巴拉圭中毒 / Alpha-Lipoic acid

[chenyh12345]

偶剛剛找期刊發現...
巴拉圭中毒也有人用ㄟ...

附上這一篇期刊以資證明...

Paraquat-induced oxidative stress in drosophila melanogaster-effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid.pdf

問個外行的問題

巴拉圭中毒

致病mechanism？

死亡率多少？

解毒藥？

台灣有無用 Alpha-Lipoic acid ( 硫辛酸 ) 治療的經驗？

[chen5252]

以前老師說
必死!!!!!!
沒遇到活的

[TSGHCGH]

巴拉圭中毒 死亡率超過 80 %, 致死的機轉 ( Mechanisms ): Multiple organs failure, esp. Acute renal failure( ARF), Liver failure & Respiratory failure caused by pulmonary fibrosis. Most cases died within 2 weeks. 還要看 中毒 的劑量是多少 ? 以及送醫處理的時間延誤多少 ? （阿飄） （阿飄）

[blind faith]

附上這一篇期刊以資證明...

Paraquat-induced oxidative stress in [color=#FF0000]drosophila melanogaster[/color]-effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid.pdf

Drosophila melanogaster -> "果蠅" !?

MK 大, 您愛說笑了. "人蟲殊途" 啊......你敢試啊?

[genome]

Drosophila melanogaster -> "果蠅" !?

沒錯!!

[MK]

附上這一篇期刊以資證明...

Paraquat-induced oxidative stress in [color=#FF0000]drosophila melanogaster[/color]-effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid.pdf

Drosophila melanogaster -> "果蠅" !?

MK 大, 您愛說笑了. "人蟲殊途" 啊......你敢試啊?

PO了這麼久...
終於有人發現了...

[kcjeson]

巴拉圭中毒 死亡率超過 80 %, 致死的機轉 ( Mechanisms ): Multiple organs failure, esp. Acute renal failure( ARF), Liver failure & Respiratory failure caused by pulmonary fibrosis. Most cases died within 2 weeks. 還要看 中毒 的劑量是多少 ? 以及送醫處理的時間延誤多少 ? （阿飄） （阿飄）

給氧只會加速死亡
最痛苦的死法
綠色農藥要小心

[chenyh12345]

巴拉圭中毒 死亡率超過 80 %, 致死的機轉 ( Mechanisms ): Multiple organs failure, esp. Acute renal failure( ARF), Liver failure & Respiratory failure caused by pulmonary fibrosis. Most cases died within 2 weeks. 還要看 中毒 的劑量是多少 ? 以及送醫處理的時間延誤多少 ? （阿飄） （阿飄）

問題是

什麼mechanism

造成

Multiple organs failure, esp. Acute renal failure( ARF), Liver failure &

Respiratory failure caused by pulmonary fibrosis

是否與某些減肥藥造成的pulmonary fibrosis有關﹖

[chenyh12345]

給氧只會加速死亡
最痛苦的死法
綠色農藥要小心

why﹖

[blind faith]

MK, 去找原文啦....

Crit Rev Toxicol 2008;38(1):13-71

Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment.

Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.

[blind faith]

給氧只會加速死亡

跟 paraquat intoxication mechanism: Redox cycling 有關,會產生superoxide radical...

找到一篇 1974 的 review:

paraquat.pdf

(789.96 KiB) 已下載 393 次

[kcjeson]

我不記得了
只記得 care這類病人不可給氧
想要進一步了解
可電榮總毒物科
他們有豐富的資料可拿
巴拉圭這議題應該有他們毒物科的journal可拿
當然最後快failure時
還是人道性的給氧
接到這種病人不要急著救病人
切記先避免被殘餘農藥汙染自己

[chenyh12345]

第一次看到 " 硫辛酸 " 這個名詞
是在一片SARS恐慌的時機

桃園中壢
一位熱心的
小兒科彭奕奇醫師
在報紙上發表
" 何不試試硫辛酸﹖---超級抗氧化劑，可強力抑制發炎 "

由於天天接觸的都是URI病人
心想
如果得到SARS，只能聽天由命
不如
找一些另類療法

在書局找到一本
抗氧化劑硫辛酸的奇蹟
Burt Berkson MD PHD 著 / 郭素菁譯
世茂出版社

其中提到
誤食野菇Amanita verna
GOT GPT高達數千
一般都會死於hepatic failure
用了硫辛酸後
安然無恙

巴拉圭中毒
是否也可試試﹖

[albarto1688]

