Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial.

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.

Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients.

BACKGROUND: This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes. METHODS AND RESULTS: Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating. CONCLUSIONS: These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.

Prevalence and risk factors of vascular calcification in pre-dialysis patients with Balkan endemic nephropathy.

Introduction: Vascular calcifications (VC) are common in patients with chronic kidney disease and present one of manifestations of mineral and bone disorders in these patients. Objective: The aim of this pilot study was to examine the prevalence and risk factors of VC in pre-dialysis patients with Balkan endemic nephropathy (BEN) and other kidney diseases. Methods: The study involved 32 pre-dialysis patients, 15 with BEN and 17 with other kidney diseases. All the patients underwent an interview, objective examination, routine laboratory analyses and measurement of serum concentration of intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 [25(OH)D3] and osteopontin. VCs in iliac, femoral, radial, and digital arteries were evaluated and Adragao VC score was calculated. The samples of radial artery were collected during the first creation of an arteriovenous fistula, and expression of osteocalcin, bone morphogenic protein-2 osteopontin, and matrix Gla-protein in arterial wall were examined. Results: Patients with BEN were significantly older (71.1 ± 6.1 vs. 54.7 ± 11.1 years), but they had significantly lower systolic and mean blood pressure (95.7 ± 13.2 mmHg vs. 104.3 ± 7.4 mmHg) and lower serum concentration of phosphorus (1.32 ± 0.36 mmol/l vs. 1.65 ± 0.35 mmol/l) and cholesterol (4.3 ± 1.1 mmol/l vs. 5.2 ± 0.8 mmol/l) than patients with other kidney diseases. Mean VC score was significantly lower in patients with BEN than in those with other kidney diseases (2.8 ± 1.7 vs. 4.6 ± 1.8; p = 0.009), but expression of four examined proteins in arterial wall differed insignificantly between the two groups. VC score correlated significantly with serum concentrations of cholesterol, triglycerides (positively), and iPTH (negatively). Conclusion: Pre-dialysis BEN patients had a significantly lower mean score of VC than patients with other kidney diseases.

Evidence that cranberry juice may improve augmentation index in overweight men.

The stiffening of arteries is a key step in atherogenesis leading to cardiovascular disease. It has been suggested that dietary polyphenols may be cardioprotective through possible favorable effects on oxidative stress and vascular function. The present study was undertaken in order to examine the effect of consuming low-calorie cranberry juice cocktail (CJC), a source of polyphenols, on arterial stiffness in abdominally obese men. We hypothesize that regular CJC consumption will reduce circulating oxidized low-density lipoproteins concentrations and have a beneficial impact on endothelial function. Thirty-five men (mean age ± SD: 45 ± 10 years) were randomly assigned to drink 500 mL CJC/day (27% juice) or 500 mL placebo juice (PJ)/day for 4 weeks in a double-blind crossover design. Augmentation index (AIx), an index of arterial stiffness, was measured by applanation tonometry of the radial artery and the cardiometabolic profile was assessed in each participant before and after each phase of the study. We found no significant difference in AIx changes between men who consumed CJC or PJ for 4 weeks (P = .5820). Furthermore, there was no between-treatment difference in changes in AIx responses to salbutamol (P = .6303) and glyceryl trinitrate (P = .4224). No significant difference was noted in other cardiometabolic variables between men consuming PJ or CJC. However, a significant within group decrease in AIx (mean decrease ± SE; -14.0 ± 5.8%, P = .019) was noted following the consumption of 500 mL CJC/day for 4 weeks. Our results indicate that the effect of chronic consumption of CJC on AIx was not significantly different from changes associated with the consumption of PJ. However, the significant within-group decrease in AIx following CJC consumption in abdominally obese men may deserve further investigation.

Osteopontin expression in vascular smooth muscle cells in patients with end-stage renal disease.

beta-glycerophosphate, a phosphate donor, and uremic sera induce osteopontin (OPN) expression in bovine vascular smooth muscle cells (VSMCs). However, the correlations of serum phosphorus level with OPN expression, and blood urea nitrogen (BUN) level with OPN expression in humans have not previously been reported. The purpose of the current study is to compare the expression of OPN in VSMCs with clinical data in patients with end-stage renal disease (ESRD). The radial arteries of 33 patients (21 male and 12 female patients) were examined to determine the expression of OPN and collagen type I (Col I) by immunohistochemistry. The correlation of the expression of bone matrix proteins with clinical data was analyzed. Between the low-serum phosphorus (<6 mg/dL) group and high-serum phosphorus (> or =6 mg/dL) group, significant differences were detected in the expression of OPN (P = 0.0049) and the levels of BUN (P = 0.0005), serum phosphorus (P < 0.0001) and calcium x phosphorus products (P < 0.0001). Moreover, between the low-BUN (<70 mg/dL, N = 19) group and high-BUN (> or =70 mg/dL) group, significant differences were detected in the expression of OPN (P = 0.0039) and the levels of BUN (P = 0.0002), serum phosphorus (P = 0.0002) and calcium x phosphorus products (P = 0.0003). We have shown that hyperphosphatemia or azotemia is associated with the expression of OPN in VSMCs in patients with ESRD.

Nitric oxide and endothelium-derived hyperpolarizing factor in human arteries and veins.

