Wing-Tat Poon

Identification of a novel vardenafil analogue in herbal product

A new herbal health product marketed for enhancing erectile function, namely Power58 Platinum, was purchased over-the-counter in Hong Kong. The product was tested for adulteration with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. A new analogue of vardenafil, in which the N-ethylpiperazine ring and the sulphonyl group were removed from the vardenafil structure, was identified in the product.

Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine.

Fructus Psoraleae (FP) is used by herbalists for the treatment of postmenopausal osteoporosis, vitiligo, and psoriasis. It is used alone, or in combination with other herbs, in some countries in the form of proprietary medicine. It is recognized as one of the emerging hepatotoxins and here we report three cases of acute hepatitis after exposed to FP and its related proprietary medicine. It seems possible that psoralen and its related chemicals may be responsible for the hepatotoxicity. Decoction with other herbs may result in higher concentration of toxic constituents and in more severe liver injury. In summary, FP is associated with hepatotoxicity in some individuals. Pharmacovigilance for the potential side effects of herbal products is necessary.

Risk of Vitamin A Toxicity From Candy-Like Chewable Vitamin Supplements for Children

Numerous vitamin supplements are available over-the-counter to the general public. Some such supplements are available as candy-like chewable preparations to encourage consumption by children. We report 3 cases of overdose of such preparations. Each patient had taken an estimated 200000 to 300000 IU of vitamin A. Their circulating vitamin A (retinol and retinyl palmitate) concentrations were monitored over a 6-month period. There were no clinical or biochemical complications noted. However, there were marked increases in both retinol and retinyl palmitate concentrations above age-related reference ranges. In particular, it took 1 to 3 weeks for the serum retinol concentrations to peak and many months for them to normalize. Parents should be warned about the dangers of excessive vitamin consumption. Clinicians should be aware of the late peak in serum retinol concentrations, which may lead to late complications of vitamin A overdose.

Nitrite-induced methaemoglobinaemia - aetiology, diagnosis and treatment.

A 41‐year‐old woman presented with the clinical features of methaemoglobinaemia after drinking Chinese herbal medicine. A life threatening methaemoglobin level of 68% was measured. Both clinical and laboratory diagnostic difficulties were encountered. The pitfalls of pulse oximeter, blood gas analysis and co‐oximeter interpretation during diagnosis and after methylene blue administration are discussed.

Aconite poisoning over 5 years: a case series in Hong Kong and lessons towards herbal safety.

AbstractBackground: Aconite poisoning is a severe, life-threatening poisoning related to the use of traditional Chinese medicine (TCM). Despite current legislation, repeated poisoning cases are steadily encountered. Objective: The aim of the study was to summarize the clinical features and to elucidate the causative and contributory factors leading to aconite poisoning. Methods: This study was conducted within the Hospital Authority Toxicology Reference Laboratory, which is the sole tertiary referral clinical toxicology laboratory in Hong Kong. This retrospective study reviewed all confirmed aconite poisoning cases handled by a clinical toxicology laboratory between April 2004 and July 2009. The diagnosis in all cases was confirmed biochemically by detecting aconitum alkaloids in urine specimens. Additionally, herbal specimens were morphologically identified and herbal formulae were studied and transcribed. The cause of poisoning for each case was determined whenever possible. Results: Fifty-two cases were examined in this aconite poisoning case series. Neurological, cardiovascular and gastrointestinal toxicities were encountered in 49 (94.2%), 46 (88.5%) and 31 (59.6%) patients, respectively. The poisoning was severe in 6 (11.5%) patients, moderate in 17 (32.7%) patients and mild in 29 (55.8%) patients. Amongst 44 patients (84.6%) in whom the underlying reasons of poisoning could be determined, four major causes were found. These included overdose- prescription of a higher than recommended dosage of aconite herbs in 17 (32.7%) cases; ‘hidden’ poisoning (the aconite herb was not prescribed but dispensed inadvertently) in 17 (32.7%) cases; usage of inadequately processed herbs in 7 (13.5%) cases; and dispensary error in 2 (3.9%) cases. No case fatality was recorded. Conclusion: In the majority of cases in this series, the causes of poisoning can be traced to poor-quality herbs, poor quality of prescription practice, or dispensary errors. The quality issues of TCM practice should be critically addressed to minimize this poisoning threat.

Fatal viral infection-associated encephalopathy in two Chinese boys : a genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variants

Influenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele [p.Phe352Cys; p.Val368Ile] were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0+C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of [p.Phe352Cys; p.Val368Ile] among Hong Kong Chinese was 0.104, similar to Japanese data, and [p.Phe352Cys] has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE.

