Talk:Neurotoxin/GA1

GA Review

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Reviewer: Pyrotec (talk · contribs) 22:56, 3 December 2012 (UTC)

I will review. Pyrotec (talk) 22:56, 3 December 2012 (UTC)

Initial comments

I've now done an initial quick read of the article and on balance it appears to be at or about GA-level, so "quick failing" this nomination is not appropriate and I will now review it against WP:WIAGA.

The article appears to be well referenced (I say "appears" because I've not checked them), comprehensive and well illustrated; however, the Lede (or WP:Lead) is a bit (well more than a bit) "indigestible", but I'll comeback to that later. I also see difficulties in determining the scope of the article from the lead, and that will make it difficult to assess the article against WP:WIAGA, clauses 3(a) & (b) although I suspect that the latter is OK. Pyrotec (talk) 20:40, 13 December 2012 (UTC)

(Done) There is also a {{citation needed}} flag present in the Background section which seems to date back to January 2012, some nine or ten month before this article was nominated at WP:GAN.

(Done) Also, a {{clarification needed}} flag in the Inhibitors subsection going back to February 2102

(Done) as well as a {{citation needed}} going back to April 2012. I did not spot these two flags earlier, or I might have invoked a "quick fail". Pyrotec (talk) 22:24, 7 December 2012 (UTC)

I'm now going to work my way through the article, starting at the Background section and finishing with the Lead, and highlight any "problems" that I find. This is likely to take a few days. Pyrotec (talk) 22:02, 7 December 2012 (UTC)

• Background -

• (Done) The first paragraph has a {{citation needed}} flag. I assume from its precise location it is asked for confirmation that lead acetate, (is) known as "sugar of lead"'; however, it could be referring to all the text that follows ref 21. I have a ref to hand (if needed) "for lead acetate, (is) known as "sugar of lead"". I also read a long time ago that wine was store in ceramic vessels that had a lead glaze, it's not in the article, but it could be another plausible(?) reason/explanation; but this is not a request/suggestion that lead glaze needs to be added.
• The final claim in this first paragraph: In part, neurotoxins have been part of human history because of the fragile and susceptible nature of the nervous system, making it highly prone to disruption., is unreferenced; and needs one.
• The second paragraph is quite readable, but its all based on ref 22, using Dobbs' book of 2009. Since its a book, a page number or page numbers should be provided in the citation (see Wikipedia:Citing sources and Wikipedia:Scientific citation guidelines).
• Similar comments apply to paragraphs three, four and five, refs 23 , 24 & 25 , in respect of "Widmaier 2008", "Martini 2009" and "Costa 2011".

• Applications in neuroscience -

...stopping at this point. To be continued. Pyrotec (talk) 23:01, 7 December 2012 (UTC)

• This whole section is referenced by a single citation, "Adams 2003", used three times. There is however no "Adams 2003" reference, but there is an "Adams, et al 1994 reference".
• It is quite a readable and informative section, but it is structured as a single paragraph:

• The first part has an introductionary function, moves on to "attack by both predators and prey" and then discusses venon. This is not Applications in neuroscience, but I'll accept it as an introduction.
• The rest is about targetting by radiolabelled species, measurement and "understanding", so could this be moved into a separate paragraph. and is it Applications in neuroscience? It looks like research to me, so is the section title accurate or should it be renamed to something more description of what appears in the section? Pyrotec (talk) 16:06, 9 December 2012 (UTC)

• Mechanisms of activity -

• In general I found this to be a relatively easy section to read. My main concern is that many of the references are books and they are just called as (for example) Smith 2003; in contrast when journals are used, and there are a lot, they are properly cited and verifiable because page numbers are given in the references.
• This section starts off with a table of two columns, labelled "Neurotoxin classification" and "Neurotoxins", respectively, but it is not made clear whether the items that appear in the "Neurotoxins" column are (typical or sole?) examples showing a certain type of property, e.g. inhibition of some channel, barrier, or release, or whether they the only known material that has that property. For example almost half of lines have two neurotoxins list and almost half have one example listed, but none have more that three examples and no example appears on more than once so they appear to have only one mode/channel of "inhibition".
• I'm not sure what "it" is referring to in the second paragraph of Tetrodotoxin. I assume that "it" is TTX and that is the logical deduction. The problem is that the previous sentence is about TTX-r, but the rest of the paragraph is about TTX, so could "it" be TTX-r? Alternatively, there is a bit in the first paragraph on TTX-s, so should the TTX-r material be moved to the first paragraph?
• There is a {{clarification needed}} flag going back to February 2012 in sodium channel Inhibitors.

At this point, I can see the end of the article and it just seems to stop. So I'm opening a new subsection on Scope & what is this article about?.

I would expect to be continuing this section after the conclusion of the following subsection. Pyrotec (talk) 15:02, 9 December 2012 (UTC)

Scope & what is this article about?

I normally do the WP:Lead last.

