Saint John's Wort as an antidepressant

Although in Germany St. John's wort (Hypericum perforatum) is the most widely prescribed antidepressant, in the Netherlands little is known about it. Nevertheless patients ask for it more often or take it as self-medication. There has been much research into the antidepressant efficacy of hypericum extracts, but the methodological quality has been moderate. In recent years studies with a much better design were published in European journals. Hypericum extract in a dosage of 900 mg/day is effective in mild to moderately severe depressed outpatients. Maintenance therapy has not been studied sufficiently yet. The side effect profile is on a placebo level. Recently interactions with other medications were described (decrease of plasma level/clinical efficacy of protease inhibitors, warfarin, theophyllin, cyclosporin, third generation oral contraconceptives, digoxin and phenprocoumon). A patient's request to be treated with hypericum extract can be considered, e.g. if the patient experiences troublesome side effects on other drugs. In case hypericum is the initial antidepressant and the effect falls short of the expectations, treatment with a synthetic standard antidepressant should be applied.     

Efficacy and Acceptability of Pharmacological Treatments for Depressive Disorders in Primary Care: Systematic Review and Network Meta-Analysis

PURPOSEThe purpose of this study was to investigate whether antidepressants are more effective than placebo in the primary care setting, and whether there are differences between substance classes regarding efficacy and acceptability.METHODSWe conducted literature searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013. Randomized trials in depressed adults treated by primary care physicians were included in the review. We performed both conventional pairwise meta-analysis and network meta-analysis combining direct and indirect evidence. Main outcome measures were response and study discontinuation due to adverse effects.RESULTSA total of 66 studies with 15,161 patients met the inclusion criteria. In network meta-analysis, tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine), a low-dose serotonin antagonist and reuptake inhibitor (SARI; trazodone) and hypericum extracts were found to be significantly superior to placebo, with estimated odds ratios between 1.69 and 2.03. There were no statistically significant differences between these drug classes. Reversible inhibitors of monoaminoxidase A (rMAO-As) and hypericum extracts were associated with significantly fewer dropouts because of adverse effects compared with TCAs, SSRIs, the SNRI, a noradrenaline reuptake inhibitor (NRI), and noradrenergic and specific serotonergic antidepressant agents (NaSSAs).CONCLUSIONSCompared with other drugs, TCAs and SSRIs have the most solid evidence base for being effective in the primary care setting, but the effect size compared with placebo is relatively small. Further agents (hypericum, rMAO-As, SNRI, NRI, NaSSAs, SARI) showed some positive results, but limitations of the currently available evidence makes a clear recommendation on their place in clinical practice difficult.     

Determinants of plasma levels of beta-carotene and retinol. Skin Cancer Prevention Study Group

The associations of retinol and beta-carotene plasma concentrations with eight personal variables and the use of seven classes of cardiovascular drugs were studied in over 1,750 patients with nonmelanoma skin cancer enrolled at four American study centers in a cancer prevention clinical trial. Dietary carotene and female sex were positively related to beta-carotene levels, while cigarette smoking and Quetelet index were negatively related. Use of vitamins, beta blockers, or other antihypertensive drugs were also related to beta-carotene levels, but were associated with much smaller changes in these levels. Age and use of other types of cardiovascular drugs were not associated with beta-carotene levels to a statistically significant extent. There was no statistically significant interaction of smoking and dietary carotene in predicting plasma beta-carotene levels. The multiple correlation coefficient between log plasma beta-carotene and the full model was R = 0.50. Retinol levels were positively related to male sex and use of vitamins, diuretics, beta blockers, other cardiovascular drugs, and menopausal estrogens, and negatively related to current cigarette smoking and use of nitrates. The multiple correlation coefficient between plasma retinol and the full model was R = 0.33. These findings confirm the importance of several previously reported predictors of plasma retinol and beta-carotene levels. They also identify several new predictors of these micronutrient levels.     

