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This study aimed to evaluate the effect of early time-restricted eating (eTRE) on metabolic markers and body composition in individuals with overweight or obesity. Seventeen subjects completed a randomized, crossover, and controlled clinical trial. Twelve women and five men participated, with a mean age of 25.8 ± 10.0 years and a BMI of 32.0 ± 6.3 kg/m2. The eTRE intervention included 16 h of fasting (3:00 pm to 7:00 am) and 8 h of ad libitum eating (7:00 am to 03:00 pm) (16:8). The trial included four weeks of interventions followed by a four-week washout period. Body weight, waist and hip circumferences, and body composition measurements were taken. Additionally, a venous blood sample was collected for biochemical determinations. In a before-after analysis, eTRE induced a reduction in BW and BMI in women but this was not significant when compared to the control group. eTRE did not modify any other anthropometric measurements, fasting biochemical parameters, glycemic and insulinemic responses, blood pressure, or subjective appetite. In conclusion, eTRE did not induce beneficial effects on the glycemic and lipid metabolisms, body composition, subjective appetite, or blood pressure. These findings may be attributed to the special characteristics of the population and the short intervention period.

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We previously observed beneficial effects of native banana starch (NBS) with a high resistant starch (RS) content on glycemic response in lean and obese participants. Here, we aimed to determine the effects of NBS and high-amylose maize starch (HMS) on glycemic control (GC) and glycemic variability (GV) in patients with type 2 diabetes (T2D) when treatments were matched for digestible starch content. In a randomized, crossover study, continuous glucose monitoring (CGM) was performed in 17 participants (aged 28-65 years, BMI ≥ 25 kg/m2, both genders) consuming HMS, NBS, or digestible maize starch (DMS) for 4 days. HMS and NBS induced an increase in 24 h mean blood glucose during days 2 to 4 (p < 0.05). CONGA, GRADE, and J-index values were higher in HMS compared with DMS only at day 4 (p < 0.05). Yet, NBS intake provoked a reduction in fasting glycemia changes from baseline compared with DMS (p = 0.0074). In conclusion, under the experimental conditions, RS from two sources did not improve GC or GV. Future longer studies are needed to determine whether these findings were affected by a different baseline microbiota or other environmental factors.

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BACKGROUND: The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery. We determined the effects of its use in patients with enterocutaneous fistula after operative treatment. PATIENTS AND METHODS: Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to the surgery. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications. RESULTS: Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients that did not recur. CONCLUSION: Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.

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The aim of this study was to evaluate the effect of polyamines putrescine, spermidine and spermine on human LDL oxidation and to assess the ability of macrophages derived from type 2 diabetic patients to uptake oxLDL. Polyamine effect was compared with α-tocopherol. Four healthy subjects and eight type 2 diabetic patients were included in this study. To characterize type 2 diabetic patients and non-diabetic subjects, laboratory test were carried out. Glucose, glycated haemoglobin (HbA1C), triglycerides, low (LDL) and high density lipoproteins (HDL) and serum lipid peroxidation were measured in blood. The study was performed in three stages. For each stage, ten experimental conditions comparing the effect of polyamines with α-tocopherol (10µM solutions) on LDL oxidation and the uptake of oxLDL by macrophages were analyzed. MDA concentration was found to be significantly higher in type 2 diabetic patients compared to healthy subjects (5.6±0.58 vs. 2.66±0.31µM MDA, respectively, (P<0.05)). Percent of macrophages containing oxLDL was determined by means of red oil staining. The uptake of oxLDL by macrophages derived from diabetic patients was clear. The uptake of oxLDL was inhibited when the oxidation was prevented by polyamines or α-tocopherol. Spermine showed high antioxidant capacity (96.67±1.53% vs. 25.67±2.30%) compared to α-tocopherol (96.67±1.53% vs. 47.00±7.20%) at the concentration tested. In conclusion, polyamines especially spermine, has a potent antioxidant effect compared to α-tocopherol on human LDL oxidation, followed by spermidine and putrescine. The results have clinical relevance in the diabetic complications and add knowledge on the role of polyamines as natural antioxidants. This research is not a clinical evaluation rather a functional analysis utilizing clinical samples.

