Paclitaxel (trade name Taxol) is derived from the bark of the Pacific yew tree (Taxus brevifolia) and is used to treat breast, lung, and ovarian cancer.
In Agatha Christie's book A Pocket Full of Rye, the first victim is murdered when his marmalade is spiked with poisonous yew berries.
What is popular lore on the poisonous or medicinal properties of the yew tree? Culpeper’s Complete Herbal & English Physician (1826) states “Many in this country have eaten yew berries and survived. The tree’s very powerful poisonous qualities rise by distillation.” He goes on to say that, despite these qualities, yew berries are “sometimes given usefully in obstructions of the liver and bilious complaints.” In The Complete Book of Herbs, Lesley Bremness notes that all parts of the English yew are poisonous, yet a homeopathic tincture made from the leaves and berries is used medicinally. In the homeopathic literature, the bark, branch tips, and needles of the yew are used to treat diphtheria, tapeworms, tonsillitis, liver conditions, and rheumatism.
HISTORY OF PACLITAXEL
In 1961, the National Cancer Institute (NCI) began screening thousands of plant compounds for their anticancer properties. Samples of Pacific yew were first collected in 1962 by researchers from the U.S. Department of Agriculture (USDA) who were under contract to help the NCI in their search for natural products that might cure cancer. And compounds derived from the bark of the Pacific yew tree (Taxus brevifolia) showed promise. Extracts from this bark proved cytotoxic, although even after identification of the extract's most active component, it still took several years to isolate paclitaxel in its pure form. Testing was undertaken to identify the biological action of the new compound.
It was not until 1977 that the NCI was able to confirm antitumor activity in a mouse melanoma model. Because of difficulties harvesting the drug and the complexity of synthesizing the compound, development toward the clinic was slow. The drug, however, showed effectiveness against mammary tumors and ovarian cancer, pushing researchers to find a means of isolating large quantities for clinical use. Clinical trials became possible when a method was derived to extract a precursor, 10-deacetyl-baccatin III, from the common yew. The precursor was then converted by chemical synthesis to paclitaxel. Today, a cell culture method is used to produce the drug.
MECHANISM OF ACTION
Paclitaxel is a novel agent that interferes with the normal function of microtubule growth; at high concentrations it induces mitotic arrest in the G2/M phase of cell growth, and at low concentrations it causes apoptosis in the G0 and G1/S phases. Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle. The drug binds to a cell's microtubule assembly and slows cell division and growth by stabilizing the microtubules, preventing shrinkage, and therefore blocking segregation of chromosomes.
It was difficult to formulate paclitaxel into a delivery system acceptable for human use. Initial activity was observed with bulk drug suspended in solution. Although paclitaxel was soluble in 75% polyethylene glycol, repeated testing using this formula produced inferior results. When the drug was formulated in an ethanol, Cremophor, and saline solution to a particular concentration, intraperitoneal activity was preserved at initial levels. Preclinical toxic effects were most evident in tissues with a high cell turnover, such as hematopoietic, lymphatic, gastrointestinal, and reproductive tissues.
In 1992 the FDA approved paclitaxel (Taxol) for the treatment for ovarian cancer. Clinical trials to test treatment in other types of cancers and in combination with other therapies resulted in indications for breast cancer, lung cancer, and Kaposi's sarcoma.
Frontiers in Pharmacology review article examines the safety of herbal medicines
EXPLOSIVE GROWTH OF HERBAL MEDICINES
Viewed as a balanced and moderate approach to healing, herbal medicines have grown exponentially. This popularity is attributed to a preference for natural therapies and a greater interest in alternative medicines. Traditional medicinal practice involving herbs is an integral part of many communities, and the World Health Organization (WHO) estimates that 80% of the world’s population relies on herbal medicine as a primary source of healthcare. Strategic marketing by manufacturers of herbal medicines has expanded product visibility, and the continuous introduction of new herbal products into the market has led to public health issues and safety concerns.
All medicines must be safe and of suitable quality, yet a single herb plant may contain hundreds of natural constituents. Such complexity means that the control of raw herbal materials and finished herbal products is more involved than for conventional pharmaceuticals. A substantial proportion of the global drug market, herbal medicines require pharmacovigilance and safety monitoring. The WHO recommends national quality specifications and standards related to the manufacturing, import, and marketing of herbal materials; however, in most countries, herbal medicines arrive on the market without mandatory safety or toxicological evaluations and without evidence of quality and efficacy. The common misconception that natural products are nontoxic and devoid of adverse effects leads to improper use and unrestrained intake, along with the risk of severe poisoning and acute health problems. Herbal medicinal products have been implicated in cases of poisoning, with certain compounds capable of reacting with cellular macromolecules including DNA and inducing cellular toxicity and/or genotoxicity.