Quantification of Aristolochic Acid-Derived DNA Adducts in Rat Kidney and Liver by Using Liquid Chromatography-Electrospray Ionization Mass Spectrometry

Aristolochic acid (AA), derived from the herbal genus Aristolochia and Asarum, has recently been shown to be associated with the development of nephropathy. Upon enzyme activation, AA is metabolized to the aristolactam-nitrenium ion intermediate, which reacts with the exocyclic amino group of the DNA bases via an electrophilic attack at its C7 position, leading to the formation of the corresponding DNA adducts. The AA-DNA adducts are believed to be associated with the nephrotoxic and carcinogenic effects of AA. In this study, liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS) was used to identify and quantify the AA-DNA adducts isolated from the kidney and liver tissues of the AA-dosed rats. The deoxycytidine adduct of AA (dC-AA) and the deoxyadenosine-AA adduct (dA-AA) were detected and quantified in the tissues of rats with one single oral dose (5mg or 30mg AA/kg body weight). The deoxyguanosine adduct (dG-AA), however, was detected only in the kidney of rats that were dosed at 30mg AA/kg body weight for three consecutive days. The amount of AA-DNA adducts found in the rats correlated well with the dosage.

Causality assessment of herb-induced liver injury using multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM).

Objective. To evaluate an algorithmic approach involving a multidisciplinary team for causality assessment of suspected herb-induced liver injury (HILI) cases and to compare the causality score using this multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM). Methods. A team consisting of hepatologist, clinical toxicologist, analytical toxicologist, and Chinese medicine (CM) pharmacist was formed to do causality assessment based on a protocol for suspected HILI cases. The likelihood of the diagnosis of individual case was first assessed systematically by a hepatologist and clinical toxicologist independently after collecting information about four aspects: (1) clinical course, (2) exclusion of alternative causes, (3) quality of the prescription and herbal product by examining the CM prescriptions and analysis of biological and herb samples, (4) scientific support on comprehensive literature review on English and Chinese medical database, and subsequently concluded in a consensus meeting held by the multidisciplinary team. The final causality score of each patient was compared with the likelihood of causality as assessed by RUCAM. Results. Between 2005 and 2007, 48 consecutive patients with suspected HILI were enrolled and 21 patients were excluded due to the establishment of an alternative cause of liver impairment or the lack of any information on the herbs taken. Twenty-seven patients were recruited, among them 15 consumed Chinese herbal medicines, 10 used proprietary Chinese medicinal products, and 2 used both. The concordance between the causality assessment of the hepatologist and clinical toxicologist was moderate (weighted κ = 0.48, 95%CI 0.30–0.66). The causality assessment process concluded that the likelihood of HILI was “highly probable” in 5 cases and “probable” in 12, whereas there were 5 “highly probable” and 16 “probable” cases as assessed by RUCAM. The causality assessment by the multidisciplinary approach and RUCAM also showed moderate agreement (weighted κ = 0.51, 95%CI 0.22–0.81). Conclusion. A multidisciplinary approach using defined algorithms is a scientific approach in causality assessment for HILI. Further study is needed to assess its accuracy and applicability.

Factitious thyrotoxicosis and herbal dietary supplement for weight reduction

This article describes three patients who developed factitious thyrotoxicosis, as well as other adverse effects, after taking herbal dietary supplements for weight reduction. All products were found to contain undeclared animal thyroid tissue and western pharmaceuticals causing the adverse effects. Adulteration is concealed addition of undeclared drugs, or other substances with therapeutic effects, to a health product. Consumption of such products, and the concealed components unwittingly, is obviously dangerous. Multiple adulterants in one product are often seen. Untoward adverse effect or drug interaction could occur. Overdose subsequent to poor standardization of the adulterants is another concern. Health care professionals must therefore be aware of the potential dangers posed by adulterated dietary supplements.

Hepatitis induced by Teucrium viscidum

Introduction. In Hong Kong, Chinese medicine is popular and coexists with orthodox Western medicine. Despite a long history of use, many herbs have not been submitted to rigorous scientific testing and there are reports of hepatotoxicity. We describe a woman who developed acute hepatitis after drinking an herbal remedy containing Teucrium viscidum. Case report. A previously healthy 51-year-old woman was admitted to a regional hospital because of jaundice, with complaints of nausea, vomiting, and tea-colored urine for three days prior to admission. She denied any recent ingestion of known hepatotoxins, but she had consumed an herbal remedy for low back pain for three days before the onset of symptoms. She was icteric and had a serum total bilirubin level of 11.4 mg/dL, alanine aminotransferase of 2620 U/L, aspartate aminotransferase of 1876 U/L, and alkaline phosphatase level of 186 U/L. Discontinuation of the herbal remedy resulted in normalization of the liver enzymes two months later. Discussion. This is the first report of hepatitis probably related to use of Teucrium viscidum. The herb is infrequently used in Chinese medicine for treatment of rheumatic and bleeding disorders. T. viscidum contains teucvin, similar to other Teucrium species and is related to T. chamaedrys, commonly known as germander, which is a well documented cause of hepatotoxicity. Conclusions. Our findings suggest that Teucrium viscidum can cause hepatotoxicity similar to that of germander.