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Espedita Muscariello,1 Gilda Nasti,1 Mario Siervo,2 Martina Di Maro,1 Dominga Lapi,1 Gianni D’Addio,3 Antonio Colantuoni1 1Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy; 2Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK; 3IRCCS Salvatore Maugeri Foundation, Telese, Italy Objective: To determine the prevalence of sarcopenia in a population of obese older women and to assess the effect of a diet moderately rich in proteins on lean mass in sarcopenic obese older women. Materials and methods: A total of 1,030 females, >65 years old, body mass index >30 kg/m2, were investigated about their nutritional status. Muscle mass (MM) was estimated according to the Janssen equation (MM =0.401× height2/resistance measured at 50 kHz +3.825× sex -0.071× age +5.102). Sarcopenia was defined according to the MM index, MM/height2 (kg/m2), as two standard deviations lower than the obesity-derived cutoff score (7.3 kg/m2). A food-frequency questionnaire was used to measure participants’ usual food intake during the previous 3 months. Moreover, a group of sarcopenic obese older women (n=104) was divided in two subgroups: the first (normal protein intake [NPI], n=50) administered with a hypocaloric diet (0.8 g/kg desirable body weight/day of proteins), and the second treated with a hypocaloric diet containing 1.2 g/kg desirable body weight/day of proteins (high protein intake [HPI], n=54), for 3 months. Dietary ingestion was estimated according to a daily food diary, self-administered, and three reports of nonconsecutive 24-hour recall every month during the follow-up. Results: The 104 women were classified as sarcopenic. After dieting, significant reductions in body mass index were detected (NPI 30.7±1.3 vs 32.0±2.3 kg/m2, HPI 30.26±0.90 vs 31.05±2.90 kg/m2; P

The mechanical and biological behaviors of PMMA/Al 2 O 3 composites incorporating 30 wt.%, 40 wt.%, and 50 wt.% of Al 2 O 3 were thoroughly characterized as regards to their possible application in implant-supported prostheses. The Al 2 O 3 particles accounted for an increase in the flexural modulus of PMMA. The highest value was recorded for the composite containing 40 wt.% Al 2 O 3 (4.50 GPa), which was about 18% higher than that of its unfilled counterpart (3.86 GPa). The Al 2 O 3 particles caused a decrease in the flexural strength of the composites, due to the presence of filler aggregates and voids, though it was still satisfactory for the intended application. The roughness (Ra) and water contact angle had the same trend, ranging from 1.94 µm and 77.2° for unfilled PMMA to 2.45 µm and 105.8° for the composite containing the highest alumina loading, respectively, hence influencing both the protein adsorption and cell adhesion. No cytotoxic effects were found, confirming that all the specimens are biocompatible and capable of sustaining cell growth and proliferation, without remarkable differences at 24 and 48 h. Finally, Al 2 O 3 was able to cause strong cell responses (cell orientation), thus guiding the tissue formation in contact with the composite itself and not enhancing its osteoconductive properties, supporting the PMMA composite's usage in the envisaged application.

In this work, the combination of biochar produced through a pyrolytic process of hemp hurd with commercial humic acid as a potential biomass-based flame-retardant system for ethylene vinyl acetate copolymer is thoroughly investigated. To this aim, ethylene vinyl acetate composites containing hemp-derived biochar at two different concentrations (i.e., 20 and 40 wt.%) and 10 wt.% of humic acid were prepared. The presence of increasing biochar loadings in ethylene vinyl acetate accounted for an increasing thermal and thermo-oxidative stability of the copolymer; conversely, the acidic character of humic acid anticipated the degradation of the copolymer matrix, even in the presence of the biochar. Further, as assessed by forced-combustion tests, the incorporation of humic acid only in ethylene vinyl acetate slightly decreased both peaks of heat release rate (pkHRR) and total heat release (THR, by 16% and 5%, respectively), with no effect on the burning time. At variance, for the composites containing biochar, a strong decrease in pkHRR and THR values was observed, approaching -69 and -29%, respectively, in the presence of the highest filler loading, notwithstanding, for this latter, a significant increase in the burning time (by about 50 s). Finally, the presence of humic acid significantly lowered the Young's modulus, unlike biochar, for which the stiffness remarkably increased from 57 MPa (unfilled ethylene vinyl acetate) to 155 Mpa (for the composite containing 40 wt.% of the filler).

