Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

High-calcium, vitamin D fortified milk is effective in improving bone turnover markers and vitamin D status in healthy postmenopausal Chinese women.

BACKGROUND/OBJECTIVES: Risk for developing osteoporosis increases in Asia. The purpose of the study was to evaluate the impact of a high-calcium vitamin D fortified milk (HCM) intervention on parathyroid hormone (PTH) levels, vitamin D status and markers of bone turnover in postmenopausal Chinese women. SUBJECTS/METHODS: Sixty three women (>55 years) were assigned to receive two servings of either a calcium/vitamin D fortified milk or a control drink for 12 weeks. PTH, serum 25 (OH)D levels, C-telopeptide of type I collagen (CTX) levels and procollagen type I N-terminal propeptide (PINP) were measured at baseline, 2, 8 and 12 weeks of supplementation. RESULTS: Daily calcium intake at baseline ranged between 260 and 482 mg for the HCM, and 252 and 692 mg for the control group. HCM improved serum 25 (OH)D levels significantly (33.13-39.49 nmol/l), while remaining similar in the control group (29.27-28.21 nmol/l). The difference between the groups were significant at week 2, 8 and 12. The percentage change in PTH levels in the HCM group was significant from week 2 onwards compared to the control drink (P<0.017, P<0.05 and P<0.001 at weeks 2, 8 and 12, respectively). Plasma CTX of the HCM group reduced by 25% between weeks 0 and 2, remaining significantly lower and at similar levels up to week 12. The difference between the HCM and control group for PINP reached significance at weeks 8 (P=0.011) and 12 (P=0.003). CONCLUSIONS: The HCM intervention significantly improved vitamin D status and reduced bone turnover over 12 weeks in postmenopausal Chinese women.

Anti-allergic activity of the Sophorae radix water extract in experimental animals.

The water extract of Sophorae radix was tested for its preventive effects against cardiovascular anaphylaxis elicited in experimental animals. In actively sensitized pithed rats, the extract partially protected the animals from death resulting from antigen challenge. Of the cardiovascular changes observed during the anaphylaxis in the pithed animals, the initial pressor response was significantly attenuated by the extract. The extract also improved anaphylactic cardiac dysfunction in passively sensitized isolated guinea hearts: improvement was noted in the contractility, arrhythmic duration and lactate dehydrogenase elevation. The perfusion pressure change to antigen challenge was not altered by the extract in passively sensitized isolated mesenteric artery preparations. The extract however significantly inhibited homologous passive cutaneous anaphylaxis responses in rats. When examined in isolated guinea pig tracheal muscle, the extract did not influence at reasonable concentrations on the contraction elicited by three major anaphylactic mediators, histamine, leukotriene D4 and serotonin. These results suggest that the water extract of Sophorae radix possesses anti-anaphylactic effect in cardiovascular system, primarily acting on the heart not the peripheral resistance vessels.

Metabolism of selenite in men with widely varying selenium status.

OBJECTIVE: This study was undertaken to investigate the metabolism of selenite in men with life-long intakes of deficient, adequate and excess selenium. METHODS: Stable isotopes of selenium were infused for five hours into Chinese men living in deficient, adequate or excessive selenium areas, and 24-hour urine and blood samples were collected daily for the next seven days. Stable isotopic selenium excretion was determined in urine and in whole plasma and plasma fractions. RESULTS: Even though there was a positive correlation of selenium intake with the urinary excretion of this element, this relationship was not linear over the entire range (deficient, adequate, excessive) of selenium intake. When the urine excretion was normalized internally within each group, a sharp increase in the slope of this relationship was found when long-term intake increased to adequate amounts, but the slope reached a plateau when the daily intake exceeded the adequate group. The plasma selenoprotein P fraction was labeled initially, but the incorporation in the glutathione peroxidase fraction subsequently increased by a small amount. A two-month dietary restriction of selenium of the subjects from the excess area did not result in a reduction of urinary excretion of infused selenite. CONCLUSION: A complex relationship exists between long-term intake of selenium and selenium status, and subjects living in the excess area are more saturated with selenium than anticipated. More than two months of depletion are required to affect urinary excretion of selenium.

Quantitative significance of measuring trimethylselenonium in urine for assessing chronically high intakes of selenium in human subjects.

The purpose of the present study was to investigate the effects of Se restriction on the excretion of Se in men who had consumed high levels of this element during their entire lives. With the use of stable isotopes of Se as selenite, the excretion of methylated Se in urine was investigated in Chinese men (n 10) who had habitual chronic high intakes of this element. The relationship between either urine Se or trimethylselenonium (TMSe) to the estimated long-term Se intake was not linear over the entire range of intake, which was also true for the infusion of labelled selenite. A non-linear relationship was also found between urine TMSe and urine Se both for TMSe arising from catabolism of endogenous body Se and that from infused selenite. The data suggest a close precursor-product relationship of urine Se and its TMSe component based on the nearly identical specific activities for these two selenocompounds. Although dimethylselenide in breath was not measured in the present study, combining urinary TMSe with this breath test may be more useful in the assessment of long-term Se status.

Selenium supplementation affects the retention of stable isotopes of selenium in human subjects consuming diets low in selenium.

Twenty-nine women and fifteen men from an area of low Se intake (South Island of New Zealand) consumed 100 micrograms stable 74Se, as selenate given in water after an overnight fast, and blood was collected for 3 weeks. They were then divided into five groups and supplemented with 0, 10, 20, 30 and 40 micrograms Se/d (as selenomethionine) for 5 months. After 5 months, they received a second dose of 74Se identical to the first. Supplementation significantly altered retention of 74Se in the plasma, but not in the erythrocytes or platelets. Subjects receiving the placebo retained the greatest amount, and subjects receiving 30 micrograms supplemental Se/d retained the least 74Se. Supplementation resulted in relatively more isotope being retained in a medium molecular mass protein considered to be albumin, and relatively less in another fraction considered to be selenoprotein P. The lack of many observed changes in retention of stable Se, and the shift in retention among the plasma proteins, suggests that supplemental Se was not being used to replete critical pools of Se, probably because of adaptation to low Se intake.

Distribution of selenium between plasma fractions in guinea pigs and humans with various intakes of dietary selenium.

The distribution of selenium between the plasma fractions was investigated in guinea pigs fed various levels (basal, 0.5, 1.0, 2.0, 4.0, 6.0 and 8.0 mg Se/kg) of dietary selenomethionine (Semet) and in humans living in different areas of China with different selenium status. There was a corresponding increase of selenium concentration in liver, kidney, brain, testis, spleen, heart and muscle with each increase of dietary selenium, but there were no increases of glutathione peroxidase (GPX) activity in liver, brain, testis, heart or muscle in pigs fed any of the selenium levels as compared to controls fed a basal commercial diet. On a percentage distribution basis, the selenium in selenoprotein P decreased and that in the albumin fraction increased with increased dietary intakes of selenium as Semet. The ratios of selenium to albumin in either the plasma or the albumin fractions increased with each increase in dietary selenium. The greatest percentage of selenium was in the albumin fraction of Chinese living in the high selenium areas whereas the greatest amount was in the selenoprotein P fraction in subjects living in deficient and adequate areas of China. Increases in the ratios of selenium to albumin in either the plasma or the albumin fraction also occurred with increases of selenium intake of these subjects. The results indicate that the distribution of selenium in plasma fractions reflect the levels of dietary intakes of Semet.

Changes in myocardial thyroid hormone metabolism and alpha-glycerophosphate dehydrogenase activity in rats deficient in iodine and selenium.

Weanling Wistar rats were fed on diets prepared from grain from areas deficient in I and Se where Keshan disease in endemic. Rats were divided into four groups, each of twelve rats, and received a diet supplemented with: I, Se, I + Se or nothing. At 8 weeks after weaning, myocardial alpha-glycerophosphate dehydrogenase (EC 1.1.1.8; alpha-GPD) activity and indices of Se and thyroid hormone status were determined. The group supplemented with iodine had increased plasma thyroxine levels. There was no difference in plasma triiodothyronine concentration between the groups but triiodothyronine levels in heart were reduced in the Se-supplemented group. Se supplementation increased myocardial glutathione peroxidase activity (EC 1.11.1.9) and the type I 5'-deiodinase (EC 3.8.1.4) activity in rat liver, but no type I 5'-deiodinase activity was detected in heart. alpha-GDP activity in heart was increased in group supplemented with Se, I or both. There was a significant relationship (P < 0.05) between myocardial alpha-GDP activity and plasma thyroxine levels but not between alpha-GDP and myocardial glutathione peroxidase activity. The results indicate that iodine may be more important than Se in energy metabolism in the myocardium, which may give a new insight for the study of the aetiology of Keshan disease in areas where foodstuffs are deficient in both Se and I.

[Determination of the selenomethionine content in grain and human blood].

The authors used the method of cyanogen bromide-fulorimetry to determine the trace amounts of bound selenomethionine (SeMet) in corn, rice, wheat, soybean and human blood. The contents of SeMet in corn samples were found to be 9.2-19014.1 ng/g, and 45.5% to 82% of the total Se in corn samples were in the form of SeMet. Like corn, the proportion of Se in the form of SeMet in total Se in rice, wheat and soybean were 54.9%-86.5%, 50.4%-81.4% and 62.9%-71.8% respectively. The results showed that SeMet is the major chemical form of Se in grain samples determined. The contents of SeMet in two human blood samples (Se content 56.4 ng/g and 71.8 ng/g) were determined as 28.3 ng/g and 53.4 ng/g respectively.

[Method of cyanogen bromide-fluorimetry determination of trace amount of selenomethionine in grain and blood].

Selenomethionine (SeMet) reacted with cyanogen bromide (BrCN) quantitatively forms CH3SeCN. After extracted with CHCl3, the Se of CH3SeCN is acid-digested to Se(IV). Then 2,3-diaminonaphthalene is used to determine the fluorescent Se value of 4,5-benzopiaselenol. The determination limit of this method was 3 ng/g SeMet. The accuracy of 10-500 ng Se in SeMet standard was 91.8%-97.6%. RSD was 1.9%-6.3%. Recoveries for grain and blood were 92.3%-96.7%. RSD was 2.7%-5.1%. The RSD for samples was 2.7%-9.0%. Selenocystine, selenocystiene selenite and methionine did not interfere with the determination.