Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats

Chinese herbs nephropathy (CHN), a rapidly progressive interstitial fibrosis of the kidney, has been described in approximately 100 young Belgian women who had followed a slimming regimen containing some Chinese herbs. In 4 patients multifocal transitional cell carcinomas (TCC) were observed. Aristolochic acid (AA), suspected as the causal factor of CHN, is a well known carcinogen but its ability to induce fibrosis has never been demonstrated. The objective of this study was to evaluate the latter using doses of AA, durations of intoxication and delays of sacrifice known to yield tumours in rats. We also tested the hypothesis that a possible fibrogenic role of AA was enhanced by the other components of the slimming regimen. Male and female rats were treated orally with 10 mg isolated AA/kg per day for 5 days/week, or with approximately 0.15 mg AA/ kg per day 5 days/week contained in the herbal powder together with the other components prescribed in the slimming pills for 3 months. The animals were killed respectively 3 and 11 months later. At sacrifice, animals in both groups had developed the expected tumours but not fibrosis of the renal interstitium. Whether the fibrotic response observed in man is due to species and/or strain related differences in the response to AA or to other factors, remains to be determined. Interestingly, despite the addition of fenfluramine and diethylpropion, two drugs incriminated in the development of valvular heart disease, no cardiac abnormalities were observed.     

Dietary practices and lipid intake in relation to plasma lipid profile in Hong Kong Chinese

OBJECTIVE: To study dietary lipid intake and plasma lipid profile of the Hong Kong Chinese population as part of a territory wide survey on cardiovascular risk factors. DESIGN: Randomised age and sex stratified survey. SUBJECTS: 1010 subjects aged 25-74 y (500 men, 510 women). MEASUREMENTS: A food frequency method with food tables compiled for Hong Kong was used for nutrient quantitation, while a separate questionnaire was used to examine dietary practices. Plasma lipid profile was estimated using standard laboratory methods. RESULTS: Total calorie, fat, saturated fatty acid (SFA), poly- and mono-unsaturated fatty acid (PUFA and MUFA), and cholesterol intake were higher in men; however when adjusted for caloric intake no difference was observed. Men had lower intake of PUFA as percentage of total energy had a higher Hegsted Score compared with women. Subjects consuming beans twice or more per week had lower total cholesterol and LDL-cholesterol concentrations. Overall, the population dietary intake was close to the ideal for cardiovascular health: percentage fat not greater than 30% of the total calorie intake, saturated fat intake not greater than 10% of calories, and cholesterol less than 180 mg/1000 Kcal. CONCLUSION: The dietary pattern for Hong Kong Chinese appear to be satisfactory with respect to cardiovascular health.     

Belgian (Chinese herb) nephropathy: why?

During the last years several patients with renal failure were admitted in Brussels hospitals. The progressive interstitial fibrosis with tubular atrophy seen in these patients has been ascribed to the slimming therapy preceding the pathology. The nephropathy was remarkable with regard to its extensive fibrotic process and the rapidity of its evolution. The ingestion of Aristolochia fangchi instead of the prescribed Stephania tetrandra, one of the components of the slimming therapy, was put forward as hypothesis for the etiology of the nephropathies in the literature. Questions however remain unanswered: Why have certain persons, among thousands similarly treated including ingestion of Aristolochic acids, not withstood the treatment? Why is there no correlation between the length of treatment and the occurrence nor the degree of illness? Last but not least: Is it in the actual conditions possible to be confident again in slimming treatments as the concerned one? We made an overview of the pharmacological action and possible (nephro) toxicity of the known components of the concerned therapy. Concerning the Chinese plants we have described and commented on the procedures for quality control actually at disposal and the difficulties in differentiation between resembling species and possible substitute herbs. We have described largely the traditional and medicinal use of the involved Chinese plants as to evaluate their implication in the nephrotoxicity. The elements of the therapy possibly relevant in the etiology of the disease are mentioned. The overview shows that different elements of the therapy are hazardous. Attention is caught to the danger of the use of (Chinese) herbs of unknown origin when nor the indications nor the form of preparation--in this case decoctions--are respected and when the quality cannot be assured, due to lack of (official) operating procedures. Medicinal plants as those implied contain secondary metabolites (bis)-benzylisoquinoline-alkaloids, dihydroxy-diallyl-biphenyls, aristolochic acids) with strong pharmacological (and possibly toxic) actions. Attention is caught to the danger of alternative therapies as mesotherapy. Products are injected which are not proved safe for this administration way. The administration during long periods of cocktails with anorectics (fenfluramine and diethylpropion) in association with a diuretic, a tranquilizer, plants with laxative and atropinergic action are alike to be at the origin of susceptibility in the excretion system. Under these circumstances exposure to any toxic product might cause renal failure. Several years have passed after the scientific reports of the first nephropathy cases in Belgium. We are afraid that prohibiting (temporarily) three Chinese herbs (Stephania tetrandra, Aristolochia fangchi and Magnolia officinalis) does not provide enough safety in order to assume responsibilities for common health care. Keeping in mind that these treatments were not meant to cure any disease but only for slimming, we ask Belgian authorities to regulate strictly the use of (Chinese) herbal medicines, the products and practices in alternative practices as mesotherapy and cocktail-treatments.     