To reduce the use of carbon components sourced from fossil fuels, hemp fibers were pyrolyzed and utilized as filler to prepare EVA-based composites for automotive applications. The mechanical, tribological, electrical (DC and AC) and thermal properties of EVA/fiber biochar (HFB) composites containing different amounts of fibers (ranging from 5 to 40 wt.%) have been thoroughly studied. The morphological analysis highlighted an uneven dispersion of the filler within the polymer matrix, with poor interfacial adhesion. The presence of biochar fibers did not affect the thermal behavior of EVA (no significant changes of Tm, Tc and Tg were observed), notwithstanding a slight increase in the crystallinity degree, especially for EVA/HFB 90/10 and 80/20. Conversely, biochar fibers enhanced the thermo-oxidative stability of the composites, which increased with increasing the biochar content. EVA/HFB composites showed higher stiffness and lower ductility than neat EVA. In addition, high concentrations of fiber biochar allowed achieving higher thermal conductivity and microwave electrical conductivity. In particular, EVA/HFB 60/40 showed a thermal conductivity higher than that of neat EVA (respectively, 0.40 vs. 0.33 W·m -1 ·K -1 ); the same composite exhibited an up to twenty-fold increased microwave conductivity. Finally, the combination of stiffness, enhanced thermal conductivity and intrinsic lubricating features of the filler resulted in excellent wear resistance and friction reduction in comparison with unfilled EVA.

Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion-reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood-brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT 1 R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion-reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion-reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT 1 R or MAS receptors able to affect cerebral microvascular injury.

The surface functionalisation of high-density polyethylene (HDPE) and HDPE/alumina-toughened zirconia (ATZ) surfaces with chitosan via electron-beam (EB) irradiation technique was exploited for preparing materials suitable for biomedical purposes. ATR-FTIR analysis and wettability measurements were employed for monitoring the surface changes after both irradiation and chitosan grafting reaction. Interestingly, the presence of ATZ loadings beyond 2 wt% influenced both the EB irradiation process and the chitosan functionalisation reaction, decreasing the oxidation of the surface and the chitosan grafting. The EB irradiation induced an increase in Young's modulus and a decrease in the elongation at the break of all analysed systems, whereas the tensile strength was not affected in a relevant way. Biological assays indicated that electrostatic interactions between the negative charges of the surface of cell membranes and the -NH 3 + sites on chitosan chains promoted cell adhesion, while some oxidised species produced during the irradiation process are thought to cause a detrimental effect on the cell viability.

Background: Several studies indicate that hypertension causes major changes in the structure of the vessel wall by affecting the regulation of blood supply to the tissues. Recently, it has been observed that capillary blood flow is also considerably influenced by the structural arrangement of the microvascular networks that undergo rarefaction (reduction of the perfused vessel number). Therefore, this study aimed to assess the geometric arrangements of the pial arteriolar networks and the arteriolar rhythmic diameter changes in spontaneously hypertensive rats (SHRs)., Methods: Fluorescence microscopy was utilized to observe in vivo the pial microcirculation through a closed cranial window. Pial arterioles were classified according to Strahler's method. The arteriolar rhythmic diameter changes were evaluated by a generalization short-time Fourier transform., Result: Young SHRs showed four orders of vessels while the adult ones only three orders. The diameter, length, and branching number obeyed Horton's law; therefore, the vessels were distributed in a fractal manner. Larger arterioles showed more asymmetrical branches than did the smaller ones in young SHRs, while in adult SHRs smaller vessels presented asymmetrical branchings. In adult SHRs, there was a significant reduction in the cross-sectional area compared with the young SHRs: this implies an increase in peripheral resistance. Young and adult age-matched normotensive rats did not show significant alterations in the geometric arteriolar arrangement with advancing age, both had four orders of arteriolar vessels, and the peripheral resistance did not change significantly. Conversely, the frequency components evaluated in arteriolar rhythmic diameter changes of young and adult SHRs showed significant differences because of a reduction in the frequency components related to endothelial activity detected in adult SHRs., Conclusion: In conclusion, hypertension progressively causes changes in the microarchitecture of the arteriolar networks with a smaller number of vessels and consequent reduced conductivity, characteristic of rarefaction. This was accompanied by a reduction in the formation and release of independent and dependent - endothelial nitric oxide components regulating arterial vasomotion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lapi, Di Maro, Serao, Chiurazzi, Varanini, Sabatino, Scuri, Colantuoni and Guida.)