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An abnormal glycemic profile, including postprandial glycemia and acute glucose spikes, precedes the onset of overt diabetes in obese subjects. Previous studies have shown the beneficial effects of chronic native banana starch (NBS) supplementation. In this study, we examined the effects of acute ingestion of NBS on glycemic profiles by means of continuous glucose monitoring in obese and lean subjects. In a crossover study, obese and lean subjects consumed beverages containing either 38.3 g of NBS or 38.3 g of digestible corn starch (DCS) twice daily during 4 days. On day 5, a 3-h meal tolerance test (MTT) was performed to evaluate glucose and insulin responses. After 1 week of washout period, treatments were inverted. NBS supplementation reduced the 48-h glycemia AUC in lean, obese, and in the combined group of lean and obese subjects in comparison with DCS. Postprandial glucose and insulin responses at MTT were reduced after NBS in comparison with DCS in all groups. However, no changes were observed in glycemic variability (GV) indexes between groups. In conclusion, acute NBS supplementation improved postprandial glucose and insulin responses in obese and lean subjects during 48 h of everyday life and at MTT. Further research to elucidate the mechanism behind these changes is required.

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The receptor for advanced glycation end-product (RAGE) is the signal transduction receptor which senses a variety of signalling molecules including advanced glycation end products (AGEs), HMGB1, S100/calgranulins, ß-amyloid, phosphatidylserine, C3a and advanced oxidation protein products (AOPPs). It is usually abnormally up-regulated and plays crucial roles during the development of many human diseases such as diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE regulates a number of cell processes of pivotal importance like inflammation, apoptosis, proliferation and autophagy. Therapeutic strategies to block RAGE may represent great therapeutic potentials and therefore it has been under extensive investigation during the last decade. Accordingly, there is a growing interest of unraveling the intracellular signalling pathways by which RAGE controls these disease-related processes. Early studies are mainly focused on inflammatory pathways involving the NFκB and the MAPK pathways. Nevertheless, many novel signalling pathways implicated in other cell processes, such as autophagy, have also recently been found to be activated upon RAGE stimulation and contribute to the detrimental effects of RAGE. In this review, we aim to provide a comprehensive summary of previous and recent studies relating to the complex molecular network of RAGE signalling, with a particular emphasis on RAGE transgenic mouse models.

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The macronutrient component of diets is critical for metabolic control and insulin action. The aim of this study was to compare the effects of high fat diets (HFDs) vs. high carbohydrate diets (HCDs) on metabolic control and insulin resistance in Wistar rats. Thirty animals divided into five groups (n = 6) were fed: (1) Control diet (CD); (2) High-saturated fat diet (HSFD); (3) High-unsaturated fat diet (HUFD); (4) High-digestible starch diet, (HDSD); and (5) High-resistant starch diet (HRSD) during eight weeks. HFDs and HCDs reduced weight gain in comparison with CD, however no statistical significance was reached. Calorie intake was similar in both HFDs and CD, but rats receiving HCDs showed higher calorie consumption than other groups, (p < 0.01). HRSD showed the lowest levels of serum and hepatic lipids. The HUFD induced the lowest fasting glycemia levels and HOMA-IR values. The HDSD group exhibited the highest insulin resistance and hepatic cholesterol content. In conclusion, HUFD exhibited the most beneficial effects on glycemic control meanwhile HRSD induced the highest reduction on lipid content and did not modify insulin sensitivity. In both groups, HFDs and HCDs, the diet constituents were more important factors than caloric intake for metabolic disturbance and insulin resistance.

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Changes in the cellular metabolism assessed by the variability of oxygen consumption (VO(2) ) and carbon dioxide production (VCO(2) ) as well as the association of serum glucose and insulin to energy spectral density (ESD) of VO(2) and VCO(2) were evaluated. Ten nonglucose intolerant and 10 glucose intolerant subjects, aged 21-70 years, were included. Glucose and insulin concentrations and VO(2) and VCO(2) records were collected every 10 min during 3 h. ESD of VO(2) and VCO(2) was estimated and associated with glucose and insulin concentrations. Statistical significance in glucose levels, insulin, and ESD of VO(2) and VCO(2) among nonglucose intolerant subjects and glucose and insulin among glucose intolerance subjects at postload glucose (PLG) state compared with basal state was found. Moreover, glucose was significantly higher in glucose intolerance subjects than nonglucose intolerant subjects for basal and PLG states. These results show an increment in ESD of VO(2) and VCO(2) at PLG state among nonglucose intolerant subjects and suggest that their measurement may be a key indicator of the variability of cellular metabolic activity and contribute to confirm disturbances in glucose metabolism.

