[Studies on protective effect of total flavonoids of Astragalus on liver damage induced by paracetamol].

OBJECTIVE: To study the protective effect of total flavonoids of Astragalus (TFA) on the liver against large doses of paracetamol in mice. METHOD: After oral administration of TFA or Vitamin C 1 h prior to giving large dose of paracetamol in mice, the changes of paracetamol-induced mortality rate, serum enzyme level and liver damage degree were observed. RESULT: Paracetamol produced 80% mortality, within 24 hours of the administration of a dose of 1000 mg.kg-1 to the mice. Pre-treatment of the animals with TFA (100 mg.kg-1) or Vitamin C (1,000 mg.kg-1) reduced the death rate to 20% and 0% respectively. There was also a significant rise in the serum enzyme level of alanine transaminase (P < 0.001) and the area of liver necrosis (P < 0.001), 24 h after paracetamol (400 mg.kg-1) treatment. With pre-treatment with either TFA or Vitamin C, there was an obvious dose-dependent decrease in ALT levels and the area of hepatocellular necrosis. CONCLUSION: TFA has potential protecting effect against the paracetamol-induced hepatic damage.

[Protection against paracetamol-induced hepatic damage using total flavonoids of Astragalus].

OBJECTIVE: To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol-induced hepatic damage. METHOD: Analysing paracetamol and its metabolites in mice urine by HPLC and studying the mechanism of anti-damage induced by paracetamol using experiment module of pentobarbital-induced sleeping time. RESULT: Administration of large doses of paracetamol to C57BL/6J mice produced significant hepatic injury with marked elevation in serum ALT activity and severe hepatocellular necrosis. TFA showed a good protective capability against paracetamol-induced hepatic injury. TFA had no marked effect on paracetamol and its metabolites except for the mercapturate-conjugate. The concentration of mercapturate change decreased with increasing TFA dose. TFA had no effect on the pentobarbital metabolites (P > 0.05). However, paracetamol (400 mg.kg-1) prolonged the sleeping time (by 110 min relative to the controls, P < 0.001). The TFA (P < 0.005) caused significant reduction in paracetamol-prolonged pentobarbital-induced sleep. CONCLUSIONS: The mechanism of TFA's protective effect against the paracetamol-induced damage may be related to the inhibition of some metabolism progress of paracetamol and the reduction of the toxicity metabolite such as mercapturate-conjugate.

Toxicity of complementary therapies: an eastern perspective.

Chinese traditional medicine is used extensively in Chinese populations, and other Asian countries employ similar therapies. Herbal treatments have a major role in these systems, and although most have a well-established safety record, occasional adverse effects are seen. Problems arise when toxic herbs are used in excessive doses, with improper preparation, or when they are substituted erroneously. There may also be adulteration with Western drugs or heavy metals, and interactions between herbs and Western drugs may also occur. It is always prudent to obtain a complete history of the use of herbal medications during any clinical assessment, particularly in Asian patients.

Alternative therapies and medical science: designing clinical trials of alternative/complementary medicines--is evidence-based traditional Chinese medicine attainable?

Evidence-based traditional Chinese medicine is attainable. With good planning and a positive attitude, the remedies used in traditional Chinese medicine (TCM) and Chinese proprietary medicines can be studied at a standard acceptable to modern science. The identification of an active principal should not delay the search for effective remedies from the TCM pharmacopoeia. Herbal mixtures can be validly tested to establish their efficacy. Problems with potential batch-to-batch variation can be circumvented by appropriate randomization. Subsequent independent screening and randomization to treatment and placebo arms can allow for the individualization of treatments by TCM practitioners. However, clearly defined treatments are required and should be recorded in a manner that enables other suitably trained researchers to reproduce them reliably (e.g., using prescriptions in Chinese). Quality control of TCM is a prerequisite of credible clinical trials. Correct natural ingredients must be used without adulteration or erroneous substitution. Evidence of safety in man is essential, and in lieu of data from formal toxicity studies, clear, convincing, and impartial evidence of safety is needed based on their long-term use in mainstream TCM practice backed up by publications in the Chinese medical/scientific literature.