SAFETY AND TOXICITY
The safety of traditional and herbal medicines is paramount to national health authorities and the general public, yet:
Possible causes of adverse events resulting from the consumption of herbal medicines include
mistaken use of the wrong plant species, misidentification of medicinal plants, adulteration of herbal products with undeclared medicines, mislabeling of herbal medicinal products, contamination with toxic or hazardous substances, overdose, and misuse of herbal medicines by healthcare providers or consumers – including concomitant administration with other medicines. Predictably, adverse event analysis with herbal medicines is more complex than with conventional pharmaceuticals.
Evaluation of product safety is further complicated by geographical origin of the plant material, processing technique, route of administration, and compatibility with other medicines.
PROPERTIES OF SPECIFIC HERBS
Aristolochic acids and Aristolochia species. After findings of potential nephrotoxicity and carcinogenicity of aristolochic acids, studies confirmed their genotoxic activity. Aristolochic acid-related DNA adducts have been found in the renal tissues of patients; these mutagenic adducts are usually poorly repaired and capable of persisting for years in DNA. All plants in the genus Aristolochia contain aristolochic acids and are banned in Europe and the United States. Intake of slimming pills containing the Chinese herb Aristolochia fangchi has been linked to Aristolochic acid nephropathy and the development of subacute interstitial fibrosis of the kidneys and urothelial malignancies.
The tubers and roots of the Aconitum species have been used medicinally for centuries in herbal preparations for stroke, heart failure, diabetes, rheumatic fever, painful joints, gastroenteritis, edema, bronchial asthma, and other disorders. Aconitum carmichaeli and Aconitum kusnezoffii are used traditionally for pain relief. The toxicity of these plants derives primarily from the presence of diester diterpene alkaloids. Severe cases of cardiotoxicity from consumption of aconitine-containing herbal preparations manifest as ventricular tachycardia and fibrillation and eventually death. Bradycardia and hypotension have also been observed. The toxicity of aconitine and related diterpene alkaloids can be denatured by special processing and in China only the processed (i.e., detoxified) tubers and roots of Aconitum can be administered orally. More than 70 techniques are applied to the processing of Aconitum roots in order to reduce levels of toxic alkaloids below a certain threshold; note that this principle is not accepted in Europe.
Traditionally, Tussilago farfara or coltsfoot has been used for thousands of years to treat pulmonary complaints, acute and chronic coughs, bronchitis, laryngitis, and asthma. The polysaccharides are anti-inflammatory and immuno-stimulating, as well as demulcent, and the flavonoids have anti-inflammatory and antispasmodic actions. Tussilago farfara is generally regarded as nontoxic, although total alkaloids isolated from this plant have demonstrated hepatotoxicity. Recently, the effects of the pyrrolizidine alkaloids found in Tussilago farfara were reviewed and hepatic veno-occlusive disease and cirrhosis suggested as potential disease outcomes in humans. Restricted intake of pyrrolizidine-containing herbs is recommended.
There are reports on the efficacy of Garlic (Allium sativum) for management of hypertension and hypercholesterolemia. The main compound in the fresh plant is alliin, which on crushing undergoes enzymatic hydrolysis by alliinase to produce allicin. Due to the antiplatelet effects of garlic, care should be taken if given in combination with antiplatelet drugs and warfarin. Adverse effects associated with garlic extract include burning sensation in the gastrointestinal tract, nausea, diaphoresis, and lightheadedness.
The active compounds of St. John’s wort (Hypericum perforatum) include hypericin, hyperforin, and melatonin. The plant has clinically well-established effects for mild depressive symptoms, although allergic reactions, headache, dizziness, restlessness, fatigue, gastrointestinal symptoms, and photosensitivity have been reported, as well as hyperesthesia and a syndrome of dyspnea and hyperventilation with mydriasis, nausea, palpitations, and tremors. Interaction of St. John’s wort with antidepressants and anticoagulants has been demonstrated and use is not recommended in pregnancy because of the herb’s uterotonic activity.
It is vital to inform and protect the public by identifying risks associated with herbal medicines, incorporating herbal products into pharmacovigilance systems, linking safety monitoring to the regulatory status of herbal medicines, promoting safe use through adequate labeling and appropriate patient information, advancing knowledge of traditional, complementary, alternative, and herbal medicines within national drug regulatory authorities, and standardizing definitions and categorizations of herbal medicinal plants on an international level. Herbal medicines must be assessed for safety, toxicity, efficacy, and quality.
Providers of medicines – physicians, nurses, and pharmacists – need training to understand how herbal medicines affect the health of their patients. Healthcare professionals and medical communicators (translators and writers) must inform the public. The right knowledge base is crucial.