Hookworm infection and disease: advances for control

Advances in epidemiology and in control strategies of hookworm infection and associated disease were reviewed. Recent estimates indicate that hookworms infect approximately 1.3 billion people worldwide, and 96 million suffer from associated morbidity, including also insidious effects on nutritional status and on physical and intellectual development. Recent research studies on iron loss and iron-deficiency anaemia associated to hookworm infection were irondeficiency anemia associated to hookworm infection were reviewed. Recommendations for planning strategies for the control of hookworm infection were addressed and epidemiology, targets, chemotherapy, health education, sanitation, monitoring and evaluation in helminth control programmes were discussed. Special relevance was given to chemotherapy with new, single dose broad spectrum, safe anthelminthic drugs as the mainstay of control strategy to reduce intensity of infection, iron-deficiency anaemia and other morbidity indicators associated with hookworm infections. For the control of transmission of hookworm infection, periodic chemotherapy should be implemented in the context of ongoing improvement of sanitation and promotion of health education. These elements should be integrated into the prevailing system of primary health care and must be based on multisectoral collaboration to ensure sustainability of control programmes.     

Aristolochic acids, aristolactam alkaloids and amides from Aristolochia kankauensis

Fourteen aristolochic acid derivatives: ariskanins A-E, 3-hydroxy-4-methoxy-10-nitrophenanthrene-1-carboxylic acid methyl ester, aristolochic acid-II methyl ester, aristolochic acid-IV methyl ester, aristolochic acid-C, -I, -II, -III, -IV, -IVa; nine aristolactam alkaloids: aristolactam, aristolactam-AII, -BIII, -AIII, -III, cepharanone-A, 9-methoxy-aristolactam-I, aristolactam-N-beta-D-glucoside and aristolactam-C-N-beta-D-glucoside; a 4,5-dioxoaporphine alkaloid: cepharadione-A, together with 12 other compounds: methyl-p-coumarate, N-trans-feruloyltyramine, N-cis-feruloyltyramine, methyl vanillate, methyl paraben, allantoin, an octadecyl- and eicosyl ferulate mixture, cis- and trans-p-coumaric acid, N-p-coumaroyltyramine, N-p-cis-coumaroyltyramine, methyl ferulate and isorhamnetin-3-O-rutinoside were isolated and characterized from the fresh root and stem of Aristolochia kankauensis. Their structures were elucidated by spectral and chemical methods. Among them, ariskanins-A-E and N-p-cis-coumaroyltyramine are reported for the first time from a natural source. The cytotoxicity and antiplatelet activity of the compounds isolated are also discussed.     

The effects of anemia on heme synthesis parameters during lead exposure

The effects of anemia during lead exposures were studied using an infant baboon animal model. When the hemoglobin concentration was reduced to less than 70% of normal, a marked blood lead increase was observed and the free erythrocyte porphyrin value, aminolevulinic acid dehydratase activity and reticulocyte counts increased. Special emphasis should be placed on nutritional effects in lead exposures.     

Fatal pulmonary fat embolism after dorsal spinal fusion

OBJECTIVE: To determine whether health shop staff give specific therapeutic recommendations to someone who describes symptoms associated with serious pathology and to determine whether they refer this person to conventional medical care. DESIGN: Quantitative survey using participant observation. SETTING: Health food shops selling herbal, homeopathic or nutritional remedies in inner London. METHOD: A researcher visited 29 health food shops and claimed to be suffering from severe, daily headaches of recent onset. The researcher recorded on tape whether the health shop staff took diagnostic information; recommended any therapeutic intervention; asked about or recommended seeing a general practitioner (GP); asked about use of conventional drugs. Coding of the interactions was carried out independently by two researchers. RESULTS: Whereas all but two shops recommended a specific therapeutic intervention, less than one in four advised a GP consultation. Forty-two different interventions were recommended. There was little consistency in the advice given. CONCLUSION: Health food shops need to review the circumstances in which they should venture to provide advice and the basis on which they make any therapeutic recommendations. Shops selling over-the-counter herbal, homeopathic and health food products are a common feature of UK high streets. Such shops could be a useful source of health information and advice to their customers, but could also lead to harm, for example by delaying treatment of known benefit, if their recommendations were to be inaccurate or inappropriate.     

