Urinary Hydroxyproline in the Elderly with Low Leucocyte Ascorbic Acid Levels

Fourteen elderly patients aged 58 to 91 with varying leucocyte ascorbic acid levels had urinary hydroxyproline/creatinine ratios measured before, during, and after treatment with ascorbic acid 1 g. daily for six days. The ratio increased during treatment in those patients whose initial ascorbic acid levels were below 15μg./10⁸ white blood cells. It is suggested that collagen metabolism may be impaired in these patients, and that all such patients should receive ascorbic acid supplements.     

Relationship Between Leucocyte and Plasma Ascorbic Acid Concentrations

Leucocyte and plasma ascorbic acid values were measured in healthy students, adult factory employees, and old people not receiving supplementary vitamin C and in healthy old people receiving 500 mg of vitamin C daily. Significant positive correlations between leucocyte and plasma ascorbic acid were found in all the groups. The regression lines differed significantly between one another within the sexes, but the pooled lines for each sex did not differ significantly in the unsupplemented groups. The relationship between plasma and leucocyte ascorbic acid values in the supplemented group differed significantly from that in the pooled unsupplemented groups.There was a limited range of variation in leucocyte ascorbic acid values compared with the range in plasma values in the supplemented group, whereas there was a wider range of variation in the leucocyte values in the unsupplemented groups. Leucocytes can therefore achieve a saturation level of ascorbic acid. Measurement of leucocyte ascorbic acid concentrations alone does not provide a reliable guide for the estimation of tissue status of ascorbic acid in normal individuals. Leucocyte concentrations provide a measure of the availability of ascorbic acid for storage, and plasma levels give an indication of its metabolic turnover rate. When these values are related the regression lines provide information about the storage and metabolism of ascorbic acid in normal individuals.     

Leucocyte Ascorbic Acid Levels and Vitamin C Intake in Older People

Leucocyte ascorbic acid (L.A.A.) levels and vitamin C intake were measured in a random sample of men and women aged 62-94 years. L.A.A. distributions are positively skewed but log normal. L.A.A. mean values show no age difference in men but are significantly lower in older women. The mean value for all women (23·88μg/10⁸ cells) is significantly higher than that for all men (18·11 μg/10⁸ cells). L.A.A. values are significantly higher in both sexes in the six months July to December. Vitamin C intake distributions are positively skewed but not improved by log transformation. No significant age or sex differences were found except that a significantly greater proportion of men over than of those under 70 years have intakes less than 30 mg daily. Mean intake is significantly higher in men but not in women in the six months April to September, though in both sexes a significantly greater proportion have intakes less than 30 mg daily in October to March compared with April to September. Fifty per cent. of men and 58% of women have intakes less than 30 mg daily, 23·6% of men and 28·1% of women have intakes less than 20 mg daily, and 4·7% of men and 3% of women have intakes less than 10 mg daily. These percentages increase during the winter. A moderate correlation is present between vitamin C intake and L.A.A. level. L.A.A. levels increase in parallel with but lag behind seasonal increases in vitamin C intake.     

Treatment of Duodenal Ulcer with Glycyrrhizinic-acid-reduced Liquorice: A MULTICENTRE TRIAL

A double-blind controlled therapeutic trial of glycyrrhizinic-acid-reduced liquorice 760 mg thrice daily for six weeks was carried out on 90 men with relapse of chronic duodenal ulcer. Effects of treatment were judged by the frequency and severity of pain, the amount of alkali consumed, and the doctors'' and patients'' rating of the clinical response. The results do not show any advantage for the active treatment when compared with the placebo.     

