Obesity blunts cephalic-phase microvascular responses to food.

Neurally mediated anticipatory responses, also named cephalic-phase responses, and microcirculatory regulation are two important mechanisms to maintain metabolic homeostasis. Altered cephalic-phase responses in obesity and its metabolic consequences have been proposed. There is, however, a lack of studies focusing on in vivo assessment of the microcirculation during this phase in patients with obesity. In this randomized controlled trial, we selected patients with obesity and healthy subjects after clinical and laboratory assessments. Those with obesity were randomized into two groups: experimental (cephalic-phase microvascular response stimulation - CP group, n = 13) and controls (n = 14). Healthy subjects (n = 17) were also included to form a CP control group. Skin microvascular assessment was used as a model of systemic microcirculation. Resting functional capillary density (FCD) and peak FCD during post-occlusive reactive hyperemia (PORH) were measured by dorsal finger videocapillaroscopy and expressed mainly capillary recruitment capacity. Resting red blood cell velocity (RBCV), peak RBCV during PORH (RBCVmax), and time taken to reach RBCVmax (TRBCVmax) were assessed by dynamic nailfold videocapillaroscopy and expressed the microhemodynamics. Patients with obesity (with or without stimulus) failed to show an increase on FCD during PORH post-stimulus (p = 0.221 and p = 0.307, respectively) depicting lack of capillary recruitment. In contrast, healthy subjects presented an increase in this microvascular outcome (p = 0.004). Changes in all variables of microhemodynamics occurred in both CP groups (healthy and those with obesity). During CP, we originally demonstrated an absence of capillary recruitment in subjects with obesity. These findings might contribute to the literature of microvascular impairment and metabolic conditions.

Clinical and laboratory markers associated with anti-TNF-alpha trough levels and anti-drug antibodies in patients with inflammatory bowel diseases.

Monitoring anti-TNF agents in inflammatory bowel disease (IBD) patients may be helpful in optimizing outcomes. We aimed to evaluate potential correlations among demographic, clinical, laboratory, or imaging parameters, as well as serum levels of infliximab (IFX) and adalimumab (ADA) and their respective antibodies, in the clinical management of IBD patients.A cross-sectional study of 95 patients with Crohn's disease (CD) or ulcerative colitis (UC) in maintenance therapy with infliximab or adalimumab was performed. Drug trough levels and anti-drug levels were determined using ELISA-based assays.Regarding the serum IFX dosage, patients with higher relative C-reactive protein (CRP) levels had significantly lower relative serum IFX levels (<3 µg/mL) (P = .028). In contrast, higher concentrations of anti-IFX antibodies were found in patients who were not on concomitant immunomodulators (P = .022) and who had more biological-related adverse events (P = .001) and higher levels of CRP (P = .042). Serum CRP levels were also negatively correlated with IFX (CC = -0.315; P = .033) but positively correlated with the presence of IFX antibodies (CC = 0.327; P = .027). Serum albumin dosage showed a positive correlation with levels of both IFX (CC = 0.379; P = .004) and ADA (CC = 0.699; P = .003).Although anti-TNF-α trough levels and immunogenicity do not show a significant correlation with disease outcome, our results reinforce the use of combination therapy for patients treated with infliximab. Moreover, we confirmed the presence of significant associations between anti-TNF-α trough levels and immunogenicity with body mass index (BMI), the concomitant use of immunomodulators, the rates of side effects, and laboratory markers, including serum albumin and CRP.

Effects of babassu nut oil on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in the microcirculation: observation in the hamster cheek pouch.

BACKGROUND: The babassu palm tree is native to Brazil and is most densely distributed in the Cocais region of the state of Maranhão, in northeastern Brazil. In addition to the industrial use of refined babassu oil, the milk, the unrefined oil and the nuts in natura are used by families from several communities of African descendants as one of the principal sources of food energy. The objective of this study was to evaluate the effects of babassu oil on microvascular permeability and leukocyte-endothelial interactions induced by ischemia/reperfusion using the hamster cheek pouch microcirculation as experimental model. METHODS: Twice a day for 14 days, male hamsters received unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18 ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations were made in the cheek pouch and macromolecular permeability increase induced by ischemia/reperfusion (I/R) or topical application of histamine, as well as leukocyte-endothelial interaction after I/R were evaluated. RESULTS: The mean value of I/R-induced microvascular leakage, determined during reperfusion, was significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001). In addition, histamine-induced increase of microvascular permeability was significantly less pronounced in BO groups compared to MO one. No significant differences among groups in terms of leukocyte adhesion, concentrations of tumor necrosis factor alpha, interleukin 1, and interleukin 6 were found. CONCLUSIONS: Our findings suggest that unrefined babassu oil reduced microvascular leakage and protected against histamine-induced effects in postcapillary venules and highlights that these almost unexploited nut and its oil might be secure sources of food energy.

Novel findings in the cephalic phase of digestion: a role for microcirculation?

The cephalic phase of digestion (CPD) has been extensively investigated in terms of digestion and metabolism. Nevertheless, microcirculatory changes required to prepare peripheral tissues in order to dispose nutrients have never been assessed. In this study, microvascular function has been evaluated to determine its behavior and potential association to hormonal secretions during CPD. Thirty-nine healthy male subjects, 23.4 ± 0.5 years (mean ± SD) and BMI of 23.3 ± 2.3 kg/m(2), were randomized into receiving cognitive-sensorial stimuli to elicit CPD (CPD group, n=20) or not (control group, n=19), after a 12-h overnight fast. Main outcomes were differences in resting and peak functional capillary density (FCD, cap/mm(2)); resting red blood cell velocity (RBCV), peak RBCV (RBCV(max)) and time taken to reach it (TRBCV(max)); peak flow and vasomotion, before and after CPD and their associations with insulin and/or pancreatic polypeptide (PP). In the CPD group, basal FCD (24.9 ± 7.6 to 28.3 ± 8.1, p=0.005), peak FCD (27.8 ± 6.3 to 32.6 ± 7.1, p=0.002), RBCV (0.306 ± 0.031 to 0.330 ± 0.027 mm/s, p=0.005), RBCV(max) (0.336 ± 0.029 to 0.398 ± 0.292 mm/s, p=0.005) and peak flow (23.5 ± 14.3 to 26.9 ± 15.8 PU, p<0.01) increased while TRBCV(max) decreased (4.9 ± 1.5 to 3.5 ± 1.2s, p=0.01). No significant changes could be detected in the control group. Groups have not presented differences for insulin, but PP significantly increased in the CPD group and was positively associated to basal FCD increase (rho=0.527, p=0.03). In conclusion, neurally-mediated anticipatory responses of digestion elicited functional capillary recruitment associated to PP in healthy men, suggesting a precocious role for microcirculation in the physiology of digestion and nutrient homeostasis.