Acute Cardiovascular Adaptation to Strenuous Exercise: An Integrative Ultrasound Study.

OBJECTIVES: The aim of this study was to evaluate the acute effects of participation in an Ironman distance triathlon competition on arterial function by ultrasound, in relation to cardiac function and body water content. METHODS: Twenty-eight male triathletes participating in an Ironman distance competition underwent carotid, femoral, and cardiac ultrasound examinations. Moreover, the presence of extravascular lung water was identified by lung echo B-lines (echogenic coherent wedge-shaped signal with a narrow origin from the hyperechoic pleural line) at rest and within 20 minutes of arrival. RESULTS: At the end of the competition, athletes showed an increased heart rate (mean ± SD, from 60.2 ± 13.1 to 82.8 ± 15.6 beats/min; P < .0001) and unchanged mean blood pressure (from 93 ± 14 to 91 ± 10 mm Hg; P > .05) in the presence of negligible dehydration (total body water from 48.0 ± 4.0 to 46.5 ± 3.9 kg; P > .05). Cardiac output increased (from 5.5 ± 1.2 to 6.7 ± 2.4 L/min; P < .05) in the presence of an unchanged stroke volume (from 64 ± 14 to 59 ± 16 mL; P > .05) and unchanged left ventricular elastance (from 1.52 ± 0.48 to 1.39 ± 0.48 mm Hg/mL/m2 ; P > .05). The mean carotid diameter increased (from 7.19 ± 0.65 to 7.61 ± 0.76 mm; P < .05), whereas the mean femoral diameter was unchanged at the end of the competition (from 10.41 ± 0.83 to 10.49 ± 0.82 mm; P > .05). Carotid intima-media thickness was significantly reduced (from 537 ± 70 to 495 ± 70 µm; P < .05), whereas B-lines increased significantly after the competition (from 1 [0-4] to 12 [5-23]; P < .0001). CONCLUSIONS: These data suggest different acute functional adaptation in central arteries with respect to peripheral leg vessels.

The level of physical training modulates cytokine levels through P2X7 receptor in healthy subjects.

INTRODUCTION: The P2X7 receptor-NLRP3 inflammasome complex (P2X7R-Infl) regulates inflammatory and immune responses. Physical exercise modulates heat-shock proteins (Hsps), influencing cytokine levels and oxidative stress; Hsp72 triggers P2X7R-Infl-dependent responses. SUBJECTS AND METHODS: We studied the effect of a single bout of maximal exercise on lymphomonocyte expression of P2X7R, NLRP3, caspase-1, NF-kB and Hsp72 and circulating levels of IL-1ß, IL-18 and MCP-1, all modulated by P2X7R-Infl, in healthy sedentary (SED), trained (ATH), endurance (END) male individuals. RESULTS: Baseline P2X7R, NLRP3 and Caspase-1 expression progressively increased from SED to ATH and END; NF-kß showed the same trend. Hsp72 did not differ among groups. Acute exercise strongly reduced P2X7R in all participants, irrespective of their degree of physical training. Inflammasome responses differed across groups: in SED, NLRP3 and Caspase-1 increased; in ATH, NLRP3 reduced and caspase-1 did not vary; in END, NLRP3 and Caspase-1 declined. Baseline IL-1ß, higher in END, was unmodified after exercise; IL-18 decreased; MCP-1 doubled in SED, did not vary in ATH, declined in END. In the whole study population, significant direct relationships emerged between P2X7R expression and IL-1ß, IL-18, MCP-1 levels, all P < .001; also Caspase-1 related with these markers. A multivariate analysis showed age, BMI and P2X7R as determinants of postexercise IL-1ß levels. CONCLUSION: Endurance show higher P2X7R-Infl expression and function vs SED and ATH; however, maximal exercise determines prevailing pro-inflammatory vs anti-inflammatory responses in untrained and trained participants, respectively, highlighting a likely cause-effect relationship between degree of physical activity and P2X7R-Infl-mediated responses.

The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers.

OBJECTIVE: Smoking is a recognized cardiovascular risk factor. Perivascular visceral adipose tissue (PVAT) is a source of inflammatory molecules, thus contributing to atherosclerosis progression. The P2X7 receptor (P2X7 R)-inflammasome complex, crucial in determining IL-1ß and IL-18 release, participates in this scenario. We evaluated whether smoking might affect the PVAT inflammatory phenotype and explored the putative role of the axis P2X7 R-inflammasome in this picture. SUBJECTS AND METHODS: TNFα, IL-6, RBP4, MCP-1, as well as P2X7 R and inflammasome components NLRP3, ASC, caspase-1 and IL-1ß and IL-18 expression was determined in adipocytes isolated by PVAT of healthy smokers (Smok) and nonsmokers (No-Smok) subjects. Plasma and culture medium levels of these cytokines were also determined. RESULTS: Perivascular adipose tissue of Smok had a higher expression of P2X7 R and inflammasome components; via P2X7 R activation, it released more IL-1ß and IL-18, whose serum levels were also higher in Smok than in No-Smok. Linear correlations of NLRP3 with P2X7 R and IL-18 expression and release emerged. Smok also had a higher PVAT expression of the chemotactic factor MCP-1. However, no difference was observed in the PVAT expression of genes more strictly related to insulin resistance, like TNFα, RBP4, IL-6; this was coupled with similar plasma levels of TNFα and RBP4 in the two groups. CONCLUSION: Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.