Development of drug delivery systems for macromolecular drugs

With a rapid progress in biotechnology, a variety of endogenous macromolecular substances have become a novel class of therapeutic agents. This review will focus on the development of delivery systems for macromolecular drugs. Current status and future perspectives in this research field are reviewed mainly based on the results obtained in our laboratory. First of all, we studied pharmacokinetic characteristics of macromolecules in relation to their physicochemical properties such as molecular weight and electric charge. Based on this information, we first developed macromolecular prodrugs as a delivery system for low molecular weight drugs. An antitumor antibiotic, mitomycin C (MMC) were covalently conjugated with dextran and various types of macromolecular prodrug of MMC were developed for tumor targeting. Secondly, delivery systems for protein drugs such as soybean trypsin inhibitor, uricase, and recombinant superoxide dismutase (SOD) were developed. In particular, successful targeting of SOD to the liver, kidney and blood circulation was achieved by chemical modification of the protein drug. Finally, we have been trying to develop delivery systems for nucleic acid drugs involving antisense oligonucleotides and plasmid DNA. Prior to the development of delivery systems, we found that the pharmacokinetics of the nucleic acid drugs are decided by their physicochemical properties as polyanions even if these materials contain genetic information. Several approaches were tested to control the in vivo behavior of the oligonucleotides and plasmid DNA based on the finding. Thus, we have established the strategy for rational design of delivery systems for various types of macromolecular drugs based on the pharmacokinetic considerations. This methodology can be a formidable tool for the development of clinically applicable macromolecular drugs.     

Effect of selected antimutagens on the genotoxicity of antitumor agents

Cyclophosphamide (CP), bleomycin (BL), doxorubicin (DOX) and cisplatin (CISP) are potent antitumor drugs used worldwide against many forms of human cancer. As with most such agents, there can be physiological side-effects and the possible induction of mutations and other genotoxic effects in non-tumor cells. It is common for patients to ingest a host of food supplements to diminish the discomforting side-effects of therapy. Because these food supplements are often also rich in antimutagens that could also affect the biological efficacy of the antitumor drugs, we investigated if such antimutagenic agents were indeed antimutagenic to these antitumor drugs. Using the Salmonella/microsome bioassay, we tested CP, BL, DOX, and CP for mutagenicity in the presence and absence of the antimutagens ascorbic acid (AA), chlorophyllin (CHL) and (+)-catechin (CAT). AA was a very effective antimutagen against CISP and less effective against BL and DOX. It was not antimutagenic to CP. CHL was effective as an antimutagen against all four antitumor drugs, and CAT was a strong inhibitor of DOX mutagenicity, but had little effect on BL, CP and CISP. These data now provide a basis for future in vivo antitumor/antimutagen combination studies to determine if these antimutagens function in a manner to reduce genetic effects without having concomitant effects on intended antitumorogenicity of these therapeutic agents.     

An unusual congenital nail dystrophy (''soft nail disease'')

Approximately 4,000 preschool black children from low-income families in South Memphis participated for three years in a supplementary food program sponsored by the US Department of Agriculture. Part of this group received additional benefit from food stamps, day-care centers, and an infant-feeding program. We evaluated the effects of this participation in 250 children selected randomly from the enrollment list of the supplemetary program. Each child was examined for height, weight, head circumference, and levels of hemoglobin, serum iron, and vitamins A and C. The data were then compared with those from a similar survey in the same area conducted three years before. The results of this comparison indicate considerable improvements in height and weight and a reduction in the incidence of anemia and in the numbers of children with low plasma vitamin A levels. In the absence of other recognizable intervening factors, we conclude that federal food assistance programs were primarily responsible for the observed nutritional improvements.     