The relationship between upper gastrointestinal hemorrhage and drug use: a case control study.

The relationship between upper gastrointestinal hemorrhage and drug use was studied in 251 Chinese patients (179 men, 72 women) admitted to the Prince of Wales Hospital, Hong Kong, and control subjects matched for age and sex. There was a highly significant difference between the cases and control subjects in the use of NSAIDs (odds ratio 14.0, p < 0.00001), ulcer healing drugs (odds ratio 12.5, p < 0.00001), and Chinese proprietary medicines (odds ratio 16.0, p < 0.00001). There was also a significant difference in the use of analgesics (odds ratio 14.0, p = 0.001), paracetamol (odds ratio 2.5, p = 0.01), antacids (odds ratio 2.7, p < 0.001) and unknown drugs (odds ratio 4.7, p < 0.001). Cases also differed from control subjects regarding the use of tobacco (odds ratio 2.3, p < 0.001) and alcohol (odds ratio 1.7, p = 0.02), and the presence of peptic ulcer symptoms (odds ratio 29.8, p < 0.00001). Significantly more control subjects than cases were receiving aspirin, cardiovascular drugs, bronchodilators, oral hypoglycemic drugs/lipid-lowering drugs, and anticonvulsants/hypnotics, due to the inevitable differences in disease pattern between the 2 groups. NSAID use was a major factor associated with upper gastrointestinal hemorrhage from primarily peptic ulcers. Differences in the use of other drugs may reflect variations in disease patterns between cases and controls, the common practice of self-medication in Hong Kong, and the concomitant use of NSAIDs and ulcer healing drugs/antacids.

Usage and adverse effects of Chinese herbal medicines.

The great majority of Chinese herbal preparations are safe, and in the past, some useful Western drugs have been derived from these herbs. Nearly all serious poisonings are due to the few preparations containing aconitine, podophyllin or anticholinergics or else proprietary preparations containing dangerous Western drugs or heavy metals. Both medical professionals and the general public should be alerted to the potential toxicity of herbal remedies. There should be frequent monitoring of Chinese herbal medicines or their derivatives, such as some Chinese proprietary medicines, for undeclared Western drugs and heavy metals. Mothers should be discouraged from treating their children with herbal or proprietary medicines. There should be continuing efforts to collect safety information on these widely used products.

Neurotoxicity following the ingestion of a Chinese medicinal plant, Alocasia macrorrhiza.

1. A case of poisoning due to the raw root tuber of a Chinese medicinal plant, Alocasia macrorrhiza is presented. 2. The patient developed neurological (severe pain and numbness in the perioral area and throat) and gastrointestinal (nausea, vomiting, abdominal pain) symptoms immediately after eating the root tuber. 3. A macrorrhiza has properties and morphology very similar to another medical plant. A. odora. The root tuber of the latter is known to contain a neurotoxin sapotoxin.

Poisoning due to Chinese proprietary medicines.

1. To determine the toxic potentials of those Chinese proprietary medicines (CPM) which are commonly used for self-poisoning by adults in Hong Kong, all patients admitted to four of the eight general medical wards at the Prince of Wales Hospital between January 1988 and December 1993 were retrospectively studied. 2. There were 54 women and 17 men with their age ranging from 15 to 86 years. Twenty-three subjects (32%) also took alcohol, chemicals or drugs. Of the 51 subjects (72%) who had taken topical medicaments, 22 had no symptoms while 28 had minor features of gastrointestinal irritation (n = 26), mild (n = 2) or severe (n = 1) salicylate poisoning. Of the 17 subjects (24%) who had taken CPM tablets/capsules, nine had mild symptoms including nausea/vomiting and drowsiness. The three remaining patients (4%) who had ingested liquid CPM preparations were asymptomatic. Elevated plasma salicylate or paracetamol concentrations (> 0.1 mmol l-1) were found in some patients who had taken topical medicaments and CPM tablets/capsules, respectively. All the 71 patients completely recovered. 3. Most of the CPM used for self-poisoning in Hong Kong were of low to moderate toxicity except for those containing wintergreen oil (methyl salicylate).