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Many enterocutaneous fistulas (ECF) require operative treatment. Despite recent advances, rates of recurrence have not changed substantially. This study aims to determine factors associated with recurrence and mortality in patients submitted to surgical repair of ECF. Consecutive patients submitted to surgical repair of ECF during a 5-year period were studied. Several patient, disease, and operative variables were assessed as factors related to recurrence and mortality through univariate and multivariate analysis. There were 35 male and 36 female patients. Median age was 52 years (range, 17-81). ECF recurred in 22 patients (31%), 18 of them (82%) eventually closed with medical and/or surgical treatment. Univariate analyses disclosed noncolonic ECF origin (p = 0.04), high output (p = 0.001), and nonresective surgical options (p = 0.02) as risk factors for recurrence; the latter two remained significant after multivariate analyses. A total of 14 patients died (20%). Univariate analyses revealed risk factors for mortality at diagnosis or referral including malnutrition (p = 0.03), sepsis (p = 0.004), fluid and electrolyte imbalance (p = 0.001), and serum albumin <3 g/dl (p = 0.02). Other significant variables were interval from last abdominal operation to ECF operative treatment ≤20 weeks (p = 0.03), preoperative serum albumin <3 g/dl (p = 0.001), and age ≥55 years (p = 0.03); the latter two remained significant after multivariate analyses. Interestingly, recurrence after surgical treatment was not associated with mortality (p = 0.75). Among several studied variables, recurrence was only independently associated with high output and type of surgical treatment (operations not involving resection of ECF). Interestingly, once ECF recurred its management was as successful as non-recurrent fistulas in our series. Mortality was associated to previously-reported bad prognostic factors at diagnosis or referral.

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The modification of free amino groups on proteins, lipids, and nucleic acids by non-enzymatic glycosylation produce a variety of complex structures named advanced glycation end products (AGEs). Glycation of these molecules participate in the development of diabetic complications and related diseases. Diabetes mellitus is characterized by short-term metabolic changes in lipid and protein metabolism, and long-term irreversible changes in vascular and connective tissue. AGEs are directly implicated in the development of chronic complications in diabetes such as nephropathy, rethinopathy, neuropathy, and other related diseases such as atherosclerosis, heart disease, stroke, and peripheral vascular disease. In this review, we aim to explain how glycation occurs in different molecules and what the pathological consequence of AGE formation in diabetes mellitus and other diseases are.

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Few fiber supplements have been studied for physiological effectiveness. The effects of native banana starch (NBS) and soy milk (control) on body weight and insulin sensitivity in obese type 2 diabetics were compared using a blind within-subject crossover design. Subjects undertook two phases of 4-week supplementation either with NBS or soy milk. Patients on NBS lost more body weight than when they were on control treatment. Plasma insulin and HOMA-I were reduced after NBS consumption, compared with baseline levels, but not significantly when compared to the control treatment. Results support the use of NBS as part of dietary fiber supplementation.

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Carbon nanotubes are difficult to aerosolize in a controlled manner. We present a method for generating aerosols not only of carbon nanotubes, but also of many reference and proprietary materials including quantum dots, diesel particulate matter, urban dust, and their mixtures, using electrospraying. This method can be used as a teaching tool, or as the starting point for advanced research, or to deliver nanomaterials in animal exposure studies. This electrospray system generates 180 microg of nanotubes per m(3) of carrier gas, and thus aerosolizes an occupationally relevant mass concentration of nanotubes. The efficiency achievable for single-walled carbon nanotubes is 9.4%. This system is simple and quick to construct using ordinary lab techniques and affordable materials. Since it is easy to replace soiled parts with clean ones, experiments on different types of nanomaterial can be performed back to back without contamination from previous experiments. In this paper, the design, fabrication, operation and characterization of our versatile electrospray method are presented. Also, the morphological changes that carbon nanotubes undergo as they make the transition from dry powders to aerosol particles are presented.

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Advanced glycation end-products (AGEs) are heterogeneous groups of compounds that result from the non-enzymatic reaction of reducing sugars with free amino groups of biological molecules such as proteins, lipids, and nucleic acids. A large number of studies have been focused on AGEs metabolism, analysis, treatments, and their implications in the pathogenesis of diseases, especially in diabetes mellitus. Here, we review recent advances in the understanding of pathological complications caused by the production of AGEs. We provide an overview of the most important issues published within this area in last years; we also present the number of scientific papers related to AGEs available since 1950 until 2008 in the most important fields including metabolism, physiology, and pharmacology, thus as analytical methods for AGE detection and quantification and studies carried out in human body fluids. Data were collected from ovidSP.