Food intakes of adult Melbourne Chinese

Food intake patterns of 545 adult Melbourne Chinese were studied in 1988 and 1989 using a 220-item food-frequency questionnaire appropriate for Chinese eating practices. Men and women were compared, adjusting for age, time in Australia and education. Men consumed more rice and alcoholic beverages as energy. In women, the energy intake was derived from foods of traditional Chinese types. There were two types of consumption patterns: in the first group were those who acculturated towards an Australian way of eating by replacing some traditional Chinese foods, such as rice, pork, leafy green and cruciferous vegetables, soups and tea, with 'new foods', such as wheat products, red meats and coffee; in the second were those who limited their intake to a handful of traditional Chinese foods as the major source of energy. The educated, the professional and those with an administrative profession, the Australian-born and those with a longer length of stay fitted into the first group, and were more acculturated towards Australia than those born in the People's Republic of China or Vietnam and who migrated at an older age. The first group may benefit from the best of both worlds, but may risk the diseases of an industrialised society. The second group may be trapped at a cultural crossroads and may be unable to make appropriate food choices. Public health efforts in Australia, where one in every five is overseas-born, should provide for nutrition and health education for new and aged migrants of non-European cultural backgrounds.     

Characterization of recombinant type II collagen: arthritogenicity and tolerogenicity in DBA/1 mice

Using new nonisotopic and isotopic methods, we showed previously that fatty acid synthesis was markedly stimulated in weight-stable normal volunteers by a very-low-fat formula diet with 10% of energy as fat and 75% as short glucose polymers. In this study, we determined whether fatty acid synthesis was equally stimulated by a very-low-fat solid diet made with foods consumed typically. Four normal volunteers consumed the same very-low-fat formula diet for 25 d and then an isoenergetic solid food diet with 10% of energy as fat and 75% as starch, simple sugars, and fiber for 25 d. To measure fatty acid synthesis, the fatty acid compositions of the diets were matched to the composition of each subject's adipose tissue and compared with the composition of VLDL-triacylglycerol. In all subjects, the large increases in newly formed palmitate and decreases in linoleate in VLDL-triacylglycerol were quickly reversed by the solid food diet, and the fraction of de novo synthesized fatty acids in fasting VLDL-triacylglycerol decreased from 30-54% to 0-1%. In a second group of subjects, the stimulation of fatty acid synthesis by the formula diet with 75% glucose polymers was similarly reduced by a formula diet with amounts of fat, starch, and sugar chosen to mimic those of the solid food diet, but persisted after the addition of fiber or a diet with 75% sugar. In conclusion, an increase in fatty acid synthesis and palmitaterich, linoleate-poor VLDL-triacylglycerol induced by very-low-fat, high-sugar diets may be reduced by the substitution of dietary starch for sugar with potentially beneficial effects on cardiovascular health.     

Running and addiction: Precipitated withdrawal in a rat model of activity-based anorexia.

Exercise improves cardiovascular health, strengthens muscles and bones, stimulates neuroplasticity, and promotes feelings of well-being. However, when taken to extremes, exercise can develop into an addictive-like behavior. To assess the addictive potential of exercise, withdrawal symptoms following injections of 1.0 mg/kg naloxone were compared in active and inactive male and female rats. Active and inactive rats were given food for 1 hr or 24 hr/day. Additionally, a group of inactive rats was pair-fed the amount of food consumed on the previous day by food-restricted active rats. Rats fed for 1 hr/day decreased food intake and lost weight. Additionally, food-restricted active rats increased wheel running. There was a direct relationship between the intensity of running and the severity of withdrawal symptoms. Active food-restricted rats displayed the most withdrawal symptoms, followed by active rats given 24-hr access to food. Only minimal withdrawal symptoms were observed in inactive rats. These findings support the hypothesis that exercise-induced increases in endogenous opioid peptides act in a manner similar to chronic administration of opiate drugs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structural features associated with reactive metabolite formation in clozapine analogues

Clozapine is associated with a high incidence of agranulocytosis. We had previously found that it is oxidized by granulocytes, or simply HOCl, to a reactive metabolite that irreversibly binds to the cells, and we proposed that this reactive metabolite is responsible for clozapine-induced agranulocytosis. The reactive metabolite appeared to be a nitrenium ion formed by chlorination of the nitrogen bridge between the two aromatic rings. If this is correct, analogs that contain this structural feature should also be oxidized to a reactive intermediate while those not possessing this feature would, at least, not form the same type of reactive intermediate and, therefore, may not induce agranulocytosis. We tested the first part of this hypothesis with three clozapine analogs that do contain a nitrogen bridge and three that do not. Consistent with the hypothesis, the three analogs that do contain the nitrogen bridge formed reactive intermediates that could be trapped with glutathione when oxidized by HOCl, myeloperoxidase or activated neutrophils. In contrast, we found no evidence of a reactive intermediate on oxidation of analogs that contained an oxygen or sulfur bridge rather than a nitrogen bridge. If such reactive metabolites are responsible for drug-induced agranulocytosis, it should be possible to use such a simple screening method to test drugs at an early stage in their development for the potential to induce agranulocytosis.     

