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Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.
Costa, G, Shushanof, M, Bouskela, E, Bottino, D
Journal of vascular research. 2022;(1):24-33
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Abstract
OBJECTIVE The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.
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Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults.
Casey, DP, Bock, JM
American journal of physiology. Heart and circulatory physiology. 2021;(3):H991-H998
Abstract
Aging causes deleterious changes in resting conduit artery shear patterns and reduced blood flow during exercise partially attributable to reduced nitric oxide (NO). Inorganic nitrate increases circulating NO bioavailability and may, therefore, improve age-associated changes in shear rate as well as exercise hyperemia. Ten older adults (age: 67 ± 3 yr) consumed 4.03 mmol nitrate and 0.29 mmol nitrite (active) or devoid of both (placebo) daily for 4 wk in a randomized, double-blinded, crossover fashion. Brachial artery diameter (D) and blood velocity (Vmean) were measured via Doppler ultrasound at rest for the characterization of shear profile as well as during two handgrip exercise trials (4 and 8 kg) for calculation of forearm blood flow (Vmean × cross-sectional area, FBF) and conductance [FBF/mean arterial pressure, forearm vascular conductance (FVC)]. Plasma [nitrate] and [nitrite] increased following active (P < 0.05 for both) but not placebo (P = 0.68 and 0.40, respectively) supplementation. Neither mean nor antegrade shear rate changed following either supplement (beverage-by-time P = 0.14 and 0.21, respectively). Retrograde (-13.4 ± 7.0 to -9.7 ± 6.8·s-1) and oscillatory (0.20 ± 0.08 to 0.15 ± 0.09 A.U., P < 0.05 for both) shear decreased following active, but not placebo (P = 0.81 and 0.70, respectively), supplementation. The FBF response (Δ from rest) to neither 4-kg nor 8-kg trials changed following either supplement (beverage-by-time P = 0.53 and 0.11, respectively). Similarly, no changes were observed in FVC responses to 4-kg or 8-kg trials (beverage-by-time P = 0.23 and 0.07, respectively). These data indicate that inorganic nitrate supplementation improves conduit artery shear profiles, but not exercise hyperemia, in older adults.NEW & NOTEWORTHY We report for the first time, to our knowledge, that 4 wk of inorganic nitrate supplementation attenuates retrograde and oscillatory shear in the brachial artery of older adults. However, this was not associated with greater hyperemic or vasodilatory responses to exercise. In sum, these data highlight favorable changes in shear patterns with aging, which may reduce the risk of atherosclerotic cardiovascular disease.
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Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.
Hamidi, V, Riggs, K, Zhu, L, Bermudez Saint Andre, K, Westby, C, Coverdale, S, Dursteler, A, Wang, H, Miller Iii, C, Taegtmeyer, H, et al
Metabolic syndrome and related disorders. 2020;(5):225-233
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Abstract
Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatide's acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.
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Forearm bone density, cross-sectional size and muscle cross-sectional area in adolescents with diabetes mellitus type 1 assessed by peripheral quantitative computed tomography.
Jaworski, M, Wierzbicka, E, Pludowski, P, Szalecki, M
Journal of musculoskeletal & neuronal interactions. 2019;(4):435-447
Abstract
OBJECTIVES The mechanical components of bone strength (size, shape and density) in adolescents with T1DM are not extensively studied. METHODS The studied group comprises 39 adolescents, aged 11,9-18,0 yrs. The bone and muscle properties were investigated at the forearm (66% and 4% site). All measurements were performed using pQCT method. RESULTS The mean Z-score calculated for the ratio of the total cortical bone cross-sectional area to muscle cross-sectional area at 66% was lower than zero in girls (-0,93+/-1,06; p=0,0042). Significant differences between Tanner stages were noted in boys for mean Z-scores for bone masses, cross-sectional dimensions and strength. CONCLUSIONS T1DM girls revealed a decreased ratio of cortical bone area/muscle area, reflecting disturbed adaptation of the cortical shaft to the muscle force. When the Z-scores of cortical shell dimensions were investigated, cases in Tanner stage 5 diverged from "less mature" individuals, which may suggests that bone shaft development in these individuals was impaired, affecting both size and strength.
