Antonio Colantuoni

Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta-analysis

High adiposity in middle age is associated with higher dementia risk. The association between weight loss and cognitive function in older adults is still controversial. A meta‐analysis was undertaken to estimate the effectiveness of intentional weight loss on cognitive function in overweight and obese adults. A structured strategy was used to search randomized and non‐randomized studies reporting the effect of intentional and significant weight loss on cognitive function in overweight and obese subjects. Information on study design, age, nutritional status, weight‐loss strategy, weight lost and cognitive testing was extracted. A random‐effect meta‐analysis was conducted to obtain summary effect estimates for memory and attention–executive domains. Twelve studies met inclusion criteria. Seven were randomized trials and the remaining five included a control group. A low‐order significant effect was found for an improvement in cognitive performance with weight loss in memory (effect size 0.13, 95% CI 0.00–0.26, P = 0.04) and attention/executive functioning (effect size 0.14, 95% CI 0.01–0.27, P < 0.001). Studies were heterogeneous in study design, sample selection, weight‐loss intervention and assessment of cognitive function. Weight loss appears to be associated with low‐order improvements in executive/attention functioning and memory in obese but not in overweight individuals.

Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury

The liver is susceptible to such oxidative and metabolic stresses as ischemia-reperfusion (I/R) and fatty acid accumulation. Probiotics are viable microorganisms that restore the gut microbiota and exert a beneficial effect on the liver by inhibiting bacterial enzymes, stimulating immunity, and protecting intestinal permeability. We evaluated Lactobacillus paracasei F19 (LP-F19), for its potential protective effect, in an experimental model of I/R (30 min ischemia and 60 min reperfusion) in rats fed a standard diet or a steatogen [methionine/choline-deficient (MCD)] diet. Both groups consisted of 7 sham-operated rats, 10 rats that underwent I/R, and 10 that underwent I/R plus 8 wk of probiotic dietary supplementation. In rats fed a standard diet, I/R induced a decrease in sinusoid perfusion (P < 0.001), severe liver inflammation, and necrosis besides an increase of tissue levels of malondialdehyde (P < 0.001), tumor necrosis factor-alpha (P < 0.001), interleukin (IL)-1beta (P < 0.001), and IL-6 (P < 0.001) and of serum levels of transaminase (P < 0.001) and lipopolysaccharides (P < 0.001) vs. sham-operated rats. I/R also induced a decrease in Bacterioides, Bifidobacterium, and Lactobacillus spps (P < 0.01, P < 0.001, and P < 0.001, respectively) and an increase in Enterococcus and Enterobacteriaceae (P < 0.01 and P < 0.001, respectively) on intestinal mucosa. The severity of liver and gut microbiota alterations induced by I/R was even greater in rats with liver inflammation and steatosis, i.e., MCD-fed animals. LP-F19 supplementation significantly reduced the harmful effects of I/R on the liver and on gut microbiota in both groups of rats, although the effect was slightly less in MCD-fed animals. In conclusion, LP-F19 supplementation, by restoring gut microbiota, attenuated I/R-related liver injury, particularly in the absence of steatosis.

Geometric Characteristics of Arterial Network of Rat Pial Microcirculation

Objective: The aim of the study was to assess the geometric characteristics of rat pial microcirculation and describe the vessel bifurcation patterns by ‘connectivity matrix’. Methods: Male Wistar rats were used to visualize pial microcirculation by a fluorescent microscopy technique through an open cranial window, using fluorescein isothiocyanate bound to dextran (molecular weight 70 kDa). The arteriolar network was mapped by stop-frame images. Diameters and lengths of arterioles were measured with a computer-assisted method. Pial arterioles were classified according to a centripetal ordering scheme (Strahler method modified according to diameter) from the smallest order 1 to the largest order 5 arterioles in the preparation. A distinction between arteriolar segments and elements was used to express the series-parallel features of the pial arteriolar networks. A connectivity matrix was used to describe the connection of blood vessels from one order to another. Results: The arterioles were assigned 5 orders of branching by Strahler’s ordering scheme, from order 1 (diameter: 16.0 ± 2.5 µm) to order 5 (62 ± 5.0 µm). Order 1 arterioles gave origin to capillaries, assigned order 0. The diameter, length and branching of the 5 arteriolar orders grew as a geometric sequence with the order number in accordance with Horton’s law. The segments/elements ratio was the highest in order 4 and 3 arterioles, indicating the greatest asymmetry of ramifications. Finally, the branching vessels in the networks were described in details by the connectivity matrix. Fractal dimensions of arteriolar length and diameter were 1.75 and 1.78, respectively. Conclusions: The geometric characteristics of rat pial microcirculation indicate that distribution of vessels is fractal. The connectivity matrix allowed us to describe the number of daughter vessels spreading from parent vessels. This ordering scheme may be useful to describe vessel function, according to diameter, length and branching.