The effect of transcutaneous electrical nerve stimulation (TENS) on autonomic cardiovascular reflexes.

Transcutaneous electrical nerve stimulation (TENS) has been shown to have an anti-ischaemic effect in patients with angina and peripheral vascular disease that appears to be additional to any analgesic action. The mechanism for this anti-ischaemic effect is not known but it is possible that TENS interferes with the autonomic responses to ischaemia. To determine if TENS has any direct action on autonomic reflexes we have assessed the effect of high frequency TENS on a variety of standard tests of autonomic cardiovascular reflexes in 10 normal subjects. Tests were done on four consecutive days at the same time and TENS therapy or placebo was randomly allocated on 2 days each. Results of the tests were assessed by one person 'blinded' to the randomization order. These showed that TENS was associated with a significant reduction in the rise of the diastolic blood pressure (21.8 +/- 2.3 v. 17.6 +/- 17 mmHg; p < 0.05) during isometric exercise, using sustained Handgrip. There was no significant effect discernible on the changes of heart rate and blood pressure during the Valsalva manoeuvre, cold face stimulus or head-up tilt. Transcutaneous electrical nerve stimulation appears, therefore, to have a mild inhibitory action on those reflexes mediated predominantly by the sympathetic nervous system and this is more apparent when the stimulation may be greater, as during isometric exercise.

Poisoning due to an over-the-counter hypnotic, Sleep-Qik (hyoscine, cyproheptadine, valerian).

The clinical features and risk of hepatotoxicity of 'Sleep-Qik' (valerian dry extract 75 mg, hyoscine hydrobromide 0.25 mg, cyproheptadine hydrochloride 2 mg) were determined in 23 patients treated in our hospital between 1988 and 1991. The main clinical problems were central nervous system depression and anticholinergic poisoning. There was no clinical evidence of acute hepatitis in the 23 patients after taking an average of 2.5 g of valerian (range 0.5 to 12 g). There was no evidence of subclinical liver damage in 12 patients who had routine liver function tests performed approximately 6-12 hours after ingestion. Delayed onset of severe liver damage was excluded in 10 patients in whom a telephone follow-up was possible. However, subclinical liver dysfunction in the acute stage (onset after 12-24 hours) and in the intervening period after discharge from hospital could not be excluded. To establish the risk of hepatotoxicity in long-term users and in those taking an overdosage of valerian, a much larger study of longer duration with serial liver function tests is clearly needed.

Poisoning by Chinese herbal medicines in Hong Kong: a hospital-based study.

The harmful effects of some Chinese herbal medicines (CHM) have become a cause for concern among the medical profession and the general public in Hong Kong. From 1989 to 1993, at least 33 patients were treated in the Prince of Wales Hospital because of severe poisoning by CHM. Of these, 20 presented with clinical features typical of aconitine poisoning following the ingestion of "chuanwu", the main root of Aconitum carmichaeli, or "caowu", the root of Aconitum kusnezoffii. Strict legislation controlling the use of chuanwu and caowu alone would have prevented many of the severe poisonings by CHM in Hong Kong.

Aconitine poisoning due to Chinese herbal medicines: a review.

Both "chuanwu", the main root of Aconitum carmichaeli, and "caowu", the root of A kusnezoffii, are believed to possess anti-inflammatory, analgesic and cardiotonic effects and have been used in Chinese materia medica mainly for the treatment of musculoskeletal disorders. They contain the highly toxic C19 diterpenoid alkaloids of aconitine, mesaconitine and hypaconitine. After ingestion, patients may present with signs and symptoms that are typical of aconitine poisoning. Death may occur from ventricular arrhythmias, which are most likely to occur within the first 24 h. Management of aconitine poisoning is essentially supportive. There are no adequate studies in humans to indicate the most effective treatment of the ventricular arrhythmias. All clinicians should be alerted to the potential toxicity of "chuanwu" and "caowu".