Clinical pharmacology and toxicology of antidepressants

Described as the drugs of choice in treating acute depression, the tricyclics are unusual in that too high a dosage may be as ineffective as one that is too low, and plasma levels may vary as much as 30-fold among patients given the same dosage. After the recommended approach to determining appropriate dosage has been tried, the 15% or so of patients who do not respond are not likely to benefit from a switch of drugs.     

Plasma concentrations of transsulfuration pathway products during nasoenteral and intravenous hyperalimentation of malnourished patients

We have monitored the plasma concentrations of products of the transsulfuration pathway in 11 undernourished noncirrhotic patients, and in 10 cachectic cirrhotic subjects, before and during nasoenteral nutrition with Vivonex (Norwich-Eaton Pharmaceuticals, Norwich, NY) or total parenteral nutrition (TPN) with FreAmine III (American McGaw, Irvine, CA). In the cirrhotic cases eating a mixed diet, levels of taurine, cysteine, plasma glutathione, and free choline were subnormal. During nasoenteral hyperalimentation, methionine was elevated while cysteine, glutathione, and free choline levels remained depressed. During TPN, levels of taurine, cysteine, protein-bound cysteine, glutathione, free choline, and phosphatidyl choline were depressed and methionine was elevated. In the noncirrhotic cases eating a mixed diet, only the free choline concentration was low. During nasoenteral hyperalimentation, the plasma levels of both free choline and total carnitine were depressed. During TPN, plasma levels of cystine, protein-bound cysteine, total carnitine, free choline, and phosphatidyl choline were subnormal. These data suggest that biosynthesis of several products of the transsulfuration pathway may be inadequate in both cirrhotic and noncirrhotic patients during TPN with FreAmine III.     

The relationship between plasma taurine and other amino acid levels in human sepsis

Although reports of decreased plasma taurine in trauma, sepsis and critical illness are available, very little is known about the relationships among changes in plasma taurine, other amino acid levels and metabolic variables. We analyzed a large series of plasma amino acid profiles obtained in trauma patients with sepsis who were undergoing total parenteral nutrition. The correlations between plasma taurine, other amino acid levels, parenteral substrate doses and metabolic and cardiorespiratory variables were assessed by regression analysis. Post-traumatic hypotaurinemia was followed by partial recovery toward less abnormal values when sepsis developed. Levels of taurine were directly and significantly related to levels of glutamate, aspartate, beta-alanine and phosphoethanolamine (and unrelated to other amino acids). Levels of these amino acids increased simultaneously with increasing doses of leucine, isoleucine and valine in total parenteral nutrition. Decreasing taurine was associated with increasing lactate, arteriovenous O(2) concentration difference and respiratory index, and with decreasing cholesterol and cardiac index. These results characterize the relationships between plasma taurine and other amino acid levels in sepsis, provide evidence of amino acid interactions that may support taurine availability and show more severe decreases in plasma taurine with the worsening of metabolic and cardiorespiratory patterns.     

Augmentation of corticosterone release by means of a caffeine-ethanol interaction in rats.

We examined whether the acute treatment with caffeine delivered before an ethanol injection would augment plasma corticosterone (CORT) levels. The effect of caffeine on blood ethanol levels was also assessed. After 10 days of acclimatization to the colony room conditions, male Wistar rats were injected with either caffeine (5 mg/kg, ip) or saline 30 min before the delivery of ethanol (0.8 g/kg, ip) or saline, respectively. Trunk blood was then collected at 15 and 30 min after the ethanol injection for determination of plasma CORT and blood ethanol levels. CORT was measured with the use of radioimmunoassay, and blood ethanol levels were determined with the use of gas chromatography. The results showed that although caffeine and ethanol delivered singly failed to augment plasma CORT levels, the combination of both drugs produced elevations in plasma CORT levels at 15 and 30 min. These findings were found to be unrelated to changes in ethanol metabolism as caffeine failed to alter blood ethanol levels within the period tested. It was argued that the present elevations in plasma CORT levels observed in animals administered caffeine and ethanol may play a role in the caffeine-induced elevations in ethanol drinking observed elsewhere.     

Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%-50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins) do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with beta-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important.     

胶体金免疫层析法同时检测肉类食品中八种兽药残留物

目的研制八联盘检测肉类食品中多种兽药残留物。方法将应用胶体金免疫层析法制备好的8种试纸条组装成多联检测盘,评价该盘检测兽药残留物的灵敏度、准确度、特异性和稳定性。结果通过在空白样本中加标,确定了不同样本(猪肉、牛肉和羊肉)中14种兽药的检测限;60份样本的八联盘检测结果与仪器确证结果一致,检出禁用药和限用药各6份,符合率达100%;检测盘中的试纸条与类似药物之间无交叉反应,特异性好;八联盘在室温条件下可保存至少12个月,稳定性较好。结论该八联盘操作简便、快速、检测结果准确、稳定,为兽药残留现场监控提供了有力工具。     

Lowering of plasma cholesterol levels in free-living adolescent males; use of natural and synthetic polyunsaturated foods to provide balanced fat diets.

Two hundred and twenty-nine adolescent male pupils, attending two boarding schools, participated in a study, under free-living dietary conditions, designed to assess the effects on plasma lipids of altering only the type and not the amount of dietary fat. The students were monitored for 6 weeks on three different diets. During the first study period, dietary changes comprised substituting a polyunsaturated dried "filled" milk and products derived therefrom for conventional dairy products (diet A). The second dietary phase involved replacing all meat and dairy products with equivalent polyunsaturated ruminant fat products (diet B). The third period consisted of a control diet of conventional dairy and meat products. During both polyunsaturated diets a 14% reduction in plasma cholesterol was achieved compared with control levels. Low-density lipoprotein cholesterol was similarly suppressed. A greater decrease in plasma cholesterol of 19-21% was recorded in those pupils with initial cholesterol levels greater than 230 mg/dl. There was no significant difference in plasma triglycerides between diet A and the control diet whereas the triglyceride levels were 16.5% lower during diet B. The fall in plasma cholesterol coincided with an increase in plasma triglyceride linoleate from 8% to 19% of total triglyceride fatty acids. Dietary analysis of the pupils' diet indicated an increase in the ratio of polyunsaturates to saturates from 0.27 during the control period to 1.08 on the dried filled milk and 0.90 on the polyunsaturated ruminant fat products. A palatability survey showed that both the dried filled milk and the polyunsaturated ruminant fat products were as well accepted by the pupils as the conventional products. The results suggest that such products could, if introduced to the general population, play an important part in plasma cholesterol suppression in the hope that this would significantly reduce the incidence of coronary artery disease.     

Cancer and low levels of plasma cholesterol: the relevance of cholesterol precursors and products to incidence of cancer

BACKGROUND: It is proposed that the mechanism responsible for the low plasma cholesterol-cancer associations reported in the literature is related to blood and tissue levels of cholesterol precursors and products, reflecting rates of cholesterol synthesis rather than the plasma cholesterol level itself. METHODS: Data have been collated from Japanese and Northern European studies on plasma levels of a cholesterol precursor, lathosterol, and one product, cholestanol, each a marker of cholesterol metabolism. Situations in which the rate of cholesterol synthesis is altered have also been examined for their relationship to cancer incidence. RESULTS: The data though minimal suggest that lathosterol and cholestanol may be higher in the blood of the Japanese compared with the Northern Europeans, despite lower plasma cholesterol levels in the Japanese. In accord with the hypothesis the Japanese have a low incidence of many cancers. Cholesterol synthesis is lowered when dietary cholesterol and fat intake are increased and incidence of cancer is increased in these states. Conversely cholesterol synthesis is raised in vegetarianism, the Mediterranean diet, pregnancy, and lactation, and incidence of some cancers is lowered. CONCLUSIONS: At least some of the variation in cancer incidence with plasma cholesterol levels and also with dietary saturated fat and cholesterol, as well as vegetarianism, the Mediterranean diet, pregnancy, and lactation, can be accounted for by their effects on the rate of cholesterol synthesis and the level of cholesterol precursors and/or products so generated.     

Effects of ingestion of tomatoes, tomato juice and tomato purée on contents of lycopene isomers, tocopherols and ascorbic acid in human plasma as well as on lycopene isomer pattern

Tomatoes are an important part of the diet. Lycopene, the predominant carotenoid in tomatoes, is hypothesised to mainly mediate the health benefits of tomato products. Anticancer activity of tomato products and lycopene has been suggested by numerous studies. The aim of the present study was to investigate the effect of ingestion of three different tomato-based foodstuffs on plasma contents of lycopene, tocopherols and ascorbic acid. Because isomers of lycopene may have different biological activities, a special interest was to look how the lycopene isomer pattern is changed depending on the matrix of tomato products. Following a 2-week depletion phase volunteers ingested 12.5 mg lycopene/d for 4 weeks comprising tomatoes, tomato juice or tomato purée. The basal levels of lycopene in plasma were comparable for all groups and decreased significantly during the 2 weeks of depletion to approximately half of the basal values. Following intervention, plasma lycopene concentration increased significantly. Conversely, supplementation did not significantly affect levels of tocopherols and ascorbic acid in plasma. Regarding isomers of lycopene, the (Z)-lycopene:(all-E)-lycopene plasma isomer ratio was significantly changed during the study for all groups. A remarkable enrichment of the relative contents of (5Z)-lycopene was observed during the depletion period, which supports the hypothesis that lycopene (Z)-isomers are formed within the human body after ingestion of (all-E)-lycopene. After dietary intervention with lycopene-rich products the isomer ratios returned to those observed at the start of the study. Further investigations will clarify the process of isomerisation in more detail.     

Medicine use and vitamin status in elderly Europeans

The relationship between medicine use and plasma levels of beta-carotene, retinol, alpha-tocopherol, cobalamin, folate and pyridoxal-5'-phosphate was investigated in 676 men and 759 women, aged 74 to 79 years, from 13 towns in 11 European countries. Information on medicine use was obtained by questionnaire. Vitamin concentrations were determined in fasting blood samples. The percentage of subjects using drugs was 83%. Antihypertensive drugs, analgesics, diuretics, sleeping tablets and psychotropics were most frequently used. Plasma retinol concentration, plasma beta-carotene concentration in smokers and plasma alpha-tocopherol concentration in ex-smokers were significantly different between subjects using drugs and those taking no medication. As expected the plasma level of beta-carotene was lower in medicine users (relative adjusted difference: -0.26 micromol/l, 95% CI[-0.45;0.01]). However, plasma levels of retinol and alpha-tocopherol were higher (absolute adjusted difference: 0.07 micromol/l, 95% CI[0.00;0.14] and 2.29 micromol/l, 95% CI[0.56;4.02] respectively). Folate and cobalamin were only significantly different with use of specific drug groups. The results of this study suggest that in rather healthy elderly people medicine use affects plasma levels of beta-carotene and cobalamin in a negative way, and has a positive effect on plasma levels of retinol, alpha-tocopherol and folate.     

