Antifungal chemosensitization through induction of oxidative stress: A model for control of candidiasis based on the Lippia origanoides essential oil.

In this work, evaluated the antifungal chemosensitizing effect of the Lippia origanoides essential oil (EO) through the induction of oxidative stress. The EO was obtained by hydrodistillation and analyzed by GC-MS. To evaluate the antifungal chemosensitizing effect through induction of oxidative stress, cultures of the model yeast Saccharomyces cerevisiae ∆ycf1 were exposed to sub-inhibitory concentrations of the EO, and the expression of genes known, due be overexpressed in response to oxidative and mutagenic stress was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) method. Carvacrol and thymol were identified as the main components. The EO was effective in preventing or reducing the growth of the microorganisms tested. The gene expression profiles showed that EO promoted changes in the patterns of expression of genes involved in oxidative and mutagenic stress resistance. The combined use of the L. origanoides EO with fluconazole has been tested on Candida yeasts and the strategy resulted in a synergistic enhancement of the antifungal action of the azolic chemical product. Indeed, in association with EO, the fluconazole MICs dropped. Thus, the combinatorial use of L. origanoides EO as a chemosensitizer agent should contribute to enhancing the efficiency of conventional antifungal drugs, reducing their negative side effects.

Demethylation of Methylmercury in Bird, Fish, and Earthworm.

Toxicity of methylmercury (MeHg) to wildlife and humans results from its binding to cysteine residues of proteins, forming MeHg-cysteinate (MeHgCys) complexes that hinder biological functions. MeHgCys complexes can be detoxified in vivo, yet how this occurs is unknown. We report that MeHgCys complexes are transformed into selenocysteinate [Hg(Sec)4] complexes in multiple animals from two phyla (a waterbird, freshwater fish, and earthworms) sampled in different geographical areas and contaminated by different Hg sources. In addition, high energy-resolution X-ray absorption spectroscopy (HR-XANES) and chromatography-inductively coupled plasma mass spectrometry of the waterbird liver support the binding of Hg(Sec)4 to selenoprotein P and biomineralization of Hg(Sec)4 to chemically inert nanoparticulate mercury selenide (HgSe). The results provide a foundation for understanding mercury detoxification in higher organisms and suggest that the identified MeHgCys to Hg(Sec)4 demethylation pathway is common in nature.

Increased vascular function and superoxide dismutase activity in physically active vs inactive adults living with HIV.

This study compared macro- and microvascular endothelial function and redox status in active vs inactive HIV-infected patients (HIVP) under antiretroviral therapy. Using a cross-sectional design, macro- and microvascular reactivity, systemic microvascular density, and oxidative stress were compared between 19 HIVP (53.1 ± 6.1 year) enrolled in a multimodal training program (aerobic, strength and flexibility exercises) for at least 12 months (60-minutes sessions performed 3 times/wk with moderate intensity) vs 25 sedentary HIVP (51.2 ± 6.3 year). Forearm blood flow during reactive hyperemia (521.7 ± 241.9 vs 361.4% ± 125.0%; P = 0.04) and systemic microvascular density (120.8 ± 21.1 vs 105.6 ± 25.0 capillaries/mm2 ; P = 0.03) was greater in active than inactive patients. No significant difference between groups was detected for endothelium-dependent and independent skin microvascular vasodilation (P > 0.05). As for redox status, carbonyl groups (P = 0.22), lipid peroxidation (P = 0.86), catalase activity (P = 0.99), and nitric oxide levels (P = 0.72) were similar across groups. However, superoxide dismutase activity was greater in active vs inactive HIVP (0.118 ± 0.013 vs 0.111 ± 0.007 U/mL; P = 0.05). Immune function reflected by total T CD4 and T CD8 counts (cell/mm3 ) did not differ between active and inactive groups (P > 0.82). In conclusion, physically active HIVP exhibited similar immune function, but greater macrovascular reactivity, systemic microvascular density, and superoxide dismutase activity than inactive patients of similar age.

A Research Roadmap: Connected Health as an Enabler of Cancer Patient Support.