Remodeling of Cerebral Microcirculation after Ischemia-Reperfusion.

Clinical and experimental studies have been focused on the pathophysiological mechanisms induced by brain ischemia-reperfusion injury. Recovery events, such as neurogenesis, angiogenesis and the growth of new blood vessels from the preexisting vascular tree, have been intensively studied in the last decades to clarify the vascular remodeling crucial for stroke outcome. This review aims to discuss the cerebral microcirculation remodeling induced by ischemia-reperfusion and the mechanisms involved in angiogenesis and vasculogenesis. The first in vivo observations were focused on anastomotic shunting of cerebral blood flow (CBF) in experimental and clinical models. Thereafter, vascular remodeling induced by cerebral ischemia-reperfusion was reported in mice and rats. Successively, other studies have assessed that within 30 days of middle cerebral artery (MCA) occlusion in rats, there is an increase in CBF and recovery from stroke. Recently, rats submitted to transient MCA occlusion showed pial microcirculation remodeling with the formation of new arterioles sprouting from penumbra vessels and overlapping the ischemic core. This review focuses on the production and/or activation of vasculotrophic factors able to trigger and facilitate microvascular remodeling. Vascular endothelial growth factor and endothelium-released nitric oxide appear to be the main factors involved in the formation of new vessels during microvascular remodeling. These studies are fundamental for consequent interventions on molecular targets, useful for fostering vascular remodeling and the recovery of functions.

Aggregate predictions improve accuracy when calculating metabolic variables used to guide treatment

BACKGROUND Many components of clinical management are tailored to metabolic variables, such as fat-free mass, fat mass, resting metabolic rate (RMR), and body surface area. However, these traits are difficult to measure in routine care and are typically predicted from simple anthropometric or bedside body-composition measurements. Many prediction equations have been published, but validation studies have shown that these equations tend to have limited accuracy in individuals and many have significant average bias. OBJECTIVE We tested a mathematical approach that assumes that the aggregate of many independent predictions is more accurate than the best single prediction. DESIGN Body composition was measured in 196 children aged 4-16 y by using the 4-component model. RMR was measured in 142 adult women. Data on weight, height, age, skinfold thickness, and body impedance were used in published equations to predict body composition (12 equations) or RMR (13 equations). The accuracy of individual compared with aggregate predictions, relative to the reference measurements, was compared by using the Bland and Altman method. RESULTS For childrens body composition and adult RMR, the aggregate predictions had lower mean biases and lower limits of agreement than did the individual predictions, and the aggregate predictions performed better than did any individual prediction. CONCLUSIONS Aggregate predictions perform better than single predictions at predicting fat-free mass, fat mass, total body water, and RMR. Our findings indicate that the accuracy of calculating variables such as energy requirements and drug and dialysis dosages can be improved significantly with the use of our mathematical approach.

NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis

Blood pressure homeostasis is maintained by several mechanisms regulating cardiac output, vascular resistances, and blood volume. At cellular levels, reactive oxygen species (ROS) signaling is involved in multiple molecular mechanisms controlling blood pressure. Among ROS producing systems, NADPH oxidases (NOXs), expressed in different cells of the cardiovascular system, are the most important enzymes clearly linked to the development of hypertension. NOXs exert a central role in cardiac mechanosensing, endothelium-dependent relaxation, and Angiotensin-II (Ang-II) redox signaling regulating vascular tone. The central role of NOXs in redox-dependent cardiovascular cell functions renders these enzymes a promising pharmacological target for the treatment of cardiovascular diseases, including hypertension. The aim of the present review is to focus on the physiological role of the cardiovascular NOX-generating ROS in the molecular and cellular mechanisms affecting blood pressure.