The renin angiotensin system and the cholinergic anti-inflammatory pathway have been recently shown to modulate lung inflammation in patients with COVID-19. We will show how studies performed on this disease are starting to provide evidence that these two anti-inflammatory systems may functionally interact with each other, a mechanism that could have a more general physiological relevance than only COVID-19 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Di Maro, Cataldi, Santillo, Chiurazzi, Damiano, De Conno, Colantuoni and Guida.)

Rare genetic obesity disorders are characterized by mutations of genes strongly involved in the central or peripheral regulation of energy balance. These mutations are effective in causing the early onset of severe obesity and insatiable hunger (hyperphagia), suggesting that the genetic component can contribute to 40-70% of obesity. However, genes' roles in the processes leading to obesity are still unclear. This review is aimed to summarize the current knowledge of the genetic causes of obesity, especially monogenic obesity, describing the role of epigenetic mechanisms in obesity and metabolic diseases. A comprehensive understanding of the underlying genetic and epigenetic mechanisms, with the metabolic processes they control, will permit adequate management and prevention of obesity.

Energy homeostasis regulation is essential for the maintenance of life. Neuronal hypothalamic populations are involved in the regulation of energy balance. In order play this role, they require energy: mitochondria, indeed, have a key role in ensuring a constant energy supply to neurons. Mitochondria are cellular organelles that are involved in dynamic processes; their dysfunction has been associated with many diseases, such as obesity and type 2 diabetes, indicating their importance in cellular metabolism and bioenergetics. Food intake excess can induce mitochondrial dysfunction with consequent production of reactive oxygen species (ROS) and oxidative stress. Several studies have shown the involvement of mitochondrial dynamics in the modulation of releasing agouti-related protein (AgRP) and proopiomelanocortin (POMC) neuronal activity, although the mechanisms are still unclear. However, recent studies have shown that changes in mitochondrial metabolism, such as in inflammation, can contribute also to the activation of the microglial system in several diseases, especially degenerative diseases. This review is aimed to summarize the link between mitochondrial dynamics and hypothalamic neurons in the regulation of glucose and energy homeostasis. Furthermore, we focus on the importance of microglia activation in the pathogenesis of many diseases, such as obesity, and on the relationship with mitochondrial dynamics, although this process is still largely unknown.

Taurisolo ® is a pomace extract from Aglianico Grapes, a wine cultivar native to Campania (Southern Italy). It exhibits a very high polyphenolic content and, consumed as a nutraceutical, is effective in reducing the level of Trimethylamine N-oxide (TMAO), a cardiovascular disease risk factor marker. We here show the effects of Taurisolo ® on rat brain microvascular alterations induced by a diminution in cerebral blood flow (CBFD) for 30 min, due to bilateral common carotid artery occlusion, and subsequent blood flow restoration (CBFR) for 60 min. The rat pial microcirculation was investigated by intravital fluorescence microscopy through a parietal closed window implanted into the skull bone. The rat pial arterioles were classified according to Strahler's ordering scheme, from smaller penetrating arterioles up to the larger ones. Western blotting analysis and mass spectrometry (MS)-based metabolomics were used to investigate the expression of endothelial nitric oxide synthase (eNOS) or the presence of peroxidized cardiolipin and several inflammatory mediators, respectively. Radical Oxygen Species (ROS) formation and neuronal loss were assessed. In rats CBFD and CBFR caused a decrease in arteriolar diameter, increase in fluorescent leakage and in adhesion of leukocytes to venular walls, reduction in the length of perfused capillaries and increment of ROS formation with large infarct size. Taurisolo ® , intravenously or orally administered, induced pial arteriolar dilation (up to >30% of baseline), prevented fluorescent leakage, adhesion of leukocytes, ROS formation, while facilitated capillary perfusion and significantly reduced infarct size. These effects were accompanied by an increase in eNOS expression. Mass-spectrometry metabolomics analysis detected a marked decrease in the amount of peroxidized cardiolipin and pronounced reduction in pro-inflammatory prostaglandins and thromboxane Txb2. Altogether, these results extend the nutraceutical potential of Taurisolo ® and suggest their eligibility for preventing brain damage due to ischemia-reperfusion injury., (Copyright © 2020 Lapi, Stornaiuolo, Sabatino, Sommella, Tenore, Daglia, Scuri, Di Maro, Colantuoni and Novellino.)