YOU CAN BUY ANY 農藥 IN TAIWAN EASILY
IF YOU WANT TO... （阿飄） （無盡漩渦）

[willcheng77]

巴拉圭中毒通常只要一點點的量就會掛
以前看過只喝兩口就掛了
非常恐怖的死法 全身的體液都是綠色
好像沒什麼好方法
我看過的沒有一個活著

[chenyh12345]

巴拉圭中毒通常只要一點點的量就會掛
以前看過只喝兩口就掛了
非常恐怖的死法 全身的體液都是綠色
好像沒什麼好方法
我看過的沒有一個活著

為什麼

只要一點點的量就會掛

跟dose不相關﹖

[genome]

為什麼
只要一點點的量就會掛
跟dose不相關﹖

Paraquat IC50只有幾十uM
多喝一點 可能也沒多幾條命可以多死幾次哦
(冷吱吱) (吐血) (裝死)

[歌劇迷]

請問這種除草劑的俗名叫什麼？看起來真的很恐怖.........如果有人隨便拿來濫用怎麼辦？

[blind faith]

歌大:

Paraquat (巴拉刈)

特性：
　　巴拉刈是一種快速作業的接觸性殺草劑，對人類而言屬於一種劇毒性農藥。絕大多數的中毒患者多因一時不慎，造成無法挽救的悲劇。極少量未稀釋巴拉刈溶液(約10c.c.)即可造成不可復原性傷害。因而認識巴拉刈的特性，進而強調並保持高度的警覺性，以免造成無法挽救的傷害，是每一位接觸到此類農藥者應注意防範的。
　　巴拉刈除了當用作殺草劑，亦可作為乾燥促進劑、魚類黏液菌病害控制用。市面上常以巴拉刈的二氯鹽台硫酸鹽型態出現，屬水溶性。它很容易在土壤中分解，正確地使用時不易對操作者的健康、野生動物或環境，產生不良影響。對誤用或服食者則對各組織造成迅速且不可恢復的傷害。

種類：
　　多以24%濃度形態出售，顏色呈藍綠色及深咖啡色兩種，市面可見的產品如下24%速草淨（正豐）、綜免刈（功力）、全草滅（日農）、草蕪松（興農）、巴拉刈、克蕪蹤（ICI GRAMOXONE & WEEDOL）、可樂松及42%巴達刈（保達克混合水劑）。


請參考

http://en.wikipedia.org/wiki/Paraquat

http://www.syngenta.com.tw/htm/safe/07.asp

http://itap.sinon.com.tw/poison/main2-1.htm

[blind faith]

Paraquat IC50只有幾十uM
多喝一點 可能也沒多幾條命可以多死幾次哦
-------------------------------------------------

◎毒性：劇毒性農藥 LD50 < 50mg / kg 動物實驗

暫不論老鼠與人的差異
以成人體重 60-70kg 來算, 只要 <3-3.5 克就會掛了 （阿飄）

[blind faith]

林口長庚林杰樑教授的藥物治療方式:

Crit Care Med. 2006 Feb;34(2):368-73

Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning.

OBJECTIVE:
Paraquat is widely used in the world, and all treatments for paraquat poisoning have been unsuccessful. Many patients have died of paraquat poisoning in developing countries. A novel anti-inflammation method was developed to treat severe paraquat-poisoned patients with >50% to <90% predictive mortality: initial pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 2 days), followed by dexamethasone 20 mg/day until Pao2 was >11.5 kPa (80 mm Hg) and repeated pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 1 day), which was repeated if Pao2 was <8.64 kPa (60 mm Hg).

DESIGN: Randomized controlled trial.
SETTING: Academic medical center in Taiwan.

PATIENTS:
Twenty-three paraquat-poisoned patients with >50% and <90% predictive mortality assessed by plasma paraquat levels were prospectively and randomly assigned to the control and study groups at a proportion of 1:2.

INTERVENTIONS:
The control group received conventional therapy and the study group received the novel repeated pulse treatment with long-term steroid therapy.

MEASUREMENTS AND MAIN RESULTS:
We measured patient mortality during the study period. There was not a different distribution of basal variables between the two study groups. The mortality rate (85.7%, six of seven) of the control group was higher than that of the study group (31.3%, five of 16; p = .0272).

CONCLUSIONS:
The novel anti-inflammatory therapy reduces the mortality rate for patients with severe paraquat poisoning.