The lead has two main functions (see WP:Lead): (1) to introduce the topic of this article and (2) to summarise the main points in the article. It also has some constraints, for instance the Lead should not "tease" by discussions topics/subjects that don't appear in the body of the article and the "relative balance" of the lead should be similar to that of the body of the article. For these reasons, I find it easier to review the body of the article to find out what it is about and then go and review the Lead to see if it is "compliant".

Having got through the article to Mechanisms of activity/Inhibitors I think I need to step back and find out what this article is about. As I'll need to do this inorder to assess the article against WP:WIAGA, clauses 3(a) & (b) although I suspect that the latter is OK. Pyrotec (talk) 20:40, 13 December 2012 (UTC)

I think this is what the article is about. If I've got it wrong, please say so.

• Background -

• An interesting section. The Romans got lead poisoning 2500 to 2000 years ago; nervous tissue is complex and can get disrupted by disturbances in its environment; there are barriers such as BBB; consideration of hydrophobic and hydrophilic; EPA testing; in-vitro & in-vivo testing; screening.
• Looks Good.

• Applications in neuroscience -

• Is this the correct title? The title does illustrate what i was trying to communicate here, being how these neurotoxins have become very useful in the scientific study of the nervous system, and only provide examples of the predators and prey to illustrate evolutionarily why these compounds developed in the way they did and why they can be used in the way that they are.
• Discussion of targetting by predators and prey; Venom; measurements using radio-labelled TTX; Hodgkin–Huxley model; understanding of some common compounds.

• Mechanisms of activity -
  • Inhibitors -

• Discussion ordered by channel, release or barrier.
• A table of toxins. Some come from animals/fish and some are chemicals (inorganic or organic). A few are eaten as food or used as "treatments". A few are used as "weapons of war". Lethal dose and time to incapacitate/kill varies from very quick to many years.
• For the table, the "bad effects" are described for most/all of them. Very few have any discussion of antidote or cures.

• • Receptor agonists and antagonists -

• Organic origin; kills

• • Cytoskeleton interference -

• Inorganic origin; industrial/environmental chemical.

• • Calcium-mediated cytotoxicity -

• Lead (Pb).

• • Neurotoxins with multiple effects & n-Hexane -

• Liquid chemical solvent(s).

• • Endogenous neurotoxin sources -

• "Things" (chemicals) inside the body.

• Lead (Lede) -

• First paragraph: Greek, Latin word meaning poison; adversely affects nervous tissue; label for toxic compounds; ability to target useful for studying nervous systems; list of examples.
• Second paragraph: characterised by inhibition or communication; pathology; treatments.

My first impression is that the scope of the lead is broadly compatible with that of the body of the article with one exception. The Lead states: Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant,[9] antitoxin[19] and ethanol[20] administration. I think that this may be out of balance with the body of the article:

• Tetrodotoxin has a discussion of treatment: The use of the acetylcholinesterase inhibitor Neostigmine or the acetylcholine antagonist Atropine, however, can increase sympathetic nerve activity enough to improve the chance of survival after TTX exposure

...Stopping for now. To be continued. Pyrotec (talk) 23:09, 8 December 2012 (UTC)

• Botulinum toxin has a discussion of treatment:It has been shown that capsaicin (active compound responsible for heat in chili peppers) can bind the TRPV1 receptor expressed on cholinergic neurons and inhibit the toxic effects of BTX.[19].
• Arsenic has a discussion of treatment: Additionally, similar to other neurotoxin treatments, the administration of certain antioxidants has shown some promise in reducing neurotoxicity of ingested arsenic.[87].
• Ammonia has a discussion of treatment: Administration of antioxidants or glutaminase inhibitor can reduce this mitochondrial transition, and potentially also astrocyte remodling.[92]
• Tetraethylammonium, Chlorotoxin, Curare, Conotoxin, Tetanus toxin, Aluminum, Mercury, Anatoxin-a, Lead, Ethanol, n-Hexane and Endogenous neurotoxin sources have no discussion of treatments.

I think this article is about Neurotoxins and in particular their use in the study of nervous systems thought their ability to specifically target neural components. There are quite a few examples of Neurotoxins and how they might interact with the body and some information on treatment(s). This includes some information on the problems associated with the use of lead, to show the antiquity" of the topic of neurotoxin/Neurotoxicity.

• Its not an environmental/occupational health topic, e.g. these chemicals are dangerous for these reasons (which is covered); this is how to protect yourself from harm; and this is the treatment.
• It briefly mentions war-like uses of these materials, but it not about these.
• It doesn't seem to be an accident and emergency guide to identification and treatment.

Pyrotec (talk) 16:03, 9 December 2012 (UTC)

Initial comments (continued)

• Mechanisms of activity (continued) -
  • Synaptic vesicle release -

• Compliant.

• • Blood brain barrier -
    • Aluminum -

• A good section. Is there any information from academic studies / inquests arising from the Camelford water pollution incident, I half-remember mention on the TV of Alzheimer’s-Disease-type "problems" and inquests mentioning visible brain damage of the type shown by Alzheimer’s suffers?