Background and Aims: A progressive decrease in muscle mass until full-blown sarcopenia may occur in patients on peritoneal dialysis (PD) and worsen their life quality and expectancy. Here we investigate the prevalence of obesity and obesity-associated muscle wasting in PD patients., Patients and Methods: The study design was observational, cross sectional. Body composition was assessed with BIA and BIVA in 88 PD patients (53.4 ± 13.1 years; 67% male). Patients with obesity and/or with reduced muscle mass were identified using FMI and SM/BW cutoff values, respectively. Inflammatory status was assessed by measuring CRP and fibrinogen blood levels., Results: A total of 44.3% of the patients showed a reduced muscle mass (37.5% moderate and 6.8% severe). The prevalence of obesity was 6.1%, 81.8%, and 100% in patients with normal, moderately, and severely reduced muscle mass, respectively (p < 0.05). Of the total, 15.2% of the patients with normal muscle mass, 18.4% of those with moderately reduced muscle mass, and 66.7% of those with severely reduced muscle mass had diabetes. The prevalence of severe muscle mass loss was higher in those with diabetes than in those without diabetes (22.2% vs. 2.8%, p < 0.05). Patients with obesity-associated muscle wasting showed higher fibrinogen (613.9 ± 155.1 vs. 512.9 ± 159.5 mg/dL, p < 0.05) and CPR (1.4 ± 1.3 vs. 0.6 ± 0.8 mg/dL, p < 0.05) blood concentrations than those with normal body composition., Conclusion: Obesity and diabetes were strongly associated with muscle mass loss in our PD patients. It remains to be established whether prevention of obesity with nutritional interventions can halt the occurrence of muscle mass loss in patients on PD., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength. In older people, malnutrition and physical inactivity are often associated with sarcopenia, and, therefore, dietary interventions and exercise must be considered to prevent, delay, or treat it. Among the pathophysiological mechanisms leading to sarcopenia, a key role is played by an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and a decrease in enzymatic antioxidant protection leading to oxidative stress. Many studies have evaluated, in addition to the effects of exercise, the effects of antioxidant dietary supplements in limiting age-related muscle mass and performance, but the data which have been reported are conflicting. In skeletal muscle, ROS/RNS have a dual function: at low levels they increase muscle force and adaptation to exercise, while at high levels they lead to a decline of muscle performance. Controversial results obtained with antioxidant supplementation in older persons could in part reflect the lack of univocal effects of ROS on muscle mass and function. The purpose of this review is to examine the molecular mechanisms underlying the dual effects of ROS in skeletal muscle function and the analysis of literature data on dietary antioxidant supplementation associated with exercise in normal and sarcopenic subjects.