Effects of ascorbic acid on lead induced alterations of synaptic transmission and contractile features in murine dorsiflexor muscle

Lead is a common environmental toxin that affects neuromuscular junction and potentially might cause muscle weakness. Antioxidants like ascorbic acid may protect against lead induced myopathy. The present study measured isometric twitch tensions (evoked either directly by muscle stimulation or indirectly by nerve stimulation) to study effects of ascorbic acid on lead induced alterations at murine dorsiflexor skeletal muscle. Resting membrane potentials (RMPs), endplate potentials (EPPs) and miniature endplate potentials (MEPPs) were also recorded. Forty animals were divided into four groups of n = 10 each. (10 control, 10 lead alone, 10 ascorbic acid alone, 10 lead treated plus ascorbic acid). Lead (1 mg/kg) i.p, was administered daily for 2 weeks before the recording day and ascorbic acid (200 mg/kg, i.p) was given daily for 3 weeks prior to the experiment day. Lead treatment reduced twitch tension significantly (from 4.3 +/- 0.5 g to 2.7 +/- 0.2 g) and delayed half time of decay compared to the control. Similarly MEPPs frequencies were reduced following lead treatment. Application of ascorbic acid prevented twitch tension reduction in lead treated mice (3.3 +/- 0.3 g) and reversed lead induced delay in half time of decay. The negative actions of lead treatment on MEPPs frequencies were also modified with ascorbic acid. It appears that ascorbic acid exerts a protective role against lead induced peripheral nerve and muscle dysfunction. This effect of ascorbic acid on lead induced neuromyopathy is probably mediated via a free radical scavenging mechanism or modification of Ca(2+) homeostasis.     

草鱼外周血细胞数量及其在胁迫或感染下的变化

为了提供可反映草鱼(Ctenopharyngodonidellus)健康状况的血细胞指标的基础数据,研究了4种质量规格组的正常草鱼的外周单位体积血细胞数量,以及分别在硫酸铜或敌百虫处理下和多子小瓜虫感染后的变化。结果表明,1000g组草鱼的单位体积红细胞数显著高于其他3种质量规格组;60g组草鱼的单位体积白细胞数显著低于其他3种质量规格组。硫酸铜或敌百虫处理组的单位体积红、白细胞数显著高于对照组;多子小瓜虫感染组的单位体积白细胞数极显著高于对照组。这里提出一个初步参考指标,60～1000g健康草鱼的红细胞值为1.15×10⁶～3.33×10⁶cells/μL,白细胞值为2.20×10⁵～4.40×10⁵cells/μL。     

Age-related changes in myosin-V myenteric neurons, CGRP and VIP immunoreactivity in the ileum of rats supplemented with ascorbic acid

We examined the effects of ascorbic acid supplementation on myosin-V, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) immunoractivities in the myenteric neurons in aging rats. Male rats were divided into groups: young 90-day-old rats (E90), 345-day-old control rats (E345), 428-day-old control rats (E428), 90- to 345-day-old rats treated with ascorbic acid (1 g/L) (EA345), and 90- to 428-day-old rats treated with ascorbic acid (1g/L) (EA428). The quantitative results showed that aging reduced the number of myosin-V-immunoreactive neurons compared with young animals (E90). Ascorbic acid supplementation in the EA345 and EA428 groups increased the average area of myosin-V neurons by 24.6% and 24.1% compared with the E345 and E428 groups, respectively. When all groups were compared, we observed significant differences for the CGRP- and VIP-immunoractive varicosities of nerve fibers from myenteric neurons. Ascorbic acid supplementation had a neurotrophic effect on all neurons studied, suggesting a neuroprotective role.     

Prevalence of Prostate Cancer in High Boron-Exposed Population: A Community-Based Study

We investigated the possible relationship between boron exposure and prostate cancer (PCa) for men living and being employed at boron mines in villages with rich boron minerals. Out of 456 men studied, 159 were from villages with rich boron sources and boron levels in drinking water of >1?mg?L(-1) and these men formed the study group, while 63 from villages with rich boron sources and boron levels in drinking water of <1?mg?L(-1) were enrolled into control group?1. A further 234 subjects from other villages with no boron mines were considered as control group?2. Prostate specific antigen (PSA) levels could be obtained from a total of 423 men. Urinary boron concentration as an indicator of boron exposure in 63 subjects, prostatic volumes by transrectal ultrasonography in 39 subjects, and prostatic biopsies in 36 subjects were obtained for study and control groups. The daily boron exposure was calculated according to urinary boron levels. Although there was no significant difference among the groups in terms of total PSA levels, the number of subjects with tPSA ≥2.5 and tPSA ≥10.0?ng?dL(-1) prostatic volumes in men whose prostates were biopsied (p?相似文献   

Double-blind comparison of tolamolol,propranolol, practolol,and placebo in the treatment of angina pectoris.