Plasma fluorescent oxidation products as potential markers of oxidative stress for epidemiologic studies

Currently lacking are stable and easily measured biomarkers that can reflect oxidative stress in humans. Fluorescent oxidation products may fulfill all three of these criteria. Fasting plasma levels of fluorescent oxidation products were measured in 286 controls in a study of coronary heart disease among US men aged 47-81 years; the study concluded in 2006. Other biomarkers in plasma were also measured, and cardiovascular risk factors such as smoking, hypertension, age, and physical activity were assessed by questionnaire. Indicators of oxidative stress, including smoking, hypertension, and reduced renal function, were associated with greater fluorescent oxidation products in both age- and multivariate-adjusted analyses (for each, p for trend < 0.01). In a multivariate-adjusted analysis, levels of fluorescent oxidation products were 45% higher in current smokers than in never smokers and 61% higher in men who smoked more than 25 cigarettes/day versus 1-4 cigarettes/day. The levels of this marker were 17% higher in hypertensive men than in normotensive men and 20% higher in men in the lowest versus the highest quartile of glomerular filtration rate. Levels were 57% higher in men with both hypertension and reduced renal function than in men with neither. The association of fluorescent oxidation products with several indicators of oxidative stress suggests that this measure could be a useful global marker of oxidative stress for large epidemiologic studies.     

HCG与血浆抑制素A联合预测妊娠期高血压疾病的临床意义

目的:探讨HCG、INH-A与妊高征的发病关系及对妊高征的预测价值。方法:随访125例孕14～20周孕妇的妊娠结局,其中发生妊高征者20例。采用ELISA法测定INH-A与β-HCG。结果:妊高征组血浆INH水平(412.24±50.14)ng/L,明显高于正常妊娠组(308.34±68.25)ng/L(P<0.05),重度妊高征患者INH水平高于轻度患者。妊高征组孕妇β-hCG水平(1563.25±320.48)mIU/ml明显高于正常妊娠组(1245.85±296.56)mIU/ml(P<0.05),妊高征组INH-A水平与HCG水平呈正相关(r=0.714,P<0.05)。结论:INH-A、β-HCG水平均能敏感预测妊高征,且妊高征时INH-A和HCG的量呈同步增长,HCG与INH-A联合应用动态检测两者的变化更有利于早期预测妊高征。     

Exacerbating effect of dietary 12-keto oleic acid on vitamin E deficiency in the rat.

12-Keto oleic acid, possibly one of the oxidation products of long-chain, unsaturated fatty acids, was added to the feed of weanling male rats at the 1% level. Their growth curves, tissue weights, plasma alkaline phosphatase, GOT, and GPT activities, and plasma and liver lipid (cholesterol, triglyceride and phospholipid) levels were investigated and compared with those of weanlings fed a vitamin E deficient diet. Both the diet containing 12-keto oleic acid and the diet deficient in vitamin E decreased the growth rate of body weight and tissue weight, and increased the liver triglyceride and cholesterol levels. Parallel with these, increased hemolysis and stimulation of lipid peroxidation and fluorescent production in the liver homogenate were observed. Elevated plasma alkaline phosphatase and GOT activities which may be considered to be due to a functional disorder of the liver were also observed.     

Lipid peroxidation and antioxidants status in patients with papillary thyroid carcinoma in India

The levels of lipid peroxidation products (TBARS), non-enzymatic antioxidants and enzymatic antioxidants activity were investigated in plasma and erythrocytes of twenty clinically diagnosed stage II papillary thyroid cancer patients and an equal number of age and sex matched healthy subjects. An increase in the levels of lipid peroxidation products, decrease in non-enzymatic antioxidants levels and enzymatic antioxidant activities in plasma and erythrocytes were detected in papillary thyroid cancer patients as compared to healthy subjects. Impairment in antioxidant defence mechanisms are responsible for enhanced lipid peroxidation observed in plasma and erythrocytes of papillary thyroid cancer patients.     