Adverse reactions to intravenous N-acetylcysteine in Chinese patients with paracetamol (acetaminophen) poisoning.

The incidence of adverse reactions to intravenous N-acetylcysteine (NAC) was studied in 56 Chinese patients with paracetamol (acetaminophen) poisoning. Eight (14%) patients developed a skin rash (n = 7) or fever (n = 1) mostly during the initial high dose infusion of the antidote. In four subjects (three with toxic plasma paracetamol levels), the infusion was continued without a worsening of the adverse reaction. NAC was discontinued in the remaining four subjects in whom the paracetamol levels were subsequently found to be non-toxic. Intravenous chlorpheniramine was given to six subjects. All eight subjects completely recovered. In the dose that is recommended for the treatment of acute paracetamol poisoning, intravenous NAC is generally safe in Chinese but mild side effects are common. We recommend that the initial loading dose is given over 60 rather than 15 min.

Drug overdosage and other poisoning in Hong Kong--the Prince of Wales Hospital (Shatin) experience.

From 1988 to 1991, 732 patients (91.1% Chinese) were admitted to four general medical wards at the Prince of Wales Hospital in Hong Kong with acute poisoning. The patients were predominantly female (68.9%) and relatively young (86.3% below the age of 40). Further analysis of 655 patients indicates that the vast majority of patients (96%) were admitted after self-poisoning with drugs or chemicals while 4% of cases were due to accidental poisoning. The main agents used by the former group included hypnotics/sedatives (33.1%), household products (15.7%), and analgesics (13.7%). There were nine deaths (1.4%). When compared to other Western countries, two important variations in the pattern of acute poisoning were seen. A substantial proportion of drugs ingested by our patients were not precisely identified. 'Dettol', a household product, was commonly used for self-poisoning in Hong Kong. Territory-wide studies of longer duration are needed to provide the physicians in Hong Kong with much needed information on the incidence and the pattern of acute poisoning.

Herb-induced aconitine poisoning presenting as tetraplegia.

Both "chuanwu", the main root of Aconitum carmichaelii, and "caowu", the dried root of Aconitum kusnezoffii or other members of the Aconitum genus, have long been used in Oriental materia medica to treat rheumatism, arthritis, bruises, fractures and cardiac complaints. These herbs contain the highly toxic diterpene alkaloids aconitine, mesaconitine and hypaconitine. A case of aconitine poisoning due to chuanwu and caowu that is described presented as profound tetraplegia.

The spectrum of poisonings in Hong Kong: an overview.

Poisoning is an important health problem in Hong Kong. In 1990 alone, 6500 patients were treated in Hong Kong hospitals and there were 245 deaths. Two hospital-based studies indicated that exposures to poisons were intentional in the majority (96%) of adult cases, with hypnotics/sedatives (34%), household products (16%) and analgesics (14%) being most often used. Apart from drugs and chemicals, accidental poisoning may occur after the ingestion of Chinese medicines or vegetables contaminated with methamidophos. The former may contain highly toxic aconitine or podophyllin, declared and undeclared western drugs such as phenylbutazone and aminopyrine, and heavy metals. It is important that there be a continuing effort to collect information on the factors leading to and the pattern of poisonings in Hong Kong and other Southeast Asian countries. This is particularly valuable for childhood poisoning so that appropriate preventive measures can be taken.

Chinese herbal medicines revisited: a Hong Kong perspective.

Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) are widely used by people of Chinese origin throughout the world. Although the use of these medicinal materials rarely causes significant toxic effects, cases of severe and even fatal poisoning have occurred after medication with herbs containing aconitine, podophyllin, and anticholinergic substances. Furthermore, CHM and CPM are often adulterated with substituted herbs, heavy metals, and western medicines; such contamination can have important clinical consequences. In Hong Kong, surveillance and legislation are required to control the use of some of these herbal preparations. In other countries, medical practitioners should also be aware of the possibility that these herbal-medicine-related remedies may cause significant clinical problems in their Chinese patients.