Forty-two patients with angina pectoris have completed a randomized, double-blind trial comparing tolamolol 100 mg and 200 mg with propranolol 80 mg, practolol 100 mg, and placebo, all given three times a day. Tolamolol 200 mg thrice daily was found to be equivalent to propranolol 80 mg thrice daily in anti-anginal efficacy. Anginal attack rates and trinitrin consumption were significantly reduced by all active treatments as compared with the placebo but tolamolol and propranolol were the most effective. Tolamolol 200 mg thrice daily was most effective in reducing blood pressure, while propranolol was most effective in reducing the resting heart rate. All treatments except the placebo significantly increased the amount of exercise which could be performed before angina appeared (exercise work), while tolamolol 200 mg thrice daily significantly reduced Robinson''s index when compared with all other active agents. The degree of S-T segment depression induced by exercise was significantly lessened by both tolamolol and propranolol but not by practolol or placebo. There was no difference in patient preference between tolamolol and propranolol but tolamolol at both dose levels was preferred to practolol. Both tolamolol and propranolol are potent adrenergic beta-receptor antagonists and equal in anti-anginal efficacy but tolamolol has the advantage of being cardioselective. It is superior to practolol.     

Differential effects of protein malnutrition and ascorbic acid deficiency on histidine metabolism in the brains of infant nonhuman primates

Abstract: Male infant nonhuman primates (M. nemes-trina) born in captivity were used in the study. They were divided into three groups. The first group of three animals was fed a 20% casein diet and the second group of six monkeys received a 2.0% casein diet. The third group of four monkeys received a 20% casein diet totally devoid of ascorbic acid for 3.5 weeks before the diet was supplemented with ascorbic acid (20 mg/kg diet). All the diets were given to the animals in two daily rations of 100 g/animal. The monkeys fed a 2% casein diet failed to grow, and after about 3.5 months showed variable degrees of edema, hypoalbuminemia, evidence of psychomotor disturbance, depressed plasma levels of many essential amino acids, and other features consistent with the diagnosis of protein-energy malnutrition. Examination of the brains revealed significant alterations in the levels of histidine (+ 172%) and homocarnosine (+ 146%) in comparison with the control well-fed monkeys. Associated with the increase in brain histidine was a marked elevation of brain histamine level. Protein deficiency also led to poor brain retention of ascorbic acid but not to the same degree observed in the ascorbic acid-deficient animals. The latter group of animals, after receiving their diet for about 8 months, demonstrated a modest elevation in the plasma levels of most amino acids in comparison with controls. Ascorbic acid deficiency elicited a significant reduction (p < 0.01) in brain level of histidine, with hardly any change in homocarnosine level. In addition, vitamin C deficiency produced elevation of brain histamine level comparable to findings in the protein-energy-deficient monkeys. The results suggested that protein deficiency raised brain histamine level mainly through increased availability of the precursor amino acid histidine, while defective degradation might account for the increased brain level of this amine in ascorbic acid-deficient monkeys. Histamine has been proposed to have a predominantly depressant action on relevant neurons, and has also been shown to participate with other neuro-transmitters in influencing the function of the pituitary gland by regulating release of the hypothalamic hormones into the portal vessels. The relevance of the findings of marked increases in brain histamine in experimental protein and ascorbic acid deficiencies to the behavioral and extensive endocrinological alterations seen in human malnutrition deserves some intensive investigation.     