Acute Effects of Triathlon Race on Oxidative Stress Biomarkers.

The response to strenuous exercise was investigated by reactive oxygen species (ROS) production, oxidative damage, thiol redox status, and inflammation assessments in 32 enrolled triathlon athletes (41.9 ± 7.9 yrs) during Ironman® (IR), or half Ironman® (HIR) competition. In biological samples, inflammatory cytokines, aminothiols (glutathione (GSH), homocysteine (Hcy), cysteine (Cys), and cysteinylglycine (CysGly)), creatinine and neopterin, oxidative stress (OxS) biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS)), and ROS were assessed. Thirteen HIR and fourteen IR athletes finished the race. Postrace, ROS (HIR +20%; IR +28%; p < 0.0001), TBARS (HIR +57%; IR +101%), PC (HIR +101%; IR +130%) and urinary neopterin (HIR +19%, IR +27%) significantly (range p < 0.05-0.0001) increased. Moreover, HIR showed an increase in total Cys +28%, while IR showed total aminothiols, Cys, Hcy, CysGly, and GSH increase by +48, +30, +58, and +158%, respectively (range p < 0.05-0.0001). ROS production was significantly correlated with TBARS and PC (R 2 = 0.38 and R 2 = 0.40; p < 0.0001) and aminothiols levels (range R 2 = 0.17-0.47; range p < 0.01-0.0001). In particular, ROS was directly correlated with the athletes' age (R 2 = 0.19; p < 0.05), with ultraendurance years of training (R 2 = 0.18; p < 0.05) and the days/week training activity (R 2 = 0.16; p < 0.05). Finally, the days/week training activity (hours/in the last 2 weeks) was found inversely correlated with the IL-6 postrace (R 2 = -0.21; p < 0.01). A strenuous performance, the Ironman® distance triathlon competition, alters the oxidant/antioxidant balance through a great OxS response that is directly correlated to the inflammatory parameters; furthermore, the obtained data suggest that an appropriate training time has to be selected in order to achieve the lowest ROS production and IL-6 concentration at the same time.

Syphilis iridocyclitis in a patient with type 1 diabetes.

We present a rare cause of iridocyclitis in a patient with vitiligo and type 1 diabetes who showed poor metabolic control, and suffered from remitting fever, weight loss, fatigue, diffuse arthralgias and reduced visual acuity. Mild systemic symptoms coupled with increased cholestasis enzymes, insulin resistance, mild inflammation and a functioning adrenal gland focused our clinical work-up on granulomatous causes of iridocyclitis. Specific tests confirmed syphilis, with no involvement of the central nervous system. Ocular syphilis, despite being unusual, can be the only manifestation of the disease. The work-up of any unexplained ocular inflammation should include testing for syphilis so as to not delay the diagnosis.

Glucose Metabolism in High-Risk Subjects for Type 2 Diabetes Carrying the rs7903146 TCF7L2 Gene Variant.

CONTEXT: The mechanisms responsible for contribution of variants in the gene TFC7L2 to the risk for type 2 diabetes (T2DM) remains far from being completely understood, and available studies have generated nonunivocal results. OBJECTIVE: We investigated the postprandial glucose metabolism in subjects at risk for T2DM carrying the TCF7L2 risk allele. DESIGN, SETTING, AND PARTICIPANTS: Twenty-three subjects carrying the risk-conferring TCF7L2 genotypes (11 TT and 12 CT at rs7901346) and 13 subjects with wild-type genotype (CC) underwent a standard mixed-meal test (MMT) in combination with stable isotope tracers. OUTCOME MEASUREMENTS: We evaluated endogenous and exogenous glucose fluxes and hormonal responses. RESULTS: Fasting plasma glucose, insulin, C-peptide, glycated hemoglobin, endogenous glucose production, and plasma glucose clearance were similar in the three groups, whereas plasma glucagon levels were lower in both CT and TT than in CC (64 ± 20, 63 ± 18 and 90 ± 29 pg/mL, respectively; both P = .01). In response to the MMT, TT subjects had lower plasma glucose levels than CC subjects [mean area under the time-concentration curve (AUC) 6.1 ± 3.9 vs 7.1 ± 12.0 mmol/L, P = .04] and lower insulin secretion rate (mean AUC 385 ± 95 vs 530 ± 159 pmol/m(2) · min, P = .02). Initial (0-60 min) rate of appearance (Ra) of oral glucose was lower in TT compared with CT/CC (AUC 2.7 ± 1.1 vs 3.8 ± 1.2 µmol/kg · min, P = .02) with no difference among the three groups in endogenous glucose production. The AUC0-60min for Ra of exogenous glucose (Raex) was positively correlated with the plasma glucose AUC0-60min. Total Raex AUC0-120min was correlated with total AUC0-120min of plasma glucose (r = 0.45, P < .01). Plasma glucagon-like peptide-1 and glucose-dependent insulinotropic peptide levels in response to the MMT were not affected by genotype. CONCLUSIONS: In subjects at risk for T2DM, the TCF7L2 polymorphisms were associated with reduced Raex into systemic circulation, causing reduced postprandial blood glucose increase and, in turn, lower insulin secretion rate with no impairment in ß-cell function. The reduced Raex is likely due to greater glucose retention in the splanchnic area.

A "Google Image" diagnosis of Madelung's disease.

Given the rare nature of Madelung's disease many clinicians will not have seen a patient with it and will not be able to recognise them: subsequently a diagnosis is unlikely to be made.