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Even though the beneficial effects of vitamin E have been experimentally observed, some clinical trials failed to verify a consistent benefit. One reason for this situation has been the difficulty to make comparisons among different studies. There are differences due to subjects, chemical forms of vitamin E, stages of the disease and others. The intake of high doses of vitamin E as a supplement has increased in many countries. Novel studies, have informed that vitamin E not only has antioxidant properties but can acts through precise molecular actions interacting with proteins and enzymes and modulating cellular signaling, transcriptional regulation and apoptosis induction. However, some recent clinical and meta analysis studies have found that daily supplementation with vitamin E 400 IU or higher is associated to increased mortality. In conclusion, a complete understanding of vitamin E actions at the cell does not exist yet and the controversy about its clinical effects is still present. This paper offers current knowledge on the characteristics, metabolism, properties, beneficial effect as well as the potential toxicity of vitamin E.

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Aunque en estudios de laboratorio se han observado efectos potencialmente benéficos de la vitamina E, los resultados de la evaluación clínica son inconsistentes. Una situación que ha limitado el conocimiento en esta área, es la dificultad para establecer comparaciones entre los diferentes estudios. Existen diferencias entre sujetos, tipos de formulaciones, etapas de la enfermedad, y otros aspectos. El consumo de megadosis de esta vitamina se ha incrementado en muchos países. En estudios recientes se ha informado que además de su capacidad antioxidante, esta vitamina tiene acciones moleculares precisas que influyen sobre la actividad de varias enzimas modulando la expresión de genes y la inducción de apoptosis. Sin embargo, algunos estudios clínicos y metaanálisis han informado que dosis de 400 UI/día o mayores de α-tocoferol, se asocian con aumento del índice de mortalidad. Resulta claro que hasta la fecha no se tiene un conocimiento completo de los efectos de estas sustancias a nivel celular y que existe controversia en los resultados de ensayos clínicos. En el presente trabajo se revisa el conocimiento actual sobre las características de esta vitamina, sus principales efectos benéficos, su toxicidad potencial y se discuten los resultados de algunos metaanálisis recientes en relación al aumento del riesgo de mortalidad.

Even though the beneficial effects of vitamin E have been experimentally observed, some clinical trials failed to verify a consistent benefit. One reason for this situation has been the difficulty to make comparisons among different studies. There are differences due to subjects, chemical forms of vitamin E, stages of the disease and others. The intake of high doses of vitamin E as a supplement has increased in many countries. Novel studies, have informed that vitamin E not only has antioxidant properties but can acts through precise molecular actions interacting with proteins and enzymes and modulating cellular signaling, transcriptional regulation and apoptosis induction. However, some recent clinical and meta analysis studies have found that daily supplementation with vitamin E 400 IU or higher is associated to increased mortality. In conclusion, a complete understanding of vitamin E actions at the cell does not exist yet and the controversy about its clinical effects is still present. This paper offers current knowledge on the characteristics, metabolism, properties, beneficial effect as well as the potential toxicity of vitamin E.

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Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by beta-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; beta-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R(f) value obtained (0.24-0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing beta-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients.

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Based on immunohistochemical techniques against connexins and the intercellular flux of staining molecules, it has previously been shown that electrotonic communication occurs among endothelial and vascular smooth muscle cells, this due to the presence of myoendothelial gap junctions. The aim of this study was to evaluate the density of myoendothelial contacts in the left coronary and internal mammary arteries as well as in the left saphenous vein by means of electron microscopy, the distance between both cells participating in an myoendothelial contact with a semi-automatic image analysis system and the presence of homocellular and heterocellular gap junctions between endothelial and smooth muscle cells by using the immunohistochemical technique and confocal microscopy in thoracic aorta were also analyzed. The results are that all blood vessels studied present myoendothelial contacts, while density studies show that they are more abundant in the saphenous vein. The myoendothelial contact distance is constant and in no case the cytoplasmic processes reach the plasma membrane of the partner cell toward which they are advanced. Homocellular gap junctions were found between smooth muscle cells and between endothelial cells. Heterocellular gap junctions were absent, evidencing the possibility that signaling molecules between endothelial and smooth muscle cells may be transferred through plasma membranes as was once thought and not necessarily by electrotonic communication.

