin isoforms, which are fiber-type-specific sarcomere proteins. The changes were compared against creatine kinase (CK), a widely used fiber-sarcolemma-damage biomarker, and cardiac troponin I (cTnI), a widely used cardiac biomarker. METHODS Observational comparison of response in a single group of 8 endurance-trained amateur athletes. Time-related changes in serum levels of CK, cTnI, SM, and FM from competitors were analyzed before, 1 h after the MUM, and 24 and 48 h after the start of the MUM by 1-way ANOVA for repeated measures or Friedman and Wilcoxon tests. Pearson correlation coefficient was employed to examine associations between variables. RESULTS While SM was significantly (P = .009) increased in serum 24 h after the beginning of the MUM, FM and cTnI did not change significantly. Serum CK activity peak was observed 1 h after the MUM (P = .002). Moreover, serum peaks of CK and SM were highly correlated (r = .884, P = .004). CONCLUSIONS Since there is evidence of muscle damage after prolonged mountain running, the increase in SM serum concentration after a MUM could be indirect evidence of slow- (type I) fiber-specific sarcomere disruptions.
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A phase I/II and pharmacogenomic study of pemetrexed and cisplatin in patients with unresectable, advanced gastric carcinoma.
Chen, JS, Chao, Y, Bang, YJ, Roca, E, Chung, HC, Palazzo, F, Kim, YH, Myrand, SP, Mullaney, BP, Shen, LJ, et al
Anti-cancer drugs. 2010;(8):777-84
Abstract
This phase I/II study was conducted to determine the maximum recommended dose of pemetrexed when given in combination with a fixed dose of cisplatin, and the efficacy, toxicity and association of 5,10-methylenetetrahydrofolate reductase (MTHFR) variants with this pemetrexed--cisplatin combination, in patients with unresectable, advanced gastric carcinoma. Patients 18-70 years of age, with stage IV disease or post-surgery recurrence, no earlier palliative chemotherapy, 0 or 1 Eastern Cooperative Oncology Group performance status, were included. The cisplatin dose was 75 mg/m. In phase I, the initial dose of pemetrexed was 600 mg/m, escalated in 100 mg/m increments. In phase II, efficacy, including overall response rate, overall survival, as well as toxicity and MTHFR pharmacogenetics were investigated. Phase I enrolled 16 patients; 700 mg/m was defined as pemetrexed recommended dose. Thirteen serious adverse events were reported; the most common grade 3/4 toxicities were haematologic (10 of 13, 76.9%). Phase II enrolled 73 patients, 69 qualified for safety and 68 for efficacy analysis; 65 for pharmacogenomic analysis. Overall response rate was 23.5% (14.1%, 35.4%), disease control rate 55.9%, median overall survival 11.8 months (95% confidence interval, 7.2-18.5 months), progression-free survival 4.9 months (95% confidence interval, 2.8-7.1 months), and median response duration 5.4 months. Patients with MTHFR A1298C variants had median overall survival of 6.6 months, significantly shorter than patients with the wild type (median 18.5 months, P=0.001). The pemetrexed--cisplatin combination in patients with advanced gastric cancer generates modest efficacy and a manageable toxicity profile. The reduced overall survival in patients with MTHFR A1298C polymorphism variants deserves further investigation.