Previously, in normotensive rats, it has been observed that a repetitive sub-maximal mouth opening (mandibular extension, ME) obtained by placing a home-made U-shaped dilator between the superior and inferior dental arches of the rat caused modulation of pial arteriolar tone. The present study was aimed to characterize pial microcirculation in two different cortical brain regions and to assess the hemodynamic effects of a single or double ME on pial arteriolar rhythmic diameter changes in rats rendered hypertensive by dexamethasone administrations. Cranial windows were prepared on parietal and frontal region. Pial arterioles were classified by Strahler method in five orders by in vivo fluorescence microscopy technique associated with a computerized system that permits off-line measurements of arteriolar diameter changes. Two 10 min ME at 10 min interval were applied; then the animals were monitored for further 240 min. Dexamethasone-treated rats exhibited a marked arterial rarefaction and asymmetry of bifurcation in the pial microvascular networks more evident in the frontal region. Starting from ME1, in both cortical areas, the arterioles dilated, and the vasodilation became significant compared to baseline after ME2 for the entire observation period. The spectral analysis carried out on order 2 arteriolar diameter change tracings, showed that double ME increased the spectral density of the frequency components related to endothelial, neuronal and myogenic activities in both the cortical regions studied. In conclusion, double ME has a generalized effect in the cortical areas by restoring the physiological vasomotion of the pial arterioles that was severely impaired by the experimentally hypertension.

This study was aimed to characterize the geometric arrangement of hamster skeletal muscle arteriolar networks and to assess the in vivo rhythmic diameter changes of arterioles to clarify regulatory mechanisms of the capillary perfusion. The experimental study was carried out in male Syrian hamsters implanted with a plastic chamber in the dorsum skin under pentobarbital anesthesia. The skeletal muscle microvessels were visualized by fluorescence microscopy. The vessel diameters, lengths and the rhythmic diameter changes of arterioles were analyzed with computer-assisted techniques. The arterioles were classified according to a centripetal ordering scheme. In hamster skeletal muscle microvasculature the terminal branchings, differentiated in long and short terminal arteriolar trees (TATs), originated from anastomotic vessels, defined "arcading" arterioles. The long TATs presented different frequencies along the branching vessels; order 4 arterioles had frequencies lower than those observed in the order 3, 2, and 1 vessels. The short TAT order 3 arterioles, directly originating from "arcading" parent vessels, showed a frequency dominating all daughter arterioles. The amplitude of diameter variations in larger vessels was in the range 30-40% of mean diameter, while it was 80-100% in order 3, 2, and 1 vessels. Therefore, the complete constriction of arterioles, caused an intermittent capillary blood perfusion. L-arginine or papaverine infusion caused dilation of arterioles and transient disappearing of vasomotion waves and induced perfusion of all capillaries spreading from short and long TAT arrangements. Therefore, the capillary blood flow was modulated by changes in diameter of terminal arterioles penetrating within the skeletal muscle fibers, facilitating redistribution of blood flow according to the metabolic demands of tissues.

The reactive oxygen species (ROS) are known to play a major role in many pathophysiological conditions, such as ischemia and reperfusion injury. The present study was aimed to evaluate the in vivo cyanidin (anthocyanin) effects on damages induced by rat pial microvascular hypoperfusion-reperfusion injury by cerebral blood flow decrease (CBFD) and subsequent cerebral blood flow recovery (CBFR). In particular, the main purpose was to detect changes in ROS production after cyanidin administration. Rat pial microvasculature was investigated using fluorescence microscopy through a cranial window (closed); Strahler's method was utilized to define the geometric features of pial vessels. ROS production was investigated in vivo by 2'-7'-dichlorofluorescein-diacetate assay and neuronal damage was measured on isolated brain sections by 2,3,5-triphenyltetrazolium chloride staining. After 30 min of CBFD, induced by bilateral common carotid artery occlusion, and 60 min of CBFR, rats showed decrease of arteriolar diameter and capillary perfusion; furthermore, increase in microvascular leakage and leukocyte adhesion was observed. Conversely, cyanidin administration induced dose-related arteriolar dilation, reduction in microvascular permeability as well as leukocyte adhesion when compared to animals subjected to restriction of cerebral blood flow; moreover, capillary perfusion was protected. ROS generation increase and marked neuronal damage were detected in animals subjected to CBFD and CBFR. On the other hand, cyanidin was able to reduce ROS generation and neuronal damage. In conclusion, cyanidin treatment showed dose-related protective effects on rat pial microcirculation during CBFD and subsequent CBFR, inducing arteriolar dilation by nitric oxide release and inhibiting ROS formation, consequently preserving the blood brain barrier integrity.