Lack of effect of experimental ascorbic acid deficiency on bile acid metabolism, sterol balance, and biliary lipid composition in man

Extensive studies in animal models indicate that subclinical ascorbic acid deficiency impairs the conversion of cholesterol to bile acid, elevates plasma cholesterol levels, and predisposes to development of cholesterol cholelithiasis. The present study was designed to see if this is also true in man. Five normal volunteers were hospitalized in a metabolic ward and placed on a controlled diet containing 3-4 mg of ascorbic acid each day. Ascorbic acid supplementation was given as follows: control period I (days 1-33), 75 mg/day; deficient period (days 34-96), 0 mg/day; and repletion period (days 97-101), 1000 mg/day. In addition, three of the subjects were studied during a second control period (days 102-139) during which they were given 75 mg/day of ascorbic acid. Ascorbate levels at the end of both control periods were 0.87-1.34 mg/dl in plasma and 19.4-29.5 micrograms/10(8) cells in leukocytes. At the end of the deficient period these levels were 0.09-0.15 mg/dl in plasma and 6.2-10.0 micrograms/10(8) cells in leukocytes, levels approaching those seen in scurvy. There was no effect of ascorbic acid deficiency on plasma cholesterol and triglycerides; plasma cholesterol in high, very low, and low density lipoprotein fractions; biliary lipid composition and saturation index of gallbladder bile; synthesis, fractional turnover, or pool size of either cholic or chenodeoxycholic acids; output of fecal acid or neutral sterols; and fecal sterol balance. Total bile acid pool size calculated by the one-sample technique was reduced 11% in the deficient period compared to control period I (P less than 0.005), and increased to 98.7% of the baseline levels in control period II. However, total bile acid pool calculated by the Lindstedt method did not change during deficiency. These data demonstrate that short-term subclinical ascorbic acid deficiency near the scorbutic range has no significant effect on bile acid and cholesterol metabolism in man.     

Oxidative damage to proteins and decrease of antioxidant capacity in patients with varicocele

To examine oxidative damage to blood proteins in the spermatic vein and seminal plasma antioxidant capacity of patients with varicocele, 30 young male patients with varicocele (group 1), 25 young male patients with subclinical varicocele (group 2), and 15 normal young males without varicocele (group 3) were recruited in this study. Varicocele and subclinical varicocele were confirmed by physical examination and Doppler ultrasonography. Blood samples were drawn from peripheral and spermatic veins before varicocelectomy. Plasma protein carbonyls were measured by a spectrophotometric assay after reacting with 2,4-dinitrophenylhydrazine. Protein thiols and ascorbic acid of seminal plasma were measured by spectrophotometric methods. We found that plasma protein carbonyls in the spermatic veins were significantly higher than those of corresponding peripheral veins in all 30 patients in group 1 and 12 patients in group 2 receiving varicocelectomy. Protein carbonyls in the spermatic veins of patients with varicocele (3.72 +/- 0.56 nmole/mg protein) and patients with subclinical varicocele (3.50 +/- 0.30 nmole/mg protein) were found to be higher than those of the control (2.35 +/- 0.33 nmole/mg protein). Protein thiols were 0.97 +/- 0.96, 1.50 +/- 0.89, and 3.49 +/- 0.81 nmole/ml, and ascorbic acid levels were 1.87 +/- 0.42, 2.13 +/- 0.24, and 2.38 +/- 0.07 mg/dl, in seminal plasma of the patients in groups 1, 2, and 3, respectively. Seminal plasma protein thiols and ascorbic acid levels in group 1 were significantly lower than those in groups 2 and 3, respectively. These results indicate that oxidative stress in the patients with varicocele and subclinical varicocele was higher than that of the control. We suggest that plasma protein carbonyls, and protein thiols and ascorbic acid of seminal plasma are useful markers for the assessment of oxidative stress in patients with varicocele and subclinical varicocele.     

Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension

Hypertension is associated with low plasma ascorbic acid levels and impaired endothelial function. Recent evidence suggests that increased vascular oxidative stress contributes to the pathophysiology of endothelial dysfunction and hypertension. We recently showed that chronic oral ascorbic acid therapy lowers blood pressure in hypertensive patients. We hypothesized that it would also improve endothelial vasomotor function. In a randomized, double-blind, placebo-controlled study, we examined the effect of acute (2 g po) and chronic (500 mg/day for 1 mo) ascorbic acid treatment on brachial artery flow-mediated dilation in 39 patients with hypertension. Compared with 82 age- and gender-matched normotensive controls, these patients had impaired endothelium-dependent, flow-mediated dilation of the brachial artery [8.9 +/- 6.1 vs. 11.2 +/- 5.7% (SD), P < 0.04]. After therapy, plasma ascorbic acid concentrations increased acutely from 50 +/- 12 to 149 +/- 51 micromol/l and were maintained at 99 +/- 33 micromol/l with chronic treatment (both P < 0.001). As previously reported, chronic ascorbic acid therapy reduced systolic and mean blood pressure in these patients. However, acute or chronic ascorbic acid treatment had no effect on brachial artery endothelium-dependent, flow-mediated dilation or on endothelium-independent, nitroglycerin-mediated dilation. These results demonstrate that conduit vessel endothelial dysfunction secondary to hypertension is not reversed by acute or chronic treatment with oral ascorbic acid. The effects of this treatment on resistance vessel vasomotor function warrant further investigation.     

Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents

The present study aimed to investigate the protective role of ascorbic acid (vitamin C) and zinc (Zn) against cadmium (Cd) induced histopathological changes in tissues of liver, kidney, lung and testis of rats as well as chromosomal aberrations. For this purpose, 60 male albino rats were divided into six groups; each group contained 10 animals. The first group served as control and was given only distilled water. The second and third groups received distilled water supplemented with 2 g ascorbic acid/l and 500 mg Zn/l, respectively. The fourth group received a daily oral dose containing 3 mg Cd/kg b.w. (1/30 LD₅₀). The fifth group received Cd + ascorbic acid (3 mg Cd/kg b.w. + 2 g ascorbic acid/l), while the sixth group received Cd + Zn (3 mg Cd/kg b.w. +500 mg Zn/l). The treatment in all groups lasted for 90 consecutive days. Rats exposed to cadmium showed severe histopathological changes in the liver, kidney, lung and testicular tissues as well as chromosomal aberrations such as: break, ring, centromeric separation and polyploidy. Co-treatment with zinc partially improved the histopathological changes and chromosomal aberrations while co-treatment with vitamin C exhibited a more protective role and markedly reduced tissues damage induced by Cd.     

Controlled trial of biofeedback-aided behavioural methods in reducing mild hypertension.

Employees of a large industry were screened for the presence of coronary risk factors. A total of 204 employees, aged 35-64 years, with two or more such factors (serum cholesterol concentration greater than or equal to 6.3 mmol/l (243.6 mg/100 ml), blood pressure greater than or equal to 140/90 mm Hg, and current cigarette consumption greater than or equal to 10 cigarettes a day) were randomly allocated to a biofeedback group receiving training in relaxation and management of stress or a control group. Both groups received simple health education literature. After eight weeks of training, and again eight months later, the biofeedback group showed a significantly greater fall in systolic and diastolic blood pressures than the control group (p less than 0.001). Plasma renin activity and plasma aldosterone concentration were measured in a subsample at entry to the study and again at eight weeks and eight months; both showed a greater reduction in the biofeedback compared with the control group at eight weeks'' follow-up. The greater reduction in blood pressure in the subjects in the biofeedback group compared with the control group (11.0 mm Hg systolic and 8.8 mm Hg diastolic), persisting eight months after the training, suggests that relaxation-based behavioural methods might be offered as a first-time treatment to patients with mild hypertension.     

Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans.