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Panitumumab Induced Forearm Panniculitis in Two Women With Metastatic Colon Cancer.
Domenico, C, Antonella, I, Benedetto, C, Luigi, S, Antonio, C, Lidia, C, Giuseppe, S, Gallelli, L
Current drug safety. 2019;(3):233-237
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Abstract
BACKGROUND Panitumumab is an EGFR inhibitor used for the treatment of metastatic colorectal cancer (mCRC), even if its use is related to skin toxicity. CASE PRESENTATION We report the development of forearm panniculitis in two women during the treatment with Panitumumab (6 mg/Kg intravenous every 2 weeks) + FOLFOX-6 (leucovorin, 5- fluorouracil, and oxaliplatin at higher dosage) for the treatment of mCRC. RESULTS In both patients, clinical, laboratory and radiological evaluation documented the presence of a local panniculitis, probably related to panitumumab (Naranjo score: 6). Panatimumab discontinuation and antimicrobial + corticosteroid treatment induced a remission of skin manifestations. CONCLUSION We reported for the first time the development of panniculitis during Panitumumab treatment, and we documented that the treatment with beta-lactams to either fluoroquinolones or oxazolidinone in the presence of corticosteroid improves clinical symptoms in young patients with mCRC, without the development of adverse drug reactions or drug-drug interactions.
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The Utility of DXA Assessment at the Forearm, Proximal Femur, and Lateral Distal Femur, and Vertebral Fracture Assessment in the Pediatric Population: 2019 ISCD Official Position.
Weber, DR, Boyce, A, Gordon, C, Högler, W, Kecskemethy, HH, Misra, M, Swolin-Eide, D, Tebben, P, Ward, LM, Wasserman, H, et al
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2019;(4):567-589
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Dual-energy X-ray absorptiometry (DXA) is widely used in the evaluation of bone fragility in children. Previous recommendations emphasized total body less head and lumbar spine DXA scans for clinical bone health assessment. However, these scan sites may not be possible or optimal for all groups of children with conditions that threaten bone health. The utility of DXA scans of the proximal femur, forearm, and radius were evaluated for adequacy of reference data, precision, ability of predict fracture, and applicability to all, or select groups of children. In addition, the strengths and limitations of vertebral fracture assessment by DXA were evaluated. The new Pediatric Positions provide guidelines on the use of these additional measures in the assessment of skeletal health in children.
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Parathyroid autotransplantation at a novel site for better evaluation of the grafted gland function: study protocol for a prospective, randomized controlled trial.
Cui, Q, Kong, D, Li, Z, Wang, K, Zhang, D, Tang, J, Liao, X, Yuan, Q, Gong, Y, Wu, G
Trials. 2019;(1):96
Abstract
BACKGROUND Hypoparathyroidism is one of the most common complications encountered in thyroidectomy. In addition to parathyroid in-situ preservation, parathyroid autotransplantation (PA) is another important remedial method for patients whose parathyroid glands have been removed. However, an accurate evaluation method for the function of a transplanted parathyroid is lacking. Our preliminary study indicated that patients with PA at novel sites near antecubital veins had higher serum concentrations of parathyroid hormone (PTH). Therefore, the main hypothesis is that a grafted site closer to the cephalic vein is more useful for better evaluation of transplanted parathyroid function. This study aims to confirm the more efficient and accurate evaluation system through a prospective, randomized controlled trial. METHODS In total, 280 patients will be enrolled in this study and randomly divided into two groups: 140 patients with transplanted parathyroid glands in the traditional sites (group A) and the other 140 transplanted in the novel sites (group B), close to the antecubital veins. The serum concentration of PTH and calcium ion from both forearms will be measured and monitored regularly for 12 months. The primary outcome of this trial will be the survival of grafted glands, defined as the ratio of PTH between the grafted vs. the non-grafted forearms being no less than 1.5. The secondary outcome is hypoparathyroidism, defined as the PTH level from the non-grafted forearms being less than 15 pg/ml (normal range 15-65 pg/ml). DISCUSSION Our results from this study should provide a more accurate method to evaluate the function of transplanted parathyroid glands by comparing PTH concentrations in both the grafted and non-grafted forearms following PA at novel sites. A better PTH measurement is helpful not only for the management of postoperative patients, but also for further identification of factors affecting PA success. TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT02906748 . Registered on 16 March 2016.
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The acute influence of sucrose consumption with and without vitamin C co-ingestion on microvascular reactivity in healthy young adults.
West, S, Smail, O, Bond, B
Microvascular research. 2019;:103906
Abstract
BACKGROUND Sugar sweetened beverages (SSB) are a major source of dietary sugar and a public health concern. Glucose consumption acutely influences microvascular reactivity in healthy adults, possibly via oxidative stress. The purpose of this study was to observe the acute influence of a more relevant dose of sucrose on microvascular reactivity, and to identify whether this response is influenced by the amount of vitamin C typically contained in SSB. METHODS Thirteen ostensibly healthy adults (8 male, 5 female) performed three 1-day trials in a randomized order; the consumption of 300 ml water (control; CON), or 300 ml water with 50 g sucrose (SUGAR) or 50 g sucrose with 160 mg of vitamin C (VITC). Near infrared spectroscopy was used to determine peak reactive hyperaemia (PRH), the rate of desaturation (Slope 1) and reperfusion (Slope 2), and the total area under the reperfusion curve versus time (TRH) following 5 min of forearm cuff occlusion before and 30, 60, 90 and 120 min after test drink consumption. RESULTS SUGAR and VITC significantly increased the total area under the curve versus time for plasma glucose (P < 0.05 for both). No changes in microvascular reactivity were observed between trials, although VITC increased Slope 1 compared to both SUGAR and CON 30 and 60 min post drink (P < 0.05 for both). CONCLUSION The consumption of a sugar load representative of commercially available SSB did not influence microvascular reactivity. The co-ingestion of Vitamin C also failed to influence microvascular reactivity, but did increase the rate of oxygen extraction.
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Postexercise Hypotension Is Volume-Dependent in Hypertensives: Autonomic and Forearm Blood Responses.
de Freitas Brito, A, Brasileiro-Santos, MDS, Coutinho de Oliveira, CV, da Cruz Santos, A
Journal of strength and conditioning research. 2019;(1):234-241
Abstract
de Freitas Brito, A, Brasileiro Santos, MdS, Coutinho de Oliveira, CV, and da Cruz Santos, A. Postexercise hypotension is volume-dependent in hypertensives: autonomic and forearm blood responses. J Strength Cond Res 33(1): 234-241, 2019-The purpose of this study was to evaluate the effect of 2 sessions of resistance exercise (RE) with different volumes on postexercise hypotension (PEH), forearm blood flow (FBF), and cardiac autonomic balance (LF/HF) in hypertensive elderly woman. The study was conducted with 16 hypertensive elderly (25.7 ± 3 kg·m², 55.5 ± 3 years) subjected to 3 experimental sessions, i.e., a control session, exercise with a set (S1), and exercise with 3 sets (S3). For each session, the subjects were evaluated before and after intervention. In the preintervention period, blood pressure (BP), FBF, and LF/HF were measured after 10 minutes of rest in the supine position. Thereafter, the subjects were taken to the gym to perform their exercise sessions or remained at rest during the same period. Both S1 and S3 comprised a set of ten repetitions of 10 exercises, with an interval of 90 seconds between exercises. Subsequently, the measurements were again performed at 10, 30, 50, 70, and 90 minutes of recovery (postintervention) in the supine position. Postexercise hypotension (systolic/diastolic) was greater in S3 than in S1 (-26 ± 4/-14 ± 5 mm Hg vs. -18 ± 5/-8 ± 5 mm Hg, p ≤ 0.05). Similarly, FBF and cardiac LF/HF increased in both sessions, being more evident in S3 than in S1 (4.98 ± 0.32 vs. 4.36 ± 0.27 ml·min·100 ml, p ≤ 0.05; and LF/HF = 1.69 ± 0.225 vs. 1.37 ± 0.13 p ≤ 0.05, respectively). We conclude that a single RE session with 3 series were able to promote higher PEH in hypertensive women, and this phenomenon was accompanied by increased FBF and increased cardiac autonomic activity.