Ultraviolet inactivation of the midi variant of Qbeta-RNA. Determination of quantum yield and lesions produced

The Chinese restaurant syndrome consists of a characteristic symptom complex, with limited times of onset and duration after eating in a Chinese restaurant. There is widespread belief that the C.R.S. is due to monosodium glutamate used in preparing food in Chinese restaurants and that as many as 25 per cent of the general population may be susceptible to the syndrome. Questionnaires were developed to determine the unpleasant symptoms which 530 subjects associated with specific foods, eating places, and "ethnic" styles of preparing food. Over 90 per cent of respondents associated unpleasant symptoms with specific foods, but only 6.6 per cent experienced an event which would "possibly" represent the characteristic C.R.S. Nevertheless, when the phrase "Chinese restaurant syndrome" was introduced in a second questionnaire, 31 per cent of respondents believed that they were personally susceptible to it. Many people do experience unpleasant symptoms after eating, and particularly after eating food associated with a different culture. Although the responses to food symptomatology questionnaires represent an important aspect of the sociology of eating behavior, this procedure should not be considered an objective data collecting system.     

Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy

Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the development of radiation nephropathy after BMT. In previous BMT nephropathy studies, ACE inhibitor therapy was started pre-BMT and continued indefinitely. In preparation for clinical trials, studies were designed to determine whether effective prophylaxis could be achieved if ACE inhibitor therapy was started after engraftment, and to determine whether ACE inhibitors needed to be given indefinitely. The present studies in our rat syngeneic BMT model showed that captopril therapy started 25 days post-BMT was as effective as therapy started prior to BMT. When ACE inhibitor therapy was discontinued 28 weeks after BMT, the protective effect was not lost if adequate control of azotemia had been maintained for 26 weeks. If adequate control of azotemia was not maintained for 26 weeks, BMT nephropathy progressed rapidly when ACE inhibitor therapy ended, and slowly when it was continued. Failure to control azotemia was a better predictor of renal failure than failure to control hypertension or proteinuria. Based on these preclinical studies, it would appear that ACE inhibitor therapy will be effective in the prophylaxis of BMT nephropathy even if begun after engraftment, and that ACE inhibitors may not need to be given indefinitely.     

Studies of the elderly in Boston. I. The effects of iron fortification on moderately anemic peole

It has been reported that large numbers of elderly Americans are moderately anemic because of iron deficiency anemia. In the present study, information has been obtained concerning blood composition, health, and nutritional habits of 779 people over 60 years of age, institutionalized or free-living in the Boston area. This paper presents the results of their blood examinations. Two hundred twenty-one of the free-living people examined who showed hemoglobin levels between 9 and 12.9 g/dl agreed to participate in an iron fortification study. Two-thirds of them received iron-fortified grain products daily for 6 to 8 months. The rest received the same foods without added iron. At the end of the experimental period a marked increase in hemoglobin levels averaging 1.4 g/dl was observed in both groups. This appeared to be attributable to an undefined intervention effect; no measurable effects attributable to the iron fortification were observed. Three months of daily ferrous sulfate administration to those whose hemoglobin levels remained below 13 g/dl was without effect. Examination of the data obtained suggests that the cause of the moderately low hemoglobin levels initially observed was not occult bleeding or folic acid or iron deficiency.     

Food, mood and health: a neurobiologic outlook

Hippocrates was the first to suggest the healing power of food; however, it was not until the medieval ages that food was considered a tool to modify temperament and mood, although scientific methods as we know them today were not in use at the time. Modern scientific methods in neuroscience began to emerge much later, leading investigators to examine the role of diet in health, including mental wellbeing, with greater precision. This review shows how short- and long-term forced dietary interventions bring about changes in brain structure, chemistry, and physiology, leading to altered animal behavior. Examples will be presented to show how diets alter brain chemistry, behavior, and the action of neuroactive drugs. Most humans and most animal species examined in a controlled setting exhibit a fairly reproducible pattern of what and how they eat. Recent data suggest that these patterns may be under the neurochemical and hormonal control of the organisms themselves. Other data show that in many instances food may be used unconsciously to regulate mood by seemingly normal subjects as well as those undergoing drug withdrawal or experiencing seasonal affective disorders and obesity-related social withdrawal. We will discuss specific examples that illustrate that manipulation of dietary preference is actually an attempt to correct neurochemical make-up.     

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red-cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.