• • • Mercury -

• A good sub-sub-section and well referenced. I would ask whether exposure to mercury vapour as a result of occupation/work needs a mention? There is/was a phrase "as mad as a hatter" and that seems to have been as a result of chronic mercury poisoning from the use of acidic mercury nitrate to treat felt made from animal skins. There were other occupational uses for mercury/salts/amalgams, but this one seems to have been notable.

• • Receptor agonists and antagonists -

• Looks to be compliant.

• • Cytoskeleton interference -
    • Arsenic -

• A good sub-sub-section and well referenced. Chemistry World recently (possibly this one in September) had an interesting article on groundwater pollution, by arsenic, in places such as Bangladesh and India where arsenic is brought to the surface by a combination of land irrigation and water extraction from the ground.
• Arsenic was also used as a pigment for wallpapers by William Morris and the Arts and Crafts movement and as an insecticide. Mostly, if not entirely banned now.

• • • Ammonia -

• Looks to be compliant.

• • Calcium-mediated cytotoxicity -
    • Lead -

• Mention is made that Lead's toxicity has been recognized for at least thousands of years.[93], but no mention is made here of how exposure arises. There is an adjacent image of a lead water pipe with the title "Lead pipes are common sources of ingested lead" and the topic was discussed earlier in the Background section.

...stopping for now. To be continued. Pyrotec (talk) 21:07, 20 December 2012 (UTC)

• I would, however, question whether the statement that Lead's toxicity has been recognized for at least thousands of years is right. The installation of lead piping in water supplies in houses continued way past WW II and it does not seem to have be been banned or if it has, its only been done very recently (perhaps last 20-25 years). Its not been used for "new builds" for perhaps that length of time; but I don't think there is any compulsion to remove it from existing homes, as far as the UK is concerned. It, the dissolving by water of lead from the pipe walls, is a problem that is mainly confined to "soft water" areas. Banning of the use of lead-based solders on domestic water pipes is something else that has happened only in the last decade or so.
• A summarised overview of potential exposures could be provided to update the 2000 year old "sugar of lead" problem discussed in the Background section. Lead paints were formerly used, so lead-based paints may still be found in older homes, albeit overpainted by oil-based and now water-based paints. Lead pipes and solder joints, made with lead-based solders, are still in use in cold-water supplies in many homes. Tetraethyl lead was used for the best part of 90 to 100 years as an additive for petrol (gasoline for the US). It was incompatible with platinum-based catalytic converters and that caused the change over to lead-free petrols. I vaguely remember the results obtained from a study of lead levels being monitored in the playgrounds of primary schools along A roads, with many of the lead levels in Birmingham's schools being at or over the workplace exposure limits (presumably the eight-hour limit). Its not my field, but lead has other toxicity effects beyond neurotoxicity I suspect that lead poisoning of children is more significant than poisoning older people.

• • Neurotoxins with multiple effects -
    • Ethanol -

• To me a good section and compliant.
• I suspect that the results shown are those caused by "pure" alcohol, by that I mean alcohol (and mixtures of alcohol and water) in the form of beverages that can be purchased legally for consumption, such as whisky, beer, etc. Consuming alcohol that has been legally "denatured" to make it unfit for consumption, by adding methanol or xylene, or illegally home-distilled alcohols, can and does cause blindness, brain damage and/or death.

• • n-Hexane -

• Looks to be compliant.
• I suspect that this has been included as a modern-day example of a chemical used in industry that has the potential to cause neurotoxicity. Should this be explicitly stated? Prior to concerns over "global warming" and "green house gases" other chemicals such as carbon disulphide, dinitrobenzene and dinitrotoluene would have been found in the workplace and they are also neurotoxic.

• • Endogenous neurotoxin sources -

• Looks to be compliant.

• Scope -

• Should substances that cause the inhibition of acetylcholinesterase be included and given a subsectionpf their own? In the Background section states the organophosphates, such as DDT and sarin gas, can cause/interfere with it, but there seems to be no further mention of this topic? Note: the Tetrodotoxin sub-section does discuss the use of two acetylcholinesterase inhibitors as a means of enhancing survival after exposure to a certain neurotoxin.

• WP:Lead -

• This should both introduce the topic of the article and also provide a summary of the main points in the article. The requirements can be found in WP:Lead.
• In general the lead appears to be compliant, but I have some concerns over the last sentence: Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant,[9] antitoxin[19] and ethanol[20] administration., as this does seem to lack balance against what is given in the body of the article. Very many of the subsections have no mention of treatments, but some do. I've not noticed one that mentions ethanol administration as a treatment and, as far as I can see, "ethanol" is only mentioned in the "ethanol" sub-subsection of Neurotoxins with multiple effects. Some neurotoxins seem to kill so fast that treatment (let alone diagnostic tests and then treatment) may not be possible.

At this point I'm putting the review "On Hold". The article has many strong points in favour of it being made a GA, but the "problems" that I've raised above need to be consider and addressed first. Pyrotec (talk) 17:08, 23 December 2012 (UTC)

Nothing's been touched since your hold was added, so failing this. Wizardman 23:54, 13 January 2013 (UTC)