Protective Effects of Quercetin on Rat Pial Microvascular Changes during Transient Bilateral Common Carotid Artery Occlusion and Reperfusion

The aim of this study was to assess the in vivo effects of quercetin on pial microvascular responses during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified in five orders of branchings. Capillaries were assigned order 0, the smallest arterioles order 1, and the largest ones order 5. In ischemic rats, 30 min BCCAO and 60 min reperfusion caused arteriolar diameter decrease (by 14.5 ± 3.3% of baseline in order 2), microvascular leakage [0.47 ± 0.04, normalized gray levels (NGL)], leukocyte adhesion in venules (9 ± 2/100 μm venular length, v.l./30 s), and reduction of capillary perfusion (by 40 ± 7% of baseline). Moreover, at the end of BCCAO and reperfusion there was a significant increase in reactive oxygen species (ROS) formation when compared with baseline. Quercetin highest dose determined dilation in all arteriolar orders (by 40 ± 4% of baseline in order 2) and prevented microvascular permeability (0.15 ± 0.02 NGL), leukocyte adhesion (3 ± 1/100 μm v.l./30 s) as well as ROS formation, while capillary perfusion was protected. Inhibition of endothelial nitric oxide synthase (NOS) prior to quercetin reduced arteriolar dilation (order 2 diameter increase by 10.3 ± 2.5% of baseline) and caused permeability increase (0.29 ± 0.03 NGL); inhibition of neuronal NOS or inducible NOS did not affect quercetin-induced effects. Inhibition of guanylyl cyclase prior to quercetin reversed the quercetin’s effects on pial arteriolar diameter and leakage. In conclusion, quercetin was able to protect pial microcirculation from ischemia–reperfusion damage inducing arteriolar dilation likely by nitric oxide release. Moreover, quercetin scavenger activity blunted ROS formation preserving the blood–brain barrier integrity.

Protective effects of insulin during ischemia-reperfusion injury in hamster cheek pouch microcirculation.

Objective: The effects of insulin (0.18 nM–0.18 µM) on reduced capillary perfusion, microvascular permeability increase and leukocyte adhesion induced by ischemia-reperfusion injury were investigated in the hamster cheek pouch microcirculation. To gain insight into the insulin’s mechanism of action, the effects of its higher concentration (0.18 µM) were investigated after inhibition of tyrosine kinase (TK), nitric oxide synthase (NOS), protein kinase C (PKC), phosphatidylinositol 3-kinase and K+(ATP) channels, alone or in combination. Two concentrations for each inhibitor were used. Methods: Microcirculation was visualized by fluorescence microscopy. Perfused capillary length, microvascular permeability, leukocyte adhesion to venular walls, vessel diameter and capillary red blood cell velocity were assessed by computer-assisted methods. Measurements were made at baseline (B), after 30 min of ischemia (I), and after 30 min of reperfusion (R). Results: In control animals, perfused capillary length decreased by 63 ± 5% of baseline at R. Microvascular permeability increased at I and R, while leukocyte adhesion was most pronounced in V1 postcapillary venules at R. Insulin dose-dependently preserved capillary perfusion at R (–28 ± 6 and –15 ± 6% of baseline), but was unable to prevent the increase in permeability at I (0.25 ± 0.05 and 0.29 ± 0.06 Normalized Grey Levels, NGL) and R (0.49 ± 0.10 and 0.53 ± 0.09 NGL), according to the concentrations. Adhesion of leukocytes was observed mostly in V3 venules at R (9 ± 2 and 10 ± 2/100 µm venular length, with the lower and higher concentration, respectively). Nitric oxide synthase inhibition by NG-nitro-L-arginine-methyl ester prior to insulin did not affect capillary perfusion at R (–18 ± 3% of baseline with higher concentration), but prevented permeability increase (0.20 ± 0.04 NGL, according to higher concentration) and reduced leukocyte adhesion in V3 venules at R (1.5 ± 1.0/100 µm of venular length, with higher concentration). Blockade of K+(ATP) channels by glibenclamide prior to insulin decreased perfused capillary length at R (–58 ± 6% of baseline with higher concentration), attenuated leakage at R (0.30 ± 0.04 NGL, according to higher concentration) and caused leukocyte adhesion mainly in V1 venules at R (9.0 ± 1.5/100 µm of venular length, with higher concentration). Inhibition of either TK, PKC or phosphatidylinositol 3-kinase did not affect microvascular responses to insulin. Simultaneous inhibition of TK and NOS did not increase protection. Conclusions: Insulin prevents ischemia-reperfusion injury by promoting capillary perfusion through an apparent activation of K+(ATP) channels and increase in nitric oxide release.

Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion: Effects of Hypertonic Glycerol

Objective: The aim of the study was to assess the rat pial microvessel alterations due to transient bilateral common carotid artery occlusion (BCCAO) and to investigate the mechanism of 10% hypertonic glycerol neuroprotection. Our suggestion was that 10% glycerol solution infusion could dilate pial arterioles through nitric oxide release and/or stimulation of ATP-sensitive potassium (KATP) channels. Therefore, we studied the effects of hypertonic glycerol after inhibition of nitric oxide synthase, with NG-nitro-L-arginine-methyl ester or NG-nitro-L-arginine, or KATP channels with glibenclamide. Methods: Pial microcirculation of male Wistar rats was visualized by a fluorescent microscopy technique through an open cranial window, using fluorescein isothiocyanate bound to dextran (molecular weight 70 kDa). BCCAO was induced for 30 min and reperfusion lasted 60 min. The arterioles were classified according to the Strahler ordering scheme. Permeability increase was quantified by normalized grey levels (NGL). Leucocytes were stained with rhodamine 6G. Perfused capillary length and capillary red blood cell (RBC) velocity were measured by computer-assisted methods. Results: The arterioles were assigned 5 orders of branchings, from order 1 (diameter 16.0 ± 2.5 µm) to order 5 (62.0 ± 5.0 µm). BCCAO caused inhomogenous changes in diameter of arterioles and leakage of fluorescent dextran, that was further enhanced by reperfusion (0.45 ± 0.05 NGL, p < 0.01). Adhesion of leukocytes to venules was marked and capillary perfusion was reduced by 39.2 ± 6.0% of baseline as well as capillary RBC velocity. 10% glycerol solution caused an increase in diameter of all arterioles within 25 ± 2 min of administration (by 20 ± 5% in order 4, 25 ± 4% in order 3 and 18 ± 3% in order 2; p < 0.01). Leakage (0.19 ± 0.03 NGL, p < 0.01), leukocyte adhesion (2.0 ± 1.0/100 µm of venular length, p < 0.01) and capillary occlusion (reduction by 13.0 ± 5.5% of baseline) were prevented compared with controls. Capillary RBC velocity increased compared with controls. NG-nitro-L-arginine-methyl ester or NG-nitro-L-arginine infused prior to glycerol caused vasoconstriction and reduced the protective effects of hypertonic glycerol on permeability increase. The number of adherent leukocytes and perfused capillary length decreased, while capillary RBC velocity was higher than baseline. Glibenclamide prior to 10% glycerol solution blunted glycerol-induced vasodilatation, but did not affect protection by hypertonic glycerol on blood-brain barrier disruption, leukocyte adhesion and capillary perfusion, preserving high capillary RBC velocity. Papaverine (20 mg/kg body weight) induced an increase in arteriolar diameter, enhancing interstitial edema; adhesion of leukocytes was marked as well as capillary occlusion, while capillary RBC velocity increased. Conclusions: 10% glycerol solution was able to prevent microvascular alterations due to BCCAO protecting cerebral tissue. The effects appear to be due to hyperosmolality causing stimulation of KATP channels, increase in vessel wall shear stress and release of nitric oxide.

Weight loss expectations and body dissatisfaction in young women attempting to lose weight

BACKGROUND Unrealistic weight loss expectations (WLEs) and greater body dissatisfaction may be associated with the poor long-term outcomes of dietary and lifestyle weight loss treatments. We evaluated the association between body size, WLEs and body dissatisfaction in young women attempting to lose weight. METHODS Forty-four young healthy women [age range 18-35 years, body mass index (BMI) range 23-40 kg/m2] were recruited. Women were classified as obese (BMI ≥ 30.0 kg/m2) and non-obese (BMI <30.0 kg/m2). The Body Dissatisfaction scale of the Eating Disorder Inventory-2 and the Body Image Assessment for Obesity silhouette charts were used to assess body dissatisfaction. WLEs were categorised according to personal (ideal, happiness, satisfaction, weight history), lifestyle (fitness) and social (career, family acceptance, peer acceptance, mass media, social pressure) factors. Individual WLEs were compared with recommended clinical targets (5%, 10% and 20%) for weight loss. RESULTS Body dissatisfaction was lower in non-obese subjects and was directly associated with BMI (P < 0.05). WLEs were directly associated with BMI and the obese group reported greater expectations. Five non-obese subjects (23%) desired to lose more than 20% of their body weight, whereas the proportion was significantly higher in the obese group (17 subjects; 74%). Subjects derived the greatest WLEs from mass media, whereas they perceived that family and friends were supportive of a lesser degree of weight loss. CONCLUSIONS We observed a mismatch between clinical and personal expectations, and social pressure and interpersonal relationships appear to have a prominent role with respect to influencing the association.