scholarly journals NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1344
Author(s):  
Dorothea D Jenkins ◽  
Hunter G Moss ◽  
Truman R Brown ◽  
Milad Yazdani ◽  
Sudhin Thayyil ◽  
...  

N-acetylcysteine (NAC) and vitamin D provide effective neuroprotection in animal models of severe or inflammation-sensitized hypoxic ischemic encephalopathy (HIE). To translate these FDA-approved drugs to HIE neonates, we conducted an early phase, open-label trial of 10 days of NAC (25, 40 mg/kg q12h) + 1,25(OH)2D (calcitriol 0.05 mg/kg q12h, 0.03 mg/kg q24h), (NVD), for pharmacokinetic (PK) estimates during therapeutic hypothermia and normothermia. We paired PK samples with pharmacodynamic (PD) targets of plasma isoprostanoids, CNS glutathione (GSH) and total creatine (tCr) by serial MRS in basal ganglia (BG) before and after NVD infusion at five days. Infants had moderate (n = 14) or severe HIE (n = 16), funisitis (32%), and vitamin D deficiency (75%). NVD resulted in rapid, dose-responsive increases in CNS GSH and tCr that correlated positively with plasma [NAC], inversely with plasma isofurans, and was greater in infants with lower baseline [GSH] and [tCr], suggesting increases in these PD markers were titrated by neural demand. Hypothermia and normothermia altered NAC PK estimates. NVD was well tolerated. Excluding genetic syndromes (2), prolonged ECMO (2), lost-to-follow-up (1) and SIDS death (1), 24 NVD treated HIE infants have no evidence of cerebral palsy, autism or cognitive delay at 24–48 months. These data confirm that low, safe doses of NVD in HIE neonates decreased oxidative stress in plasma and CNS, improved CNS energetics, and are associated with favorable developmental outcomes at two to four years.

2016 ◽  
Vol 116 (8) ◽  
pp. 1402-1408 ◽  
Author(s):  
Joshua J. Todd ◽  
Emeir M. McSorley ◽  
L. Kirsty Pourshahidi ◽  
Sharon M. Madigan ◽  
Eamon Laird ◽  
...  

AbstractVitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays – a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n22) received 3000 IU (75 µg) vitamin D3daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31–49 nmol/l) and clinical deficiency (<30 nmol/l) were evident in 59, 23 and 18 % of the participants, respectively. Overall, baseline total mean 25(OH)D concentration averaged 59·76 (sd29·88) nmol/l, representing clinical sufficiency. ANCOVA revealed no significant difference in the mean and standard deviation change from baseline in total 25(OH)D concentrations between oral spray and capsule supplementation methods (26·15 (sd17·85)v. 30·38 (sd17·91) nmol/l, respectively;F=1·044, adjustedr20·493,P=0·313). Oral spray vitamin D3is an equally effective alternative to capsule supplementation in healthy adults.


Author(s):  
M. Kolesnyk ◽  
L. Korol ◽  
N. Stepanova ◽  
V. Driianska ◽  
L. Migal ◽  
...  