The present study was aimed to in vivo assess the blood flow oscillatory patterns in rat pial microvessels during 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion by laser speckle imaging (LSI). Pial microcirculation was visualized by fluorescence microscopy. The blood flow oscillations of single microvessels were recorded by LSI; spectral analysis was performed by Wavelet transform. Under baseline conditions, arterioles and venules were characterized by blood flow oscillations in the frequency ranges 0.005-0.0095 Hz, 0.0095-0.021 Hz, 0.021-0.052 Hz, 0.052-0.150 Hz and 0.150-0.500 Hz. Arterioles showed oscillations with the highest spectral density when compared with venules. Moreover, the frequency components in the ranges 0.052-0.150 Hz and 0.150-0.500 were predominant in the arteriolar total power spectrum; while, the frequency component in the range 0.150-0.500 Hz showed the highest spectral density in venules. After 30 min BCCAO, the arteriolar spectral density decreased compared to baseline; moreover, the arteriolar frequency component in the range 0.052-0.150 Hz significantly decreased in percent spectral density, while the frequency component in the range 0.150-0.500 Hz significantly increased in percent spectral density. However, an increase in arteriolar spectral density was detected at 60 min reperfusion compared to BCCAO values; consequently, an increase in percent spectral density of the frequency component in the range 0.052-0.150 Hz was observed, while the percent spectral density of the frequency component in the range 0.150-0.500 Hz significantly decreased. The remaining frequency components did not significantly change during hypoperfusion and reperfusion. The changes in blood flow during hypoperfusion/reperfusion caused tissue damage in the cortex and striatum of all animals. In conclusion, our data demonstrate that the frequency component in the range 0.052-0.150 Hz, related to myogenic activity, was significantly impaired by hypoperfusion and reperfusion, affecting cerebral blood flow distribution and causing tissue damage.

Objective: We evaluated whether a short-term course with synbiotics may lower plasma p-Cresol concentrations in kidney transplant patients (KTRs) who accumulate this uremic toxin both because of increased production by their dysbiotic gut microbiome and because of reduced elimination by the transplanted kidneys., Methods: Thirty-six KTRs (29 males, mean age 49.6 ± 9.1 years) with transplant vintage > 12 months, stable graft function, and no episode of acute rejection or infection in the last 3 months were enrolled in this single-center, parallel-group, double-blinded, randomized (2:1 synbiotic to placebo) study. Synbiotic (Probinul Neutro, CadiGroup, Rome, Italy) or placebo was taken at home for 30 days, as 5 g powder packets dissolved in water three times a day far from meals. The main outcome measure was the decrease in total plasma p-Cresol measured by high-performance liquid chromatography at baseline and after 15 and 30 days of placebo or synbiotic treatment., Results: After 15 and 30 days of treatment, plasma p-Cresol decreased by 40% and 33% from baseline (both p < 0.05), respectively, in the synbiotic group, whereas it remained stable in the placebo group. After 30 days of treatment, no significant change was observed in either group in renal function, glycemia, plasma lipids, or albumin concentration. Treatment was well tolerated and did not induce any change in stool characteristics., Conclusion: The results of this pilot study suggest that treatment with synbiotics may be effective to lower plasma p-Cresol concentrations in KTRs. Prospective larger scale, longer term studies are needed to establish whether cardiovascular prognosis could also be improved with this nutritional intervention.