The content of Ca, Mg, Fe and Cu in selected species of herbs and herb infusions

The aim of the study was the recognition of the contents and distributions of calcium, magnesium, iron and copper in 6 herb species (matricaria chamomila, tilia cordata, equisetum arvense, melissa officinalis, mentha piperita, hypericum perforatum) and in the herb infusions. The samples were digested using a microwave oven, and the elements concentration was determined by AAS method. The following levels of Ca, Mg, Mg and Cu in the herbs were determined: 6872-19802 mg/kg Ca, 4630-8530 mg/kg Mg, 149.9-415.6 mg/kg Fe and 15.15-24.64 mg/kg Cu. The values of extractions in the infusions of herb were as follows: 16.1-73.8% Ca, 14.4-37.3% Mg, 5.1-9.7% Fe, 13.1-21.8% Cu. This indicates, that a very small part of the iron can be potentially treated as a bioavailable fraction for persons, using plant drugs as infusions. One glass of infusion (250 cm3) contain elements in quantities corresponding to: 0.78-2.61% average daily dietary intake (ADDIs) of Ca, 0.76-1.36% ADDIs of Mg, 0.26-0.38% ADDIs of Cu and only 0.15-0.33% ADDIs of Fe.     

The effect of acarbose and miglitol (BAY-M-1099) on postprandial glucose levels following ingestion of various sources of starch by nondiabetic and streptozotocin-induced diabetic rats

The effect of two alpha-glucosidase inhibitors, acarbose (BAY-G-5421) and miglitol (BAY-M-1099), on postprandial glucose levels following intubation of corn, rice, spaghetti and potato (0.5 g/100 g body wt) was evaluated in nondiabetic and diabetic rats. The peak plasma glucose level and total incremental glucose were significantly decreased following ingestion of each starch source when acarbose (8 mg/100 g body wt) or BAY-M-1099 (2 mg/100 g body wt) were simultaneously intubated. The effect of both inhibitors was more pronounced in diabetic rats than in nondiabetic rats, and their effect on digestion was in a substrate-specific manner. Potato starch digestion was inhibited 58 +/- 11% by BAY-M-1099, and by acarbose, 38 +/- 9%. Rice starch digestion was inhibited by 65 +/- 2% by acarbose, and by BAY-M-1099, only 30 +/- 9%. Both drugs had a similar inhibitory effect when corn or spaghetti was ingested. BAY-M-1099 appears to be more potent than acarbose on both a weight-per-weight basis and on a molar basis. When corn or rice was used, only 2 mg of BAY-M-1099 was required to achieve a similar inhibitory effect to that of 8 mg of acarbose (9.7 X 10(-3) M) vs. 12.2 X 10(-3) M). Since both drugs blunted to varying degrees the rise in glucose level following starch ingestion, they may be a useful adjuvant in the treatment of diabetic subjects. Simultaneous use of both drugs in therapeutic treatment should be seriously considered.     

Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults

There is strong evidence that whole-grain foods protect against heart disease. Although underlying mechanisms and components are unclear, betaine, found at high levels in wheat aleurone, may play a role. We evaluated the effects of a diet high in wheat aleurone on plasma betaine and related measures. In a parallel, single-blinded intervention study, 79 healthy participants (aged 45-65 y, BMI ≥ 25 kg/m(2)) incorporated either aleurone-rich cereal products (27 g/d aleurone) or control products balanced for fiber and macronutrients into their habitual diets for 4 wk. Fasting blood samples were taken at baseline and postintervention (4 wk) from participants. Compared with the control, the aleurone products provided an additional 279 mg/d betaine and resulted in higher plasma betaine (P < 0.001; intervention effect size: 5.2 μmol/L) and lower plasma total homocysteine (tHcy) (P = 0.010; -0.7 μmol/L). Plasma dimethylglycine and methionine, which are products of betaine-mediated homocysteine remethylation, were also higher (P < 0.001; P = 0.027) relative to control. There were no significant effects on plasma choline or B vitamins (folate, riboflavin, and vitamin B-6). However, LDL cholesterol was lower than in the control group (P = 0.037). We conclude that incorporating aleurone-rich products into the habitual diet for 4 wk significantly increases plasma betaine concentrations and lowers tHcy, which is attributable to enhanced betaine-homocysteine methyltransferase-mediated remethylation of homocysteine. Although this supports a role for betaine in the protective effects of whole grains, concomitant decreases in LDL suggest more than one component or mechanism may be responsible.