Citation: Ekor M (2014) The growing use of herbal medicines: issues relating to
adverse reactions and challenges in monitoring safety. Front. Pharmacol. 4:177. doi:
Integrative Translations specializes in Chinese-to-English translation of conventional and complementary medicine.
Effectiveness of turmeric and tuina therapies
At minimum, awkward word choices and poorly written English distract the reader. In the worst-case scenario, poor English translations are incomprehensible and the goal of clear and accurate communication is not met.
Below are errors encountered in Chinese-to-English translations.
Errors in verb tense Verbs are not inflected, or conjugated, in Chinese. The translator must look for context clues, such as "previously" or "in the future," in order to select the correct verb tense for the English translation. Auxiliary verbs in the Chinese source text may pose challenges in English translation, for example, the past conditional tense, "I would have gone."
Errors in number The Chinese language does not differentiate singular and plural nouns. Again, context is key.
Improper use of articles There are no definite (the) or indefinite (a, an, some) articles in the Chinese language. Proper understanding of English rules for the use of definite and indefinite articles is vital to the production of accurate written English.
Awkward word order or syntax Chinese has many options for sentence construction:
subject + verb + object
descriptive phrase/relative clause + noun + verb
topic (subject or object) + comment (sentence or phrase)
A common error in rendering text from Chinese to English is to mirror the Chinese word order exactly, almost a one-to-one replacement.
Word choice English has one of the largest vocabularies of all the world's languages. Its influences include Greek, German, Latin, and French, and the borrowing continues to this day! With so many options and so many synonyms or near synonyms, the right word choice is not always obvious. In certain situations the Germanic word is preferred, and in other situations the Latinate word is preferred. Preposition choice is especially thorny. The preposition a writer chooses may reveal non-native facility with the English language.
Options for the translation of Chinese medical terms into English:
Note that the same Chinese character is used for different registers in English.
More questions about translation? Contact Integrative Translations.
JANUARY 24TH UPDATE FROM THE CHINESE GOVERNMENT WEBSITE
- systemic chills and body aches
- breathing difficulties
- loss of appetite
- chest pain
Novel coronavirus was confirmed through positive nucleic acid testing and monitored by electrocardiogram, lung CT, and blood-gas analysis. Therapies included oxygen, extracorporeal membrane oxygenation, endotracheal intubation (refused in some cases), anti-infectives, antibiotics, antipyretics, analgesics, and sedatives, supplemental fluids, and symptomatic therapies.
Outcomes were intensifying respiratory failure, continuous declines in terminal oxygen saturation, reduced blood pressure, and ultimately death.
Seven hospitals in Wuhan are offering intake for patients with high fever in order to identify new cases.
How to tell if a document is written in Chinese, Japanese, or Korean
Chinese, Japanese, and Korean all use characters, sometimes they use the same characters. While modern Japanese is a mix of kanji (Chinese characters) and the katakana and hiragana syllabaries, most of the time Korean is written in the Hangul alphabet, although I have seen older Korean documents written with Chinese characters.
Here are some clues to help you differentiate: Chinese characters are, in general, more complex. They look denser. A written Chinese character, whether traditional (Hong Kong, Taiwan) or simplified (China, Singapore), has more strokes than a Japanese or Korean character.
Look for "no" (の). Look for dots(び). The Japanese language uses Chinese characters (kanji) and it uses two syllabaries (kana) of characters with only a few strokes. A Japanese document will contain multiple occurrences of the character “no” (の) which means “of” or denotes possession. So, glance through the document, do you see の scattered throughout? Then, it’s Japanese. Double dots also appear frequently, e.g., グ and ガ and ド.
I look for ovals. The Korean language has its own phonetic writing system, sometimes described as an alphabetic syllabary, and an oval shape appears frequently, for example, 여 and 우 and 으 and 어. You won’t see these oval shapes in Chinese. When you see a oval or circle shape in the Japanese language, it is a small circle パ.
敏捷的棕色狐狸跳過了懶狗 (traditional Chinese)
敏捷的棕色狐狸跳过了懒狗 (simplified Chinese)
빠른 갈색 여우는 게으른 개를 뛰어 넘는다 (Korean)
cáo nâu nhanh (Vietnamese)
хурдан бор үнэг (Mongolian)
быстрая коричневая лиса (Russian)
γρήγορη καστανή αλεπού (Greek)
الثعلب البني السريع (Arabic)
שועל חום מהיר (Hebrew)
ፈጣን ቡናማ ቀበሮ (Amharic)
Write me at https://www.integrativetranslations.com/contact.html. I will look at your document and let you know.
Kerilyn Sappington is the founder of Integrative Translations, which specializes in the Chinese to English translation of topics in conventional and complementary medicine.
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