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Montmorency cherry supplementation attenuates vascular dysfunction induced by prolonged forearm occlusion in overweight, middle-aged men.
Aboo Bakkar, Z, Fulford, J, Gates, PE, Jackman, SR, Jones, AM, Bond, B, Bowtell, JL
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(1):246-254
Abstract
Flavonoid supplementation improves brachial artery flow-mediated dilation (FMD), but it is not known whether flavonoids protect against vascular dysfunction induced by ischemia-reperfusion (IR) injury and associated respiratory burst. In a randomized, double-blind, placebo-controlled, crossover study, we investigated whether 4 wk supplementation with freeze-dried Montmorency cherry (MC) attenuated suppression of FMD after IR induced by prolonged forearm occlusion. Twelve physically inactive overweight, middle-aged men (52.8 ± 5.8 yr, BMI: 28.1 ± 5.3 kg/m2) consumed MC (235 mg/day anthocyanins) or placebo capsules for 4 wk, with supplementation blocks separated by 4 wk washout. Before and after each supplementation block, FMD responses and plasma nitrate and nitrite ([ NO2- ]) concentrations were measured at baseline and 15, 30, and 45 min after prolonged (20 min) forearm occlusion. FMD response was significantly depressed by the prolonged occlusion ( P < 0.001). After a 45-min reperfusion, FMD was restored to baseline levels after MC (ΔFMD presupplementation: -30.5 ± 8.4%, postsupplementation: -0.6 ± 9.5%) but not placebo supplementation (ΔFMD presupplementation: -11.6 ± 10.6, postsupplementation: -25.4 ± 4.0%; condition × supplement interaction: P = 0.038). Plasma [ NO2- ] decreased after prolonged occlusion but recovered faster after MC compared with placebo (Δ45 min to baseline; MC: presupplementation: -15.3 ± 9.6, postsupplementation: -6.2 ± 8.1; Placebo: presupplementation: -16.3 ± 5.9, postsupplementation: -27.7 ± 11.1 nmol/l; condition × supplement × time interaction: P = 0.033). Plasma peroxiredoxin concentration ([Prx2]) was significantly higher after MC (presupplementation: 22.8 ± 1.4, postsupplementation: 28.0 ± 2.4 ng/ml, P = 0.029) but not after placebo supplementation (presupplementation: 22.1 ± 2.2, postsupplementation: 23.7 ± 1.5 ng/ml). In conclusion, 4 wk MC supplementation enhanced recovery of endothelium-dependent vasodilatation after IR, in parallel with faster recovery of plasma [ NO2- ], suggesting NO dependency. These protective effects seem to be related to increased plasma [Prx2], presumably conferring protection against the respiratory burst during reperfusion. NEW & NOTEWORTHY This is the first study to demonstrate that 4 wk of Montmorency cherry powder supplementation exerted protective effects on endothelium-dependent vasodilation after transient ischemia-reperfusion injury in overweight, physically inactive, nonmedicated, hypertensive middle-aged men. These effects seem to be due to increased nitric oxide availability, as evidenced by higher plasma nitrite concentration and peak arterial diameter during the flow-mediated dilation measurement. This may be a consequence of increased concentration of peroxiredoxin and other antioxidant systems and, hence, reduced reactive oxygen species exposure.