[chenyh12345]

為什麼
只要一點點的量就會掛
跟dose不相關﹖

Paraquat IC50只有幾十uM
多喝一點 可能也沒多幾條命可以多死幾次哦
(冷吱吱) (吐血) (裝死)

數年前
discovery有一部片子介紹
某一種有機汞中毒

有個年輕的女化學家
實驗操作時
手套破掉
手指的表皮沾到 "一點點" 有機汞

一兩個星期就掛了

巴拉圭中毒
毒菇中毒
減肥藥造成的 pulmonary fifrosis
有機汞中毒
‧‧‧
這些中毒型式
mechanism好像有共通性

原理？
板凳中 (咦)

[blind faith]

有機汞 (organic mercury) 中毒, 應該是 neurotoxicity....

有幾種機制曾被提出來解釋汞如何毒殺神經細胞：

1.抑制蛋白質

2.阻斷粒線體的功能

3.直接影響神經的離子交換

4.阻斷神經傳導

5.破壞神經細胞群原有的網絡架構

see this link: http://www.dls.ym.edu.tw/neuroscience/merc_c.html

[blind faith]

FASEB J. 1994 Jun;8(9):622-9.

Mechanisms of methylmercury-induced neurotoxicity.

Mercury in both organic and inorganic forms is neurotoxic. Methylmercury (MeHg) is a commonly encountered form of mercury in the environment. Early electrophysiological experiments revealed that MeHg potently affects the release of neurotransmitter from presynaptic nerve terminals.
Recently, the hypothesis that these alterations may be mediated by changes in the intracellular concentration of Ca2+ ([Ca2+]i) has been supported. MeHg alters [Ca2+]i by at least two mechanisms. First, it disrupts regulation of Ca2+ from an intracellular Ca2+ pool and second, it increases the permeability of the plasma membrane to Ca2+. MeHg also blocks plasma membrane voltage-dependent Ca2+ and Na+ channels in addition to activating a nonspecific transmembrane cation conductance. Chronic MeHg exposure results in ultrastructural changes and accumulation of MeHg within mitochondria. In vitro, MeHg inhibits several mitochondrial enzymes and depolarizes the mitochondria membrane subsequently reducing ATP production and Ca2+ buffering capacity. Inhibition of protein synthesis is observed after in vivo or in vitro exposures of MeHg and may be an early effect of MeHg. Thus, the early cellular effects of exposure to MeHg are diverse and cell damage likely occurs by more than one mechanism, the effects of which may be additive or synergistic.

methylmercury.pdf

(1.95 MiB) 已下載 371 次

[chenyh12345]

FASEB J. 1994 Jun;8(9):622-9.

Mechanisms of methylmercury-induced neurotoxicity.

Mercury in both organic and inorganic forms is neurotoxic. Methylmercury (MeHg) is a commonly encountered form of mercury in the environment. Early electrophysiological experiments revealed that MeHg potently affects the release of neurotransmitter from presynaptic nerve terminals.
Recently, the hypothesis that these alterations may be mediated by changes in the intracellular concentration of Ca2+ ([Ca2+]i) has been supported. MeHg alters [Ca2+]i by at least two mechanisms. First, it disrupts regulation of Ca2+ from an intracellular Ca2+ pool and second, it increases the permeability of the plasma membrane to Ca2+. MeHg also blocks plasma membrane voltage-dependent Ca2+ and Na+ channels in addition to activating a nonspecific transmembrane cation conductance. Chronic MeHg exposure results in ultrastructural changes and accumulation of MeHg within mitochondria. In vitro, MeHg inhibits several mitochondrial enzymes and depolarizes the mitochondria membrane subsequently reducing ATP production and Ca2+ buffering capacity. Inhibition of protein synthesis is observed after in vivo or in vitro exposures of MeHg and may be an early effect of MeHg. Thus, the early cellular effects of exposure to MeHg are diverse and cell damage likely occurs by more than one mechanism, the effects of which may be additive or synergistic.

methylmercury.pdf

實驗操作時
手套破掉
手指的表皮沾到 "一點點" 有機汞

一兩個星期就掛了

mechanism好像與其他一般汞中毒不太一樣

[歌劇迷]

歌大:

Paraquat (巴拉刈)