BACKGROUND: We have investigated and compared nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization in the human internal mammary artery (IMA), radial artery (RA), saphenous vein (SV), and coronary artery. MATERIALS AND METHODS: Vessel segments taken from coronary artery bypass grafting or heart transplantation patients were placed in an organ chamber. NO-sensitive electrode or intracellular glass microelectrode was used to study NO or EDHF in response to acetylcholine (ACh) and bradykinin (BK). RESULTS: The resting membrane potential of the smooth muscle cells of IMA, RA, and SV was -58 +/- 0.84 (n = 61), -61 +/- 1.3 mV (n = 46, p = 0.03), and -62 +/- 0.9 mV (n = 23, p = 0.0001) respectively. BK- (10(-7) M) induced EDHF-mediated hyperpolarization (-10.9 +/- 1.5 mV, n = 7) in the IMA was significantly greater than that in RA (-5.8 +/- 0.9 mV, n = 6, p = 0.04) and SV (-5.1 +/- 0.5 mV, n = 8, p < 0.01). The basal release of NO in IMA (16.8 +/- 1.9 nM) was significantly higher than that in RA (11.1 +/- 1.0 nM, n = 12, p = 0.02) and in SV (9.9 +/- 2.8 nM, n = 13, p < 0.001). The stimulated release of NO to BK in IMA was significantly greater than that in RA (44.3 +/- 4.0 vs 25.8 +/- 3.6 nM, n = 8, p = 0.004). The duration of NO release was longer in IMA than in RA or in SV. CONCLUSIONS: The basal and stimulated release of NO and EDHF-mediated hyperpolarization in the IMA are significantly greater than that in the RA and SV. EDHF exists in all these human vessels. This study reveals the differences among human vessels regarding the endothelial function that have implications in vasospasm, coronary protection, or long-term graft patency.

Accumulation of calcium and phosphorus accompanied by increase of magnesium and decrease of sulfur in human arteries.

To elucidate the accumulation of elements in the arteries with aging, the authors investigated age-related changes of elements in human arteries, such as the thoracic aorta, femoral, basilar, coronary, radial, and common iliac arteries by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 17 men and 9 women, ranging in age from 55 to 92 yr in the cases of the five arteries, except for the common iliac arteries, in which the subjects consisted of 16 men and 8 women, ranging in age from 65 to 93 yr. It was found that there were significantly direct correlations between calcium and phosphorus contents and between calcium and magnesium contents in all of the six arteries: thoracic aorta, femoral, basilar, coronary, radial, and common iliac arteries. Significantly direct correlations were also found between phosphorus and magnesium contents in the five arteries, except for the basilar artery. In contrast, significantly inverse correlations were found between calcium and sulfur contents and between phosphorus and sulfur contents in the four arteries, except for the coronary and radial arteries. These revealed that the accumulation of calcium and phosphorus in the arteries was accompanied by an increase of magnesium in the arteries and by a decrease of sulfur in the arteries.

Selective accumulations of aluminum in five human arteries.

The aim of the present study was to determine variability of aluminum (Al) accumulation in human arteries and to observe the relationship between Al and five other elements (Ca, Fe, Mg, P, and Si) in the arteries. The Al contents in the thoracic aorta, basilar, coronary, femoral, and radial arteries of 26 human subjects were estimated by an inductively coupled plasma-atomic emission spectrometer and compared quantitatively to five elements. Al was detected in 88% of the cases in both the femoral and radial arteries, 73% in the coronary artery, 58% in the aorta, and 31% in the basilar artery. The average Al content was highest in the femoral artery (48.3 +/- 15.0 microg/g dry weight) and lowest in the basilar artery (8.1 +/- 3.6 microg/g). The Al had positive correlations with P, Ca, or Mg in both the aorta and femoral artery, and with Ca or P in the basilar artery. In the coronary artery, a correlation was found between Al and Si. No relationships were found between Al and each of the five elements in the radial artery. From these results, Al varied widely among the five arteries and accumulated more in the femoral and radial arteries but less in the basilar artery. These accumulations of Al were positively correlated with Ca or P in several arteries, but not sufficiently to explain the accumulation of Al. Further investigations are required to understand the mechanism of the variability of Al accumulation in the arteries.

High accumulation of elements in the human femoral artery.

The relative contents (RCs) of elements in the femoral arteries as well as the thoracic aorta, coronary, basilar, and radial arteries from 26 subjects within the age range between 55 and 92 yr old, were analyzed by inductively coupled plasma atomic emission spectrometry. The RCs of calcium and phosphorus in the femoral arteries started to increase before the age of 60 yr. The RCs of magnesium increased after the age of 70 yr. However, the RCs of sulfur did not change significantly within the age range between 55 and 92 yr. With regard to localization of the mineral accumulations in the femoral arterial wall, it was found that the accumulations of calcium and phosphorus occurred only in the tunica media, only in the tunica intima, or in both the tunica media and the tunica intima. The manner of accumulation of calcium and phosphorus in the femoral arterial wall was different from that in the aortic wall. The average RCs of calcium in the 26 specimens were the highest in the femoral artery, followed in descending order by the thoracic aorta, coronary, basilar, and radial arteries. The average RCs of phosphorus were highest in the thoracic aorta, followed by the coronary, femoral, basilar, and radial arteries. It is noted that the accumulation of mineral elements never occurred uniformly in all the arteries.