This study aimed to analyze the frequency components present in spontaneous rhythmic diameter changes in rat pial arterioles. Pial microcirculation was visualized by fluorescence microscopy. Rhythmic luminal variations were evaluated via computer-assisted methods. Spectral analysis was carried out on 30-min recordings under baseline conditions and after administration of acetylcholine (Ach), papaverine (Pap), Nω-nitro-L-arginine (L-NNA) prior to Ach, indomethacin (INDO), INDO prior to Ach, charybdotoxin and apamin, and charybdotoxin and apamin prior to Ach. Under baseline conditions all arteriolar orders showed 3 frequency components in the ranges of 0.0095-0.02, 0.02-0.06, and 0.06-0.2 Hz, another 2 in the ranges of 0.2-2.0 and 2.5-4.5 Hz, and another ultra-low-frequency component in the range of 0.001-0.0095 Hz. Ach caused a significant increase in the spectral density of the frequency components in the range of 0.001-0.2 Hz. Pap was able to slightly increase spectral density in the ranges of 0.001-0.0095 and 0.0095-0.02 Hz. L-NNA mainly attenuated arteriolar responses to Ach. INDO prior to Ach did not affect the endothelial response to Ach. Charybdotoxin and apamin, suggested as endothelium-derived hyperpolarizing factor inhibitors, reduced spectral density in the range of 0.001-0.0095 Hz before and after Ach administration. In conclusion, regulation of the blood flow distribution is due to several mechanisms, one of which is affected by charibdotoxin and apamin, modulating the vascular tone., (© 2017 S. Karger AG, Basel.)

The present study was aimed to assess the changes in skin microvascular blood flow (SBF) in newly diagnosed hyperglycemic obese subjects, administered with hypocaloric diet. Adult patients were recruited and divided in three groups: NW group (n=54), NG (n=54) and HG (n=54) groups were constituted by normal weight, normoglycemic and hyperglycemic obese subjects, respectively. SBF was measured by laser Doppler perfusion monitoring technique and oscillations in blood flow were analyzed by spectral methods under baseline conditions, at 3 and 6 months of dietary treatment. Under resting conditions, SBF was lower in HG group than in NG and NW ones. Moreover, all subjects showed blood flow oscillations with several frequency components. In particular, hyperglycemic obese patients revealed lower spectral density in myogenic-related component than normoglycemic obese and normal weight ones. Moreover, post-occlusive reactive hyperemia (PORH) was impaired in hyperglycemic obese compared to normoglycemic and normal weigh subjects. After hypocaloric diet, in hyperglycemic obese patients there was an improvement in SBF accompanied by recovery in myogenic-related oscillations and arteriolar responses during PORH. In conclusion, hyperglycemia markedly affected peripheral microvascular function; hypocaloric diet ameliorated tissue blood flow.

The present study was aimed to evaluate the malvidin's protective effects on damage induced by 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion (RE) in rat pial microcirculation. Rat pial microcirculation was observed using fluorescence microscopy through a closed cranial window. Western blotting analysis was performed to investigate the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) and matrix metalloproteinase 9 (MMP-9) expression. Moreover, MMP-9 activity was evaluated by zymography. Finally, neuronal damage and radical oxygen species (ROS) formation were assessed. In all animals, pial arterioles were classified in five orders of branching according to Strahler's method. In hypoperfused rats, 30 min BCCAO and 60 min RE caused a decrease in arteriolar diameter, an increase in microvascular leakage and leukocyte adhesion, accompanied by decreased capillary perfusion and red blood cell velocity (VRBC). Moreover, marked neuronal damage and evident ROS generation were detected. Conversely, malvidin administration induced arteriolar dilation in dose-related manner, reducing microvascular leakage as well as leukocyte adhesion. Capillary perfusion and VRBC were protected. Nitric oxide (NO) synthase inhibition significantly attenuated malvidin's effects on arteriolar diameter. Western blotting analysis revealed an increase in eNOS and p-eNOS expression, while zymography indicated a decrease in MMP-9 activity after malvidin's administration. Furthermore, malvidin was able to prevent neuronal damage and to decrease ROS generation. In conclusion, malvidin protects rat pial microcirculation against BCCAO/RE injury, preventing blood-brain impairment and neuronal loss. Malvidin's effects appear to be mediated by eNOS activation and scavenger activity.