The purpose of our work was to investigate the effect of immunomodulatory medicines on the intensity of oxidative stress (OS), the cytokines level and the activity of renospecific enzymes in patients with recurrent pyelonephritis (rPN). Methods. A prospective, randomized, open-label study involved of 100 women aged 33.4 ± 8.8 year old. According to the sensitivity of the detected pathogens all patients received antibacterial therapy for two weeks. Along with the main course of antibiotic therapy, 25 patients were assigned Sodium nucleinate at a dose of 0.25 g 4 times per day during 14 days, 18 patients were prescribed Galavit intramuscularly 2 ml per dayfor 10 days, and 27patients were prescribed Proteflazid according to the manufacturer’s instructions. The comparison group consisted of 30 women with rPN who received antibiotic therapy exclusively.Women were screened before and after the treatment. The content of malondialdehyde (MDA), ceruloplasmin (CP), transferrin (TF) and sulfhydryl groups (SH-groups) were determined in the blood by colorimetric method. Oxidative stress index (OSI) was calculated. The concentration of interleukins (IL) -1f, -4, -8, -10, -17, tumor necrosis factor a (TNF-a), transforming growth factor f (TGF-f), monocytic chemoactive protein-1 (MCP-1) and interferon y (IFN-y) were analyzed in the blood of the women using an ELISA. To evaluate the functional state of the renal parenchyma the activity of tubular lysosome enzymes a total f-N-acetylhexosaminidase and f-galactosidase were determined in urine. Results. The use of Sodium nucleinate decreased of the OS activity by reducing MDA level (p <0.001) and increasing the concentration of CP (p < 0.03). The serum levels ofIL-4 (p = 0.007), lL-17 (p = 0.04), TGF-f (p = 0.02) and MCP-1 (p = 0.03) were decrease. The use of Galavit contributed to a statistically significant decrease in the concentration of TNF-a (p <0.001), IL-8(p <0.001), IFN-y (p = 0.001) and TGF-f (p <0.001). The administration of Proteflazid resulted in a decrease in the concentrations of IL-8 and IFN-y, with a decrease in OSI (p =0.04) compared to pre-treatment. All applied immunomodulators partially reduced the activity of renospecific enzymes markers of kidney damage. Conclusions. The use of immunomodulators in the complex therapy of patients with rPN contributes to the partial normalization of functional activity of immune system by the decreasing ofthe production ofcytokines as its mediators and the reducing ofthe OS intensity.


2018 ◽  
Vol 58 (8) ◽  
pp. 1438 ◽  
Author(s):  
David G. Masters

Rapid progress in research on mineral functions in biological systems over the past 20 years has provided new and unexplored implications for health and production in grazing livestock. The strong interaction among calcium (Ca), magnesium (Mg), phosphorus (P), sodium (Na), potassium (K) and vitamin D influences the absorption, utilisation and status of these nutrients, particularly Ca and Mg. An imbalanced intake of Ca, Mg, P, Na, K and vitamin D is common in ruminants grazing pastures and vegetative crops. The interaction may modify susceptibility to clinical hypocalcaemia, hypomagnesaemia and pregnancy toxaemia, or to subclinical and chronic deficiencies of Ca, Mg and Na. However, hypocalcaemia is also associated with endocrine failure. Whether this failure is susceptible to nutritional modulation or even whether supplements of Ca, Mg, Na and vitamin D reduce or exacerbate the risk of metabolic disease in sheep is unclear. Selenium, manganese, zinc, copper, sulfur, vitamin E and vitamin A play synergistic roles in the antioxidant defence mechanism and modulate the consequences of oxidative stress. In extensive grazing systems combined low intakes of these antioxidants are not unusual, particularly in seasonally dry environments and at a time coinciding with the increased oxidative stress that naturally occurs through the reproductive cycle. This oxidative stress is accentuated by heat stress and parasite infection. Oxidative stress in the short-term influences growth, reproduction, offspring survival and health. Long-term, oxidative damage to embryo DNA and changes in RNA expression, may influence lifetime performance of offspring. The high cost of providing mineral supplements to grazing sheep is a deterrence to addressing the implications of multiple mineral deficiencies. New herbaceous and shrub options to increase the botanical and nutritional diversity within pasture and crop-grazing systems may allow livestock to select a heterogeneous diet providing a more balanced mineral intake.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Débora P. Diniz ◽  
Daniela Aparecida Lorencini ◽  
Andresa Aparecida Berretta ◽  
Monica A. C. T. Cintra ◽  
Erica N. Lia ◽  
...  