Many constituents present in the human diet may inhibit endogenous formation of N-nitroso compounds (NOC). Studies with human volunteers showed inhibiting effects of intake of ascorbic acid and green tea consumption on nitrosation using the N-nitrosoproline test. The aim of the present study was to evaluate the effects of ascorbic acid and green tea on urinary excretion of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) in humans. Twenty-five healthy female volunteers consumed a fish meal rich in amines as nitrosatable precursors in combination with intake of nitrate-containing drinking water at the Acceptable Daily Intake level during 7 consecutive days. During 1 week before and after nitrate intake a diet low in nitrate was consumed. Using the same protocol, the effect of two different doses of ascorbic acid (250 mg and 1 g/day) and two different doses of green tea (2 g and 4 g/day) on formation of NDMA and NPIP was studied. Mean nitrate excretion in urine significantly increased from control (76+/-24) to 167+/-25 mg/24 h. Intake of nitrate and fish resulted in a significant increase in mean urinary excretion of NDMA compared with the control weeks: 871+/-430 and 640+/-277 ng/24 h during days 1-3 and 4-7, respectively, compared with 385+/-196 ng/24 h (p<0.0002). Excretion of NPIP in urine was not related to nitrate intake and composition of the diet. Intake of 250 mg and 1 g of ascorbic acid per day resulted in a significant decrease in urinary NDMA excretion during days 4-7 (p=0.0001), but not during days 1-3. Also, consumption of four cups of green tea per day (2 g) significantly decreased excretion of NDMA during days 4-7 (p=0.0035), but not during days 1-3. Surprisingly, consumption of eight cups of green tea per day (4 g) significantly increased NDMA excretion during days 4-7 (p=0.0001), again not during days 1-3. This increase is probably a result of catalytic effects of tea polyphenols on nitrosation, or of another, yet unknown, mechanism. These results suggest that intake of ascorbic acid and moderate consumption of green tea can reduce endogenous NDMA formation.     

Cutaneous insulin allergy responsive to oral desensitisation and aspirin.

A diabetic man with no previous history of allergy began to suffer itchy, painful swelling at the sites of injection after three months'' treatment with bovine insulin. Insulin specific IgE concentrations (1.2-2.0 U/ml) were higher than in non-allergic diabetics (mean 0.4 (SD 0.06) U/ml) but lower than in most other patients allergic to insulin (1.0-19.0 U/ml). Standard approaches failed to overcome the allergic reaction, and four separate attempts at desensitisation were unsuccessful. The patient was then given oral insulin 800 U thrice daily together with enteric coated aspirin 1300 mg thrice daily for one week, and subsequent desensitisation with neutral insulin injection was carried out successfully. On stopping the aspirin the original reactions returned, and aspirin was therefore reinstituted as a permanent part of treatment. Whatever the mechanism in this patient, oral desensitisation and aspirin provided a simple method for treating a difficult condition.     

Dehydroepiandrosterone therapy in men with angiographically verified coronary heart disease: the effects on plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen plasma concentrations

INTRODUCTION: The aim of this study was to analyze the influence of DHEA therapy on fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations in men with decreased serum DHEA-S levels and angiographically verified coronary heart disease (CHD). MATERIAL AND METHODS: The study included thirty men aged 41-60 years (mean age 52 +/- 0.90 yr) with serum DHEA-S concentration < 2000 mg/l, who were randomized into a double-blind, placebo-controlled, cross-over trial. Subjects completed the 80 days study of 40 days of 150 mg oral DHEA daily or placebo, and next groups were changed after 30 days of wash-out. Fasting early morning blood samples were obtained at baseline and after each treatment to determine serum hormones levels (testosterone, DHEA-S, LH, FSH and estradiol) and also fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations. RESULTS: Administration of DHEA was associated with 4.5-fold increase in DHEA-S levels. Estrogen levels significantly increased after DHEA from 22.1 +/- 0.7 pg/ml to 26.4 +/- 1.6 pg/l (mean +/- SEM; p < 0.05), while testosterone levels did not changed. Fibrinogen concentrations significantly decreased in DHEA group from 4.5 +/- 0.3 g/l to 3.83 +/- 0.2 g/l (p < 0.05 vs. placebo). Changes of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were not statistical significant (respectively: 8.37 +/- 0.4 ng/ml vs. 8.93 +/- 0.5 ng/ml and 82.3 +/- 6.3 ng/ml vs. 92.7 +/- 9.1 ng/ml (mean +/- SEM; NS vs. placebo). Tolerance of the treatment was good and no adverse effects were observed. CONCLUSIONS: DHEA therapy in dose of 150 mg daily during 40 days in men with DHEAS levels < 2000 mg/l and angiographically verified coronary heart disease (CHD) was connected with significant decreasing of fibrinogen concentration and increasing of estradiol levels, and did not influence on plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations.