Effect of chloride dialysate concentration on metabolic acidosis in aintenance hemodialysis patients

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman’s rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients

The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson’s disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.

Cardiopulmonary exercise testing variables as predictors of long-term outcome in thoracic sarcoidosis

Cardiopulmonary exercise testing (CPET) plays an important role in the assessment of functional capacity in patients with interstitial lung disease. The aim of this study was to identify CPET measures that might be helpful in predicting the vital capacity and diffusion capacity outcomes of patients with thoracic sarcoidosis. A longitudinal study was conducted on 42 nonsmoking patients with thoracic sarcoidosis (median age = 46.5 years, 22 females). At the first evaluation, spirometry, the measurement of single-breath carbon monoxide diffusing capacity (D LCOsb) and CPET were performed. Five years later, the patients underwent a second evaluation consisting of spirometry and D LCOsb measurement. After 5 years, forced vital capacity (FVC)% and D LCOsb% had decreased significantly [95.5 (82-105) vs 87.5 (58-103) and 93.5 (79-103) vs 84.5 (44-102), respectively; P < 0.0001 for both]. In CPET, the peak oxygen uptake, maximum respiratory rate, breathing reserve, alveolar-arterial oxygen pressure gradient at peak exercise (P(A-a)O2), and Δ SpO2 values showed a strong correlation with the relative differences for FVC% and D LCOsb% (P < 0.0001 for all). P(A-a)O2 ≥22 mmHg and breathing reserve ≤40% were identified as significant independent variables for the decline in pulmonary function. Patients with thoracic sarcoidosis showed a significant reduction in FVC% and D LCOsb% after 5 years of follow-up. These data show that the outcome measures of CPET are predictors of the decline of pulmonary function.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations ofN-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh;t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.

Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Drying of sicilian lemon residue: influence of process variables on the evaluation of the dietary fiber produced

In this study, the effect of the process variables of the air-drying of Sicilian lemon residues on some technological properties of the fibers produced was studied. The determination and modeling of desorption isotherms were used to establish the equilibrium moisture content at 60, 75, and 90 °C using the static method with 8 saturated salt solutions. The best fit was obtained with BET and GAB models. The drying process was conducted in a vertical tray dryer and delineated according to a central composite experimental design (2²) using the following as factors: air velocity (0.5, 0.75 and 1 m/s) and temperature (60, 75, and 90 °C), and it presented a good fit to the exponential model (R² > 99.9%). The experimental design responses evaluated were the technological properties of the fibers: water-holding, oil-holding, and swelling capacity. Since these properties were present in high levels, the lemon residues could be used to increase content of fibers in foods resulting in the addition of nutritional benefits for the consumers.

Process variables in the osmotic dehydration of sliced peaches

This paper evaluated the influence of temperature and concentration of the sucrose syrup on the pre-osmotic dehydration of peaches. Physical (colour and texture) and chemical variables (soluble solid content; total sugar, reducing and non-reducing sugar contents; and titratable acidity) were investigated, as well as the osmotic dehydration parameters (loss of weight and water; solids incorporation). An experimental central composite design was employed varying the temperature (from 30 to 50 ºC) and concentration (from 45 to 65 ºBrix) and maintaining the syrup to fruit ratio (4:1), process time (4 hours), and format (slices). The degree of acceptance was used in the sensory analysis evaluating the following characteristics: appearance, taste, texture, colour, and overall quality using a hedonic scale. The results were modelled using the Statistica program (v. 6.0) and the Response Surface Methodology. The mathematical models of the following dimensionless variations yielded significant (p < 0.05) and predictive results: soluble solids content, total and non-reducing sugar contents, titratable acidity, colour parameter L*, and water loss. The models of the attributes colour and appearance yielded significant (p < 0.10) but not predictive results. Temperature was the prevalent effect in the models. The process conditions in the range from 50 to 54.1 ºC and from 45 to 65 ºBrix led to greater water losses and better sensory performances.