The evidence that quality of life is a positive variable for the survival of cancer patients has prompted the interest of the health and pharmaceutical industry in considering that variable as a final clinical outcome. Sustained improvements in cancer care in recent years have resulted in increased numbers of people living with and beyond cancer, with increased attention being placed on improving quality of life for those individuals. Connected Health provides the foundations for the transformation of cancer care into a patient-centric model, focused on providing fully connected, personalized support and therapy for the unique needs of each patient. Connected Health creates an opportunity to overcome barriers to health care support among patients diagnosed with chronic conditions. This paper provides an overview of important areas for the foundations of the creation of a new Connected Health paradigm in cancer care. Here we discuss the capabilities of mobile and wearable technologies; we also discuss pervasive and persuasive strategies and device systems to provide multidisciplinary and inclusive approaches for cancer patients for mental well-being, physical activity promotion, and rehabilitation. Several examples already show that there is enthusiasm in strengthening the possibilities offered by Connected Health in persuasive and pervasive technology in cancer care. Developments harnessing the Internet of Things, personalization, patient-centered design, and artificial intelligence help to monitor and assess the health status of cancer patients. Furthermore, this paper analyses the data infrastructure ecosystem for Connected Health and its semantic interoperability with the Connected Health economy ecosystem and its associated barriers. Interoperability is essential when developing Connected Health solutions that integrate with health systems and electronic health records. Given the exponential business growth of the Connected Health economy, there is an urgent need to develop mHealth (mobile health) exponentially, making it both an attractive and challenging market. In conclusion, there is a need for user-centered and multidisciplinary standards of practice to the design, development, evaluation, and implementation of Connected Health interventions in cancer care to ensure their acceptability, practicality, feasibility, effectiveness, affordability, safety, and equity.

Stable and episodic/bolus patterns of methylmercury exposure on mercury accumulation and histopathologic alterations in the nervous system.

The main purpose of the present study was to compare the blood and brain mercury (Hg) accumulation and neurological alterations in adult male and pregnant female/fetal rats following stable and episodic/bolus patterns of methylmercury (MeHg) exposure. In addition, MeHg accumulation in the human body was estimated by a one-compartment model using three different patterns of MeHg exposure. In the adult male rat experiment, doses of 0.3 and 1.5mg MeHg/kg/day were orally administered to the stable groups for 5 weeks, while 7-fold higher doses of 2.1 and 10.5mg MeHg/kg/once a week were administered to the bolus groups. The blood Hg levels increased constantly in the stable groups, but increased with repeated waves in the bolus groups. At completion of the experiment, there were no significant differences in the brain Hg concentrations or neurological alterations between the stable and bolus groups, when the total doses of MeHg were the same. In the pregnant female rat experiment, a dose of 1mg MeHg/kg/day was administered orally to the stable group for 20 days (until 1day before expected parturition), while a 5-fold higher dose of 5mg MeHg/kg/once every 5 days was administered to the bolus group. In the brains of the maternal/fetal rats, there were no significant differences in the Hg concentrations and neurological alterations between the stable and bolus groups. The mean Hg concentrations in the fetal brains were approximately 2-fold higher than those in the maternal brains for both stable and bolus groups. Using the one-compartment model, the Hg accumulation curves in humans at doses of 7µg MeHg/day, 48µg MeHg/once a week, and 96µg MeHg/once every 2 weeks were estimated to be similar, while the bolus groups showed dose-dependent amplitudes of repeated waves. These results suggest that stable and episodic/bolus patterns of MeHg exposure do not cause differences in Hg accumulation in the blood and brain, or in neurological alterations, when the total doses are the same.

Real-time in vivo monitoring of magnetic nanoparticles in the bloodstream by AC biosusceptometry.

BACKGROUND: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. RESULTS: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. CONCLUSIONS: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.

Real-time liver uptake and biodistribution of magnetic nanoparticles determined by AC biosusceptometry.

We describe the development of a joint in vivo/ex vivo protocol to monitor magnetic nanoparticles in animal models. Alternating current biosusceptometry (ACB) enables the assessment of magnetic nanoparticle accumulation, followed by quantitative analysis of concentrations in organs of interest. We present a study of real-time liver accumulation, followed by the assessment of sequential biodistribution using the same technique. For quantification, we validated our results by comparing all of the data with electron spin resonance (ESR). The ACB had viable temporal resolution and accuracy to differentiate temporal parameters of liver accumulation, caused by vasculature extravasation and macrophages action. The biodistribution experiment showed different uptake profiles for different doses and injection protocols. Comparisons with the ESR system indicated a correlation index of 0.993. We present the ACB system as an accessible and versatile tool to monitor magnetic nanoparticles, allowing in vivo and real-time evaluations of distribution and quantitative assessments of particle concentrations.

Oxidative and biochemical responses in Brycon amazonicus anesthetized and sedated with Myrcia sylvatica (G. Mey.) DC. and Curcuma longa L. essential oils.