Background. Propolis is rich in polyphenols, especially flavonoids and phenolic acids, and has significant antioxidant activity, shown mainly in “in vitro” studies. Objective. The aim of this study was to evaluate the antioxidant efficacy and safety of a standardized propolis extract in healthy volunteers. Design. A two-phase sequential, open-label, nonrandomized, before and after clinical trial. Methods. Healthy participants received two EPP-AF® doses (375 and 750 mg/d, P.O, tid) during 7 ± 2 days, starting with the lower doses. Immediately before starting EPP-AF® administration and at the end of each 7-day dosing schedule, blood and urine samples were collected for quantification of 8-OHDG (8-hydroxydeoxyguanosine) and 8-ISO (8-isoprostanes) in urine and GSH (reduced glutathione), GSSG (oxidized glutathione), SOD (superoxide dismutase), FRAP (Ferric Reducing Antioxidant Power), vitamin E, and MDA (malondialdehyde) in plasma. Results. In our study, we had 34 healthy participants (67.7% women, 30 ± 8 years old, 97% white). The 8-ISO, a biomarker of lipid peroxidation, decreased with both doses of EPP-AF® compared to baseline (8-ISO, 1.1 (0.9–1.3) versus 0.85 (0.75–0.95) and 0.89 (0.74–1.0), ng/mg creatinine, P < 0.05 , for 375 and 750 mg/d EPP-AF® doses versus baseline, mean and CI 95%, respectively). 8-OHDG, a biomarker of DNA oxidation, was also reduced compared to baseline with 750 mg/d doses (8-OHDG, 15.7 (13.2–18.1) versus 11.6 (10.2–13.0), baseline versus 750 mg/d, respectively, ng/mg creatinine, P < 0.05 ). Reduction of biomarkers of oxidative stress damage was accompanied by increased plasma SOD activity (68.8 (66.1–73.3) versus 78.2 (72.2–80.5) and 77.7 (74.1–82.6), %inhibition, P < 0.0001 , 375 and 750 mg/d versus baseline, median and interquartile range 25–75%, respectively) and by increased GSH for 375 mg/d EPP-AF® doses (1.23 (1.06–1.34) versus 1.33 (1.06–1.47), μmol/L, P < 0.05 ). Conclusion. EPP-AF® reduced biomarkers of oxidative stress cell damage in healthy humans, with increased antioxidant enzymatic capacity, especially of SOD. This trial is registered with the Brazilian Registry of Clinical Trials (ReBEC, RBR-9zmfs9).


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Rui Dong ◽  
Song Sun ◽  
Xiao-Zhou Liu ◽  
Zhen Shen ◽  
Gong Chen ◽  
...  

Objective. To analyze the levels of fat-soluble vitamins (FSVs) in pediatric patients with biliary atresia (BA) before and after the Kasai procedure. Methods. Pediatric patients with obstructive jaundice were enrolled in this study. The FSV levels and liver function before, 2 weeks after, and 1, 3, and 6 months after the Kasai procedure were measured. Results. FSV deficiency was more obvious in patients with BA than in patients with other cholestatic liver diseases, especially vitamin D deficiency. 25-Hydroxy vitamin D (25-(OH)D) deficiency was more pronounced in younger patients before surgery. The 25-(OH)D level was significantly higher in patients with than without resolution of jaundice 3 months after surgery. At 6 months after surgery, the 25-(OH)D level was abnormally high at 8.76 ng/ml in patients with unresolved jaundice. Conclusions. Preoperative FSV deficiency, particularly vitamin D deficiency, is common in patients with BA. 25-(OH)D deficiency is more pronounced in younger children before surgery. Postoperative FSV deficiency was still prevalent as shown by the lower 25-(OH)D levels in patients with BA and unresolved jaundice. This required long-term vitamin AD supplementation for pediatric patients with BA and unresolved jaundice after surgery.


2006 ◽  
Vol 12 (5) ◽  
pp. 639-645 ◽  
Author(s):  
D T Wade ◽  
P M Makela ◽  
H House ◽  
C Bateman ◽  
P Robson

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21- 814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five ‘serious adverse events’ between them - two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of - tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.


Biomedicine ◽  
2021 ◽  
Vol 41 (4) ◽  
pp. 821-824
Author(s):  
Srilekha V. ◽  
B. Vijayalakshmi ◽  
I. Yogananda Reddy ◽  
Nayiema Fathima

Introduction and Aim:  Fetal growth is a dynamic process that must be monitored in pregnant women to reduce the long-term consequences of fetal anomalies and post-natal effects on their life. The current study was aimed to find out the effectiveness and association of vitamin D on fetal growth during the prenatal period.   Materials and Methods: It was a randomized control trial undertaken in 100 pregnant women who were allocated randomly into two groups based on calcemic state. After giving 6000 IU of vitamin D intervention the fetal growth was measured at the end of 3 months and the variables were obtained before and after the intervention.   Results: The mean difference of fetal weight between groups was 77g was significantly increased to 277g (p<0.01) after 3 months. The mean difference of femur length before intervention was 0.95mm (p-0.18) significantly increased to 3.03mm (p<0.01). Further, the mean biparietal diameter difference was 0.13mm (p-0.92) was substantially increased to 4.77mm(p<0.01).   Conclusion: The current study suggests that the fetal growth variables were significantly increased in post-intervention phases which can be attributed to vitamin D. It has an immense effect on fetal growth which can be supplemented during different trimesters to enhance fetal development.


2019 ◽  
Vol 3 (12) ◽  
pp. 2184-2193 ◽  
Author(s):  
Chellama Jayakumari ◽  
Abilash Nair ◽  
Jabbar Puthiyaveettil Khadar ◽  
Darvin V Das ◽  
Nandini Prasad ◽  
...  

Abstract Context Noncompliance with thyroxine therapy is the most common cause of poor control of hypothyroidism. An open-label prospective study to compare once-weekly thyroxine (OWT) with standard daily thyroxine (SDT) was undertaken. Design Patients taking thyroxine doses of >3 μg/kg/d, with or without normalization of TSH, were included and administered directly observed OWT or nonobserved SDT according to patient preference based on their weight for 6 weeks. Furthermore, patients on OWT were advised to continue the same at home without supervision. Results Twenty six of 34 patients on OWT and 7 of 18 patients on SDT achieved a TSH <10 μIU/mL (P < 0.05), and 2 patients from the SDT arm were lost to follow-up. During home treatment, 15 of 25 at 12 weeks and 19 of 23 contactable patients at a median follow-up of 25 months maintained TSH below target. Thyroxine absorption test was unable to predict normalization of TSH at 6 weeks of OWT therapy. No adverse events were seen with OWT-treated patients over the 12-week follow-up period. OWT has significantly higher efficacy (OR = 5.1) than SDT for patients with thyroxine-resistant hypothyroidism and is not associated with side effects. Conclusion OWT benefits a majority of patients in the long-term treatment of thyroxine-resistant hypothyroidism, in the real-world setting.


Author(s):  
Tal Grunwald ◽  
Shruti Fadia ◽  
Bruce Bernstein ◽  
Matthew Naliborski ◽  
Shufang Wu ◽  
...  

AbstractBackground:Previous studies suggest that vitamin D may play a role in cardiovascular and metabolic health. Oxidative stress has also been implicated in the development of cardiovascular disease. Evidence suggests that vitamin D deficiency may contribute to the occurrence of oxidative stress. This study aimed to determine whether treatment and correction of vitamin D deficiency in obese children led to changes in their metabolic profile, independent of changes in adiposity. In addition, we aimed to determine whether vitamin D deficiency and oxidative stress are causally related in obese children.Methods:In the retrospective arm, chart review identified 32 obese children who experienced normalization of vitamin D deficiency or insufficiency with vitamin D supplementation. We then correlated laboratory and anthropometric data with vitamin D levels. In the prospective arm of the study, urinary 8-isoprostane and hydrogen peroxide were measured before and after correction of vitamin D deficiency/insufficiency and correlated to vitamin D levels in seven patients.Results:In our predominantly Hispanic population of obese children in an urban setting, we demonstrated a cause-effect relationship between vitamin D deficiency and oxidative stress. In contrast, we found no association between vitamin D status, adiposity, and markers of insulin sensitivity, nor any effect of vitamin D treatment on the same parameters.Conclusions:These discordant findings suggest a differential effect of vitamin D on cardiovascular risk factors such as oxidative stress and insulin resistance. To confirm these findings, further prospective studies with larger sample size and longer follow-up are warranted.


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