Introduction: The present study was aimed to assess the in vivo hamster pial microvessel alterations due to 30 min transient bilateral common carotid artery occlusion (BCCAO) and reperfusion (60 min); moreover, the neuroprotective effects of Vaccinium myrtillus extract, containing 34.7% of anthocyanins, were investigated., Materials and Methods: Two groups of male hamsters were used: the first fed with control diet and the other with Vaccinium myrtillus supplemented diet. Hamster pial microcirculation was visualized by fluorescence microscopy through an open cranial window. Pial arterioles were classified according to Strahler's method., Results: In age-matched control diet-fed hamsters, BCCAO caused a decrease in diameter of all arterioles. At the end of reperfusion, the reduction of diameter in order 3 arterioles was by 8.4 ± 3.1%, 10.8 ± 2.3% and 12.1 ± 1.1% of baseline in the 2, 4 and 6 month control diet-fed hamsters, respectively. Microvascular permeability and leukocyte adhesion were markedly enhanced, while perfused capillary length (PCL) decreased. The response to acetylcholine and papaverine topical application was impaired; 2'-7'-dichlorofluoresceine-diacetate assay demonstrated a significant ROS production. At the end of BCCAO, in age-matched Vaccinium myrtillussupplemented diet-fed hamsters, the arteriolar diameter did not significantly change compared to baseline. After 60 min reperfusion, order 3 arterioles dilated by 9.3 ± 2.4%, 10.6 ± 3.1% and 11.8 ± 2.7% of baseline in the 2, 4 and 6 month Vaccinium myrtillus supplemented diet-fed hamsters, respectively. Microvascular leakage and leukocyte adhesion were significantly reduced in all groups according to the time-dependent treatment, when compared with the age-matched control diet-fed hamsters. Similarly, the reduction in PCL was progressively prevented. Finally, the response to acetylcholine and papaverine topical application was preserved and there was no significant increase in ROS production in all groups., Conclusions: In conclusion, Vaccinium myrtillusextract protected pial microcirculation during hypoperfusion-reperfusion, preventing vasoconstriction, microvascular permeability, leukocyte adhesion, reduction in PCL and preserving the endothelium function.

Objective: The aim of the present study was to investigate the in vivo protective effects of hesperidin or diosmin or apigenin on damage induced by transient BCCAO and reperfusion., Methods: Rat pial microcirculation was observed through a closed cranial window, using fluorescence microscopy. Pial arterioles were classified in five orders according to the Strahler's method., Results: After 30 BCCAO and 60 minutes reperfusion, rats showed decreased arteriolar diameter, microvascular leakage, leukocyte adhesion, and reduction in capillary perfusion. Hesperidin and diosmin abolished the reduction in arteriolar diameter, while higher dose apigenin induced dilation by 21.7 ± 2.0% in order three arterioles RE. Nitric oxide synthase inhibition attenuated significantly hesperidin or diosmin or apigenin's effects on arteriolar diameter. Moreover, all these substances reduced microvascular leakage as well as leukocyte adhesion in dose-related manner, while capillary perfusion was protected. Furthermore, reduction in infarcted area and decrease in ROS production were observed., Conclusions: Hesperidin, diosmin, and apigenin showed dose-related protective effects on hypoperfusion-reperfusion injury, causing nitric oxide release and attenuating tissue edema and leukocyte adhesion., (© 2015 John Wiley & Sons Ltd.)

Objective: The present study was aimed to assess the in vivo acute effects of oleuropein or/and pinoresinol, polyphenols widely diffused in natural sources, on rat pial microvascular responses during transient BCCAO and reperfusion., Methods: Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified into five orders of branching. Capillaries were assigned order 0, the smallest arterioles order 1 and the largest ones order 5., Results: Rats subjected to BCCAO and reperfusion showed: arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction in capillary perfusion. Pretreatment with oleuropein or pinoresinol, a higher dose before BCCAO determined dilation in all arteriolar orders RE. Microvascular leakage was reduced as well as leukocyte adhesion and ROS formation, while capillary perfusion was protected. Inhibition of endothelium nitric oxide synthase prior to oleuropein or pinoresinol reduced the effect of these polyphenols on pial arteriolar diameter and leakage. These substances, administered together, prevented microvascular damage to a larger extent., Conclusion: Oleuropein and pinoresinol were both able to protect pial microcirculation from I-reperfusion injury, to increase nitric oxide release and to reduce oxidative stress preserving pial blood flow distribution., (© 2014 John Wiley & Sons Ltd.)