OBJECTIVE: To investigate the effects of rapid anesthesia and long-term sedation with the essential oils (EOs) of Myrcia sylvatica (EOMS) and Curcuma longa (EOCL) on biochemical and oxidative parameters in matrinxã. STUDY DESIGN: Prospective, randomized, laboratory experiment. ANIMALS: A total of 72 matrinxã (Brycon amazonicus) adults weighing 404.8 ± 27.9 g were divided into eight groups of nine fish. METHODS: Biochemical and oxidative effects were investigated in plasma and tissues of matrinxã subjected to rapid anesthesia (5 minutes) or long-term sedation (360 minutes, simulating the practice of transport) with EOMS (200 µL L-1 and 10 µL L-1, respectively) and EOCL (500 µL L-1 and 40 µL L-1, respectively). RESULTS: Transport simulation without sedation or anesthesia increased lipid peroxidation levels in the gills and kidney of fish in the control group. Anesthesia and sedation with EOs decreased cortisol concentrations and increased lactate concentrations compared with controls. Lipid peroxidation was lower in the brain, gills, liver and kidney of sedated and anesthetized fish, than in the control group. Anesthesia with EOs increased the activity of superoxide dismutase and glutathione-S-transferase in the brain, and catalase in the liver and gills, compared with controls. Long-term sedation with EOs increased superoxide dismutase, glutathione peroxidase and glutathione reductase activities in the brain, catalase in the liver, glutathione peroxidase and glutathione reductase in the gills and superoxide dismutase in the kidney. In general, nonprotein thiols content and total reactive antioxidant potential of tissues were higher after anesthesia and sedation with EOs compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE: The concentrations of EOMS and EOCL used were effective at preventing a stress response and excess of reactive oxygen species formation. For these reasons, these substances may be recommended for use in the transportation of fish to improve survival and animal welfare.

Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMS) in diabetic mice after prolonged high-fat diet.

Intercellular junctions play a role in regulating islet cytoarchitecture, insulin biosynthesis and secretion. In this study, we investigated the animal metabolic state as well as islet histology and cellular distribution/expression of CAMs and F-actin in the endocrine pancreas of C57BL/6/JUnib mice fed a high-fat diet (HFd) for a prolonged time period (8 months). Mice fed a HFd became obese and type 2 diabetic, displaying significant peripheral insulin resistance, hyperglycemia and moderate hyperinsulinemia. Isolated islets of HFd-fed mice displayed a significant impairment of glucose-induced insulin secretion associated with a diminished frequency of intracellular calcium oscillations compared with control islets. No marked change in islet morphology and cytoarchitecture was observed; however, HFd-fed mice showed higher beta cell relative area in comparison with controls. As shown by immunohistochemistry, ZO-1, E-, N-cadherins, α- and ß-catenins were expressed at the intercellular contact site of endocrine cells, while VE-cadherin, as well as ZO-1, was found at islet vascular compartment. Redistribution of N-, E-cadherins and α-catenin (from the contact region to the cytoplasm in endocrine cells) associated with increased submembranous F-actin cell level as well as increased VE-cadherin islet immunolabeling was observed in diabetic mice. Increased gene expression of VE-cadherin and ZO-1, but no change for the other proteins, was observed in islets of diabetic mice. Only in the case of VE-cadherin, a significant increase in islet content of this CAM was detected by immunoblotting in diabetic mice. In conclusion, CAMs are expressed by endocrine and endothelial cells of pancreatic islets. The distribution/expression of N-, E- and VE-cadherins as well as α-catenin and F-actin is significantly altered in islet cells of obese and diabetic mice.

Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury.