特性：
　　巴拉刈是一種快速作業的接觸性殺草劑，對人類而言屬於一種劇毒性農藥。絕大多數的中毒患者多因一時不慎，造成無法挽救的悲劇。極少量未稀釋巴拉刈溶液(約10c.c.)即可造成不可復原性傷害。因而認識巴拉刈的特性，進而強調並保持高度的警覺性，以免造成無法挽救的傷害，是每一位接觸到此類農藥者應注意防範的。
　　巴拉刈除了當用作殺草劑，亦可作為乾燥促進劑、魚類黏液菌病害控制用。市面上常以巴拉刈的二氯鹽台硫酸鹽型態出現，屬水溶性。它很容易在土壤中分解，正確地使用時不易對操作者的健康、野生動物或環境，產生不良影響。對誤用或服食者則對各組織造成迅速且不可恢復的傷害。

種類：
　　多以24%濃度形態出售，顏色呈藍綠色及深咖啡色兩種，市面可見的產品如下24%速草淨（正豐）、綜免刈（功力）、全草滅（日農）、草蕪松（興農）、巴拉刈、克蕪蹤（ICI GRAMOXONE & WEEDOL）、可樂松及42%巴達刈（保達克混合水劑）。


請參考

http://en.wikipedia.org/wiki/Paraquat

http://www.syngenta.com.tw/htm/safe/07.asp

http://itap.sinon.com.tw/poison/main2-1.htm

謝謝blind faith大大的解說。

看了各位大大的發言，覺得很多人真的很辛苦：農夫，化學家，以及也會經常碰到藥物危險的醫師。我這個怕死又膽小的人，真的無法想像：如果自己的工作必須碰觸這類可怕的東東，會不會因此變成很不快樂....... (冷吱吱)

[blind faith]

實驗操作時
手套破掉
手指的表皮沾到 "一點點" 有機汞
一兩個星期就掛了
mechanism好像與其他一般汞中毒不太一樣
-----------------------------------------------------
organic mercury 致病的 mechanism 應該還是 neurotoxicity.

http://www.sailhome.org/Concerns/BodyBu ... rcury.html

In another example , a professor doing lab research was accidentally exposed to a some drops of dimethylmercury on the back of her gloved hand. This organic mercury diffused into the glove and then got absorbed by the woman.
After 3 months she began experiencing episodes of nausea, diarrhea, and abdominal discomfort. During the next 2 months she also began losing weight. At the end of 5 months she began to lose speech, balance, and the ability to walk. In the following days the woman noted "tingling in her fingers, brief flashes of light in both eyes, a soft background noise in both ears, and progressive difficulty with speech, walking, hearing, and vision (constricted visual fields)".
Her blood mercury level was tested and found to be 500x to 4000x higher than expected. Oral chelation was started, but neurodegeneration continued. Blood exchange transfusion didn't work because too much mercury was already in her body tissue.
By 6 months after exposure the woman became unresponsive to all visual, verbal, and light-touch stimuli. She had "periods of spontaneous eye opening, but without awareness". She exhibited spontaneous "yawning, moaning, and limb movements", with "periods of agitation and crying". The woman fell into a coma. Almost 10 months after exposure the woman was removed from life-support (per her advanced directives) and died.

This is a brief report about this researcher in NEJM(1998) :

http://content.nejm.org/cgi/content/full/338/23/1672

[blind faith]

http://en.wikipedia.org/wiki/Mercury_poisoning

Mercury poisoning's effects partially depend on whether it has been caused by exposure to elemental mercury, inorganic mercury compounds (as salts), or organomercury compounds.

Elemental mercury

Quicksilver (liquid metallic mercury) is poorly absorbed by ingestion and skin contact. It is hazardous due to its potential to release mercury vapour. Animal data indicate that less than 0.01% of ingested mercury is absorbed through the intact gastrointestinal tract; though it may not be true for individuals suffering from ileus. Cases of systemic toxicity from accidental swallowing are rare, and attempted suicide via intravenous injection does not appear to result in systemic toxicity. Though not studied quantitatively, the physical properties of liquid elemental mercury limit its absorption through intact skin and in light of its very low absorption rate from the gastrointestinal tract, skin absorption would not be high. Some mercury vapour is absorbed dermally but uptake by this route is only approximately 1% of that by inhalation.

In humans, approximately 80% of inhaled mercury vapour is absorbed via the respiratory tract where it enters the circulatory system and is distributed throughout the body. Chronic exposure by inhalation, even at low concentrations in the range 0.7–42 μg/m3, has been shown in case control studies to cause effects such as tremors, impaired cognitive skills, and sleep disturbance in workers.

Inorganic mercury compounds

Mercury occurs inorganically as salts such as mercury(II) chloride. Mercury salts primarily affect the gastro-intestinal tract and the kidneys, and can cause severe kidney damage; however, as they can not cross the blood-brain barrier easily, mercury salts inflict little neurological damage without continuous or heavy exposure. As two oxidation states of mercury form salts (Hg+ and Hg2+), mercury salts occur in both mercury(I) (or mercurous) and mercury(II) (mercuric) forms. Mercury(II) salts are usually more toxic than their mercury(I) counterparts because their solubility in water is greater; thus, they are more readily absorbed from the gastrointestinal tract.

Organic mercury compounds

Compounds of mercury tend to be much more toxic than the element itself, and organic compounds of mercury are often extremely toxic and have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethylmercury, is so toxic that even a few microliters spilled on the skin, or even a latex glove, can cause death.

Methylmercury is the major source of organic mercury for all individuals. It works its way up the food chain through bioaccumulation in the environment, reaching high concentrations among populations of some species. Larger species of fish, such as tuna or swordfish, are usually of greater concern than smaller species. The U.S. Food and Drug Administration (FDA) and the U.S. Environmental Protection Agency (EPA) advise women of child-bearing age, nursing mothers, and young children to completely avoid swordfish, shark, king mackerel and tilefish (golden bass), to limit consumption of albacore ("white") tuna to no more than 6 oz (170 g) per week, and of all other fish and shellfish to no more than 12 oz (340 g) per week. A 2006 review of the risks and benefits of fish consumption found that for adults the benefits of one to two servings of fish per week outweigh the risks, even (except for a few fish species) for women of childbearing age, and that avoidance of fish consumption could result in significant excess coronary heart disease deaths and suboptimal neural development in children.

Ethylmercury is a breakdown product of the antibacteriological agent ethylmercurithiosalicylate, which has been used as a topical antiseptic and a vaccine preservative (further discussed under Thiomersal below). Its characteristics have not been studied as extensively as methylmercury. It is cleared from the blood much more rapidly, with a half-life of 7 to 10 days, and it is metabolized much more quickly than methylmercury. It probably does not have methylmercury's ability to cross the blood-brain barrier via a transporter, but instead relies on simple diffusion to enter the brain.

Other exposure sources of organic mercury include phenylmercuric acetate and phenylmercuric nitrate. These were used in indoor latex paints for their anti-mildew properties, but were removed in 1990 because of cases of toxicity.

[chenyh12345]

實驗操作時
手套破掉
手指的表皮沾到 "一點點" 有機汞
一兩個星期就掛了
mechanism好像與其他一般汞中毒不太一樣
-----------------------------------------------------
organic mercury 致病的 mechanism 應該還是 neurotoxicity.

http://www.sailhome.org/Concerns/BodyBu ... rcury.html

In another example , a professor doing lab research was accidentally exposed to a some drops of dimethylmercury on the back of her gloved hand. This organic mercury diffused into the glove and then got absorbed by the woman.
After 3 months she began experiencing episodes of nausea, diarrhea, and abdominal discomfort. During the next 2 months she also began losing weight. At the end of 5 months she began to lose speech, balance, and the ability to walk. In the following days the woman noted "tingling in her fingers, brief flashes of light in both eyes, a soft background noise in both ears, and progressive difficulty with speech, walking, hearing, and vision (constricted visual fields)".
Her blood mercury level was tested and found to be 500x to 4000x higher than expected. Oral chelation was started, but neurodegeneration continued. Blood exchange transfusion didn't work because too much mercury was already in her body tissue.
By 6 months after exposure the woman became unresponsive to all visual, verbal, and light-touch stimuli. She had "periods of spontaneous eye opening, but without awareness". She exhibited spontaneous "yawning, moaning, and limb movements", with "periods of agitation and crying". The woman fell into a coma. Almost 10 months after exposure the woman was removed from life-support (per her advanced directives) and died.

This is a brief report about this researcher in NEJM(1998) :

http://content.nejm.org/cgi/content/full/338/23/1672

這個case很可能就是discovery所提到的

可怕的是
nearly hopeless & progressive clinical course



http://content.nejm.org/cgi/content/full/338/23/1672
文內提到
rapid conversion of dimethylmercury to methylmercury

而
dimethylmercury 的毒性比 methylmercury大得多

mechanism有沒有可能是 : (咦)
在生物體內dimethylmercury 轉變為 methylmercury 的過程中
產生了某種強力又不易被破壞的自由基
在這個強力又不易被破壞的自由基未被去活化前或未被被排出生物體前
一直在體內產生一個接一個的分子破壞﹖

有點類似
沒有人可制止的連續殺人犯
流竄在社會中