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Arginase is the enzyme which synthesizes urea and ornithine, a precursor from which putrescine, spermidine and spermine are formed. These natural polyamines have been implicated in cell growth, replication and wound healing. The present study evaluated the possibility that spermine increases arginase activity and reduces liver damage caused by carbon tetrachloride. Intraperitoneally injected spermine at a dose of 1 mg/kg after a single intragastric administration of carbon tetrachloride (1.6 ml/kg) increased arginase activity (6.30-7.79 microg urea/mg protein per min) (P<0.05) as well as total protein content (0.29-0.37 mg/mg dry weight) in hepatic tissue, compared to the group which only received carbon tetrachloride. When liver cell damage was biochemically assessed, the carbon tetrachloride-treated group showed a 20-fold increase in serum glutamic oxaloacetate transaminase, compared to the control group (P<0.05), and this was significantly diminished by the administration of spermine (P<0.05). Serum triglycerides increased four times compared to the control group as a result of the carbon tetrachloride treatment and were diminished by spermine as well. These results indicate that spermine may play a role in the recovery of liver tissue after carbon tetrachloride-induced liver injury, maybe by increasing the synthesis of putrescine, a polyamine which has been found out to participate in the recovery of the hepatic tissue after an insult with carbon tetrachloride.

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The effect of L-arginine and spermidine on hemoglobin glycation and lipid peroxidation in serum of normal and diabetic rats was studied. Five groups of 40 rats were studied during 20 days and compared with a control group (Group I) that consisted of normal rats (N = 6) not treated with L-arginine or spermidine. Group II, diabetic rats (alloxan 120 mg/kg, i.p. at the day 0 and alloxan 60 mg/kg, i.p. at the day 10) were considered as diabetic control. Group III, diabetic rats treated with 10 mM L-arginine (i.p.). Group IV, diabetic rats treated with 10 microM spermidine (i.p.). Group V, normal rats treated with 10 mM L-arginine (i.p.). Group VI, normal rats treated with 10 microM spermidine (i.p.). The rats of each group were divided in subgroups of four each. Rats were anesthetized and blood was taken from aorta to determine glucose, triglycerides (TGs), total cholesterol (TC), low- and high-density lipoproteins (LDL and HDL), glycated hemoglobin (HbA(1C)), and thiobarbituric acid-reactive substances (TBARS). We observed that the alloxan concentrations used in this study reproduced the clinical manifestations of disease including hyperglycemia (from 116 +/- 7 mg/dl to 435 +/- 80 mg/dl) in 96 hours. As a consequence the levels of TGs, TC, LDL, TBARS, and HbA(1C) were increased, whereas HDL diminished. HbA(1C) concentration was significantly correlated with the concentration of TBARS. The L-arginine and spermidine injection tended to normalize the glycemia from 24 hours, similarly, hyperlipidemia, TBARS, and HbA(1C). From these results, we conclude that l-arginine and spermidine exerted an inhibitory effect of hemoglobin glycation and lipid peroxidation in vivo, which may be relevant in preventing diabetic complications.

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In the searching for new substances with the capacity to protect beta-cells from the toxic effects of alloxan, we evaluated the effect of L-arginine and the polyamines putrescine, spermidine and spermine in a murine experimental model of diabetes. Diabetes was induced by the i.p. injection of either 200 mg/kg (24-h experiments) or 120 mg/kg (12 days experiments) body weight. L-Arginine and polyamines were administered 10 min before or 10 min after alloxan administration, once its half-life had elapsed, respectively. In the 24-h study, serum glucose (199.8+/-27.6 mg/dl) and triglyceride (54.6+/-4.9 mg/dl) concentrations showed a protective effect of spermine, as these parameters were not too high (P < or = 0.05), compared to the alloxan-treated group (415.4+/-47.8 and 90.2+/-11.6 mg/dl, respectively), and were closer to glucose (132.3+/-6.0 mg/dl) and similar to triglycerides (63.8+/-7.1 mg/dl) of the control group. A similar pattern was observed on the parameters measured when L-arginine and polyamines were administered daily for 12 days, starting 10 min after a single alloxan administration, which provides evidence that L-arginine and polyamines are effective in impeding the increase in serum glucose, triglyceride and cholesterol concentration showed on day 3 by the alloxan-treated group, as well as a higher acinar cell regenerative capacity as determined by immunohistochemical techniques. Spermine turning out to be more effective than L-arginine, putrescine or spermidine in counteracting the marked hyperglycemia and triglyceridemia showed by the alloxan-treated group and similar in effect when evaluating cholesterolemia. These results show a clear protective role of L-arginine and polyamines over the pancreatic beta-cell, in addition to the induction of neogenesis from both ductal and acinar cells that leads to the recovery of endocrine pancreatic function in rats with experimental diabetes.

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