In this study, we investigated how mercury (Hg) concentrations in umbilical cord tissue are correlated with those in biomarkers for prenatal exposure to methylmercury (MeHg). Total Hg (T-Hg) concentrations were measured in 54 mother-child paired samples of maternal blood, umbilical cord tissue, cord blood, and maternal hair segments (1-cm incremental segments from the scalp) collected at parturition. MeHg concentrations were also measured in the cord tissue. Median T-Hg and MeHg concentrations in cord tissue on a dry-weight basis (d.w.) were 62.2ng/g and 56.7ng/g, respectively. Proportions of MeHg to T-Hg were approximately 95%. Both T-Hg and MeHg in cord tissue (d.w.) showed better correlations with T-Hg in cord blood than did T-Hg in cord tissue on a wet-weight basis (w.w.). Median T-Hg concentrations in maternal blood, cord blood, and maternal hair (0-1cm from the scalp) were 3.79ng/g, 7.26ng/g, and 1.35 µg/g, respectively. Median T-Hg concentration in cord blood was 1.92 times higher than that in maternal blood. T-Hg in cord tissue (d.w.) showed a strong correlation with that in cord blood (r=0.912, p<0.01). Among the hair segments, T-Hg in cord tissue (d.w.) showed the strongest correlation (r=0.854, p<0.01) with that in maternal hair at 0-1cm from the scalp, reflecting growth for approximately 1 month before parturition. Based on the present results, T-Hg and MeHg concentrations in cord tissue may be useful biomarkers for prenatal MeHg exposure of the fetus, especially reflecting the maternal MeHg body burden during late gestation. The conversion factors for T-Hg and MeHg concentrations in cord tissue (d.w.) to T-Hg concentrations in maternal hair (0-1cm from the scalp) were calculated to be 22.37 and 24.09, respectively. This information will be useful for evaluating maternal MeHg exposure levels in retrospective studies using preserved umbilical cord tissue.

Significance of fingernail and toenail mercury concentrations as biomarkers for prenatal methylmercury exposure in relation to segmental hair mercury concentrations.

OBJECTIVE: To investigate the appropriateness of mercury (Hg) concentrations in fingernails and toenails at parturition for detecting prenatal exposure to methylmercury (MeHg). METHODS: Total Hg concentrations were measured in 54 paired samples of fingernails, toenails, maternal blood, and maternal hair (1cm incremental segments from the scalp toward the tip) collected at 4th weeks of (early) pregnancy, and the same specimens and cord blood collected at parturition. RESULTS: Strong correlations were observed between Hg concentrations in fingernails and toenails at early pregnancy (r=0.923, p<0.01) and at parturition (r=0.895, p<0.01). At early pregnancy, Hg concentrations in fingernails and toenails showed the strongest correlations with those in hair 3-4 cm from the scalp (r=0.818 and r=0.747, p<0.01, respectively) among the 1cm incremental hair segments. Mercury concentrations in fingernails and toenails at parturition represented strong correlations with those in cord blood (r=0.803, p<0.01 for fingernails and r=0.792, p<0.01 for toenails, respectively). At parturition, Hg concentrations in fingernails had the highest correlation with those in hair 0-1cm from the scalp (r=0.918, p<0.01), and Hg concentrations in toenails showed the highest correlation with those in hair at 2-3 cm from the scalp (r=0.872, p<0.01). In addition, Hg concentrations in both finger and toe nails at parturition had equally high (p<0.01) correlation coefficients with hair segments at 0-1, 1-2, and 2-3 cm from the scalp. CONCLUSIONS: Mercury in fingernails and toenails at early pregnancy reflected the maternal Hg body burden level approximately 5 months retroactively. At parturition, Hg levels in fingernails and toenails also showed strong correlations with those in cord blood. In addition, Hg levels in fingernails and toenails at parturition reflected more recent MeHg exposure, compared with those at early pregnancy. These results suggest that fingernails and toenails at parturition are useful biomarkers for prenatal MeHg exposure for mothers and fetuses, especially during the third-trimester of gestation.

Influence of post-transplant immunosuppressive therapy on gastrointestinal transit using biomagnetic method: a pilot study.

BACKGROUND: Immunosuppressive therapy after kidney transplant is necessary to prevent allograft rejection and it is the cause of several gastrointestinal (GI) disorders that have been scantily studied. OBJECTIVES: This study was aimed at investigating the influence of triple immunosuppressive therapy on GI transit in renal transplant patients by employing a biomagnetic technique. METHODS: Twenty-one renal transplant patients underwent triple therapy, which included either tacrolimus (TAC) or cyclosporin A (CsA) associated with prednisone and azathioprine. They were all evaluated, and fifteen other healthy individuals formed the control group. After a standardized meal, GI transit of magnetic markers was assessed using Alternating Current Biosusceptometry (ACB). RESULTS: Patients taking TAC had significantly accelerated gastric emptying and colonic arrival (p ≤ 0.001) when compared with those taking CsA and those in the control group. However, no differences were observed in small bowel transit among the groups studied. Overall, the inter-subject coefficients of variation for gastrointestinal transit parameters were higher for the TAC group and similar for the CsA and control groups. CONCLUSION: This study demonstrated that ACB is a suitable methodology when evaluating the influence of different immunosuppressive therapies on gastrointestinal transit after renal transplantation. Pronounced inter-individual variation was found in patients treated with tacrolimus, thus showing the prokinetic effect of this drug on GI motility. Studies of motility patterns in this population could be useful as complementary information toward determining the mechanisms and the relationship between motility and therapeutic doses.

Antibacterial action against food-borne microorganisms and antioxidant activity of carvacrol-rich oil from Lippia origanoides Kunth.

BACKGROUND: Lippia origanoides Kunth from Northeast Brazil is a plant of pleasant odor used by local people as a food seasoning in substitution the oregano where its carvacrol-rich oil has showed significant antimicrobial activity against human pathogens. METHODS: GC and GC-MS analyzed the plant oil composition and its antibacterial activity was evaluated by disk diffusion and microdilution broth methods. The determination of oil antioxidant activity was made by DPPH radical scavenging assay. Oil toxicity was performed on mice. RESULTS: The main constituents of the oil were carvacrol (47.2%), thymol (12.8%), p-cymene (9.7%), and p-methoxythymol (7.4%). The oil was active against the bacteria of Bacillus cereus, B. subtilis, and Salmonella typhimurium, except for Pseudomonas aeruginosa. The antioxidant activity has displayed a high dose-response (r(2) = 0.92), with the inhibition of DPPH radical from 15 to 82%, at concentrations from 5 to 50 µg/mL, and also by the ß-carotene bleaching assay, which showed a high inhibition of 85.2 ± 6.8 %, corresponding to about 80% of the inhibition of Trolox (93.4 ± 0.7%), used as a standard. The lethal dose (LD50) of the oil was determined in 1673.84 mg mL(-1). CONCLUSION: The results confirmed that the oil of L. origanoides could be utilized for the prevention of food bacterial growth, and as an antioxidative agent for retardation of food oxidation process. The oil has low toxicity, allowing its application in the food industry. Graphical Abstract Aerial parts of Lippia origanoides Kunth.

Effects of high intensity interval versus moderate continuous training on markers of ventilatory and cardiac efficiency in coronary heart disease patients.

BACKGROUND: We tested the hypothesis that high intensity interval training (HIIT) would be more effective than moderate intensity continuous training (MIT) to improve newly emerged markers of cardiorespiratory fitness in coronary heart disease (CHD) patients, as the relationship between ventilation and carbon dioxide production (VE/VCO2 slope), oxygen uptake efficiency slope (OUES), and oxygen pulse (O2P). METHODS: Seventy-one patients with optimized treatment were randomly assigned into HIIT (n = 23, age = 56 ± 12 years), MIT (n = 24, age = 62 ± 12 years), or nonexercise control group (CG) (n = 24, age = 64 ± 12 years). MIT performed 30 min of continuous aerobic exercise at 70-75% of maximal heart rate (HRmax), and HIIT performed 30 min sessions split in 2 min alternate bouts at 60%/90% HRmax (3 times/week for 16 weeks). RESULTS: No differences among groups (before versus after) were found for VE/VCO2 slope or OUES (P > 0.05). After training the O2P slope increased in HIIT (22%, P < 0.05) but not in MIT (2%, P > 0.05), while decreased in CG (-20%, P < 0.05) becoming lower versus HIIT (P = 0.03). CONCLUSION: HIIT was more effective than MIT for improving O2P slope in CHD patients, while VE/VCO2 slope and OUES were similarly improved by aerobic training regimens versus controls.

Antimicrobial and seasonal evaluation of the carvacrol-chemotype oil from Lippia origanoides kunth.

This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the rainy season and 1.6% ± 0.3% in the dry season. Some correlations with climatic parameters were observed. The major components were carvacrol (rainy, 43.5% ± 1.9%; dry, 41.4% ± 2.04%), thymol (rainy, 10.7% ± 1.1%; dry, 10.6% ± 0.9%), p-cymene (rainy, 9.8% ± 0.7%; dry, 10.0% ± 1.4%) and p-methoxythymol (rainy, 9.6% ± 0.8%; dry, 10.4% ± 1.4%). It was found that the antibacterial activity of L. origanoides against Staphylococcus aureus and Escherichia coli was little influenced by the changes in oil composition due to seasonal variation. Against S. aureus, the oil Minimum Inhibitory Concentration (MIC) value was 1.25 µL/mL over ten months. Against E. coli, the oil MIC values ranged from 0.15 µL/mL to 0.31 µL/mL in different months of the year. The Minimum Bactericidal Concentration (MBC) value was 2.5 µL/mL against S. aureus and 1.25 µL/mL against E. coli. The results suggest that the antimicrobial activity identified in the oil remain unchanged for the full year, allowing its medicinal use without any risk of loss or absence of the active principles of the plant.

Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice.

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

Aortocaval fistula delays gastric emptying of liquid test meal in awake rats.

Arteriovenous anastomoses disrupt cardiovascular and renal homeostasis, eliciting hemodynamic adjustments, resetting the humoral pattern, and inducing cardiac hypertrophy. Because acute circulatory imbalance alters gut motor behavior, we studied the effects of arteriovenous fistula placement on the gastric emptying (GE) of a liquid meal in awake rats. After laparotomy, we created an aortocaval fistula (ACF) by aorta and cava wall puncture with a 21-, 23-, or 26-gauge needle. The ACF was not created in the control group, which underwent sham operation. After 12, 24, or 48 h, mean arterial pressure, heart rate, and central venous pressure were continuously recorded, and cardiac output was estimated by thermal dilution. The rats were then gavage fed a test meal (i.e., phenol red in glucose solution), and fractional dye retention was determined 10, 20, or 30 min later. The effect of prior bleeding on ACF-induced GE delay, the role of neuroautonomic pathways, and changes in plasma hormone levels (i.e., angiotensin II, arginine vasopressin, atrial natriuretic peptide, corticosterone, and oxytocin) were evaluated. When compared with the sham-operated group, ACF rats exhibited arterial hypotension, higher (P < 0.05) heart rate, central venous pressure, and cardiac output values and increased (P < 0.05) gastric dye retention, a phenomenon prevented by bilateral subdiaphragmatic vagotomy and hexamethonium treatment. Pirenzepine also impaired the occurrence of gastric delay in subjects with ACF. In addition to causing hyperkinetic circulation, ACF placement delayed the GE of liquid in awake rats, an effect that likely involves a parasympathetic pathway.

Butyrate restores the fat/lean mass ratio balance and energy metabolism and reinforces the tight junction-mediated intestinal epithelial barrier in prediabetic mice independently of its anti-inflammatory and epigenetic actions.

Tissue/cellular actions of butyrate on energy metabolism and intestinal barrier in normal metabolic conditions or prediabetes are still unclear. In this work, we investigated the beneficial effect of dietary supplementation with sodium butyrate on energy metabolism, body mass composition, and intestinal epithelial barrier mediated by tight junction (TJ) in chow diet-fed normal and high-fat diet (HF)-fed prediabetic mice, considering the well-known butyrate action as an epigenetic and inflammatory regulator. Butyrate significantly reduced the fat/lean mass ratio, slightly ameliorated dyslipidemia, restored oral glucose tolerance, and increased basal energy expenditure in prediabetic HF-fed mice but had no effect on control animals. Such effects were observed in the absence of significant alterations in the hypothalamic expression of orexigenic and anorexigenic genes and motor activity. Also, butyrate suppressed the whitening effect of HF on brown adipose tissue but did not affect cell bioenergetics in immortalized UCP1-positive adipocytes in vitro. Butyrate reinforced the intestinal epithelial barrier in HF-fed mice and in Caco-2 monolayers, which involved higher trafficking of TJ proteins to the cell-cell contact region of the intestinal epithelia, without affecting TJ gene expression or the acetylation level of histones H3 and H4 in vivo. All metabolic and intestinal effects of butyrate in prediabetic mice occurred in the absence of detectable changes in systemic or local inflammation, or alterations in endotoxemia markers. Butyrate has no effect on chow diet-fed mice but, in the context of HF-induced prediabetes, it prevents metabolic and intestinal dysfunctions independently of its anti-inflammatory and epigenetic actions.

Biomagnetic methods: technologies applied to pharmaceutical research.

Biomagnetic methods have been designed for a wide range of applications. Recently, such methods have been proposed as alternatives to scintigraphy for evaluating of a number of pharmaceutical processes in vitro as well as under the influence of gastrointestinal physiological parameters. In this review, physical characterization as well as the most recent applications of Superconducting Quantum Interference Device (SQUID), Anisotropic Magnetoresistive (AMR) and AC Biosusceptometry (ACB) in the pharmaceutical research will be explored. Moreover, their current status and how these technologies can be employed to improve the knowledge about the impact of gastrointestinal physiology on drug delivery in association with pharmacokinetic outcomes, termed pharmacomagnetography, will be presented.