Clinical Toxicology

Clinical Toxicology

  • Reza Heidari added an answer:
    Can phenytoin, carbamazepine and nevirapine form covalent bond with cellular proteins in native form or metabolite form?

    Can anyone help me in clearing my doubt whether the anticonvulsant drugs like phenytoin, carbamazepine and anti-retroviral drug nevirapine can act as haptens or can they form any covalent bond with any of the extracellular or intracellular proteins either in native form or in metaboilte/hapten form before/during exerting its mechanism of action or they can form any hapten-like molecule during conjugation process in kidney for elimination which can induce immune reaction? Any literature describing the phenomena has been published on this? Please share it here to me...

  • Paul Dessauer added an answer:
    What evidence exists that novel synthetic cannabinoids may act in a clinically signficant fashion at receptor sites beyond CB1?

    G'day,

    The synthetic cannabinoids (SC) currently being marketed as alternatives to plant cannabis have a higher risk of adverse outcomes than phyto (plant) cannabinoids.

    The SC products on the market are much stronger agonists at the CB1 receptor than THC, and none contain a synthetic equivalent to the phyto-cannabinoid CBD, but is part of the increased risk also due to SC substances acting at other receptor sites?

    Paul Dessauer · WASUA

    I've just been sent this Annals of Pharmacotherapy article, which mentions the same hypothesis in a footnote;

    <<< One potential concern with synthetic cannabinoids is the
    possibility of serotonin syndrome. JWH-018 and similar
    synthetic cannabinoids contain an indole moiety, similar to
    that of serotonin, and therefore theoretically could increase
    serotonin receptor activation18 (Figure 1 19,20). Also, it has
    been suggested that synthetic cannabinoid compounds may
    have weak monoamine oxidase inhibition at high doses,
    further increasing the risk of serotonin syndrome. >>>

    I've attached a PDF of the article (Wells). The footnote referenced another article (El-Subbagh, also attached) that investigated the relevance of an indole moiety in non-SC compounds and concluded it played a major part in bio-activity.

    Once again the Wells article is an well-educated guess, but not evidence...

  • Paul Dessauer added an answer:
    Synthetic cannabinoids- what evidence exists regarding potential for inducing acute or chronic problems with physical or mental health?

    A wide variety of synthetic cannabinoids (SC) are now being marketed as "safer" or "quasi legal" alternatives to plant cannabis.

    Anecdotally, it appears that these research chemicals are typically associated with a significantly higher risk of acute adverse responses (such as tachycardia, anxiety attacks and transient psychosis) than smoking "real" plant cannabis.
    As the majority of SC products being marketed contain chemicals that are much stronger cannabinoid receptor ligands than THC, (and some contain mixtures of more than one SC), and as these mixtures do not contain any equivalent to CBD, this is perhaps not surprising.

    Does anyone know of animal studies or case histories relevant to the potential of these chemicals to induce such acute problems?
    I am also keen to find any research that may indicate the potential for dependence, and likely withdrawal profiles upon abrupt abstinence from regular use, of these chemicals.

    <<< The intravenous administration of THC may be associated with a range of schizophrenia-like positive and negative symptoms in psychosis-free individuals (D’Souza et al., 2004).

    Conversely, the phytocannabinoid CBD presents with anxiolytic and antipsychotic properties (Zuardi et al., 2006), possibly because CBD may displace the binding of THC from CB-rs.

    In contrast, spice products contain no CBD, and the SC chemicals are full agonists at CB-rs and are characterized by both a receptors’ higher affinity and higher potency in comparison with THC (Fattore and Fratta, 2011; EMCDDA, 2011).
    Forrester et al. (2012) showed that a “cannabis”-associated psychopathological syndrome occurrence was less likely with marijuana than with SC, with 2% in the marijuana and 11.2% in the SC misusers’ group, having been identified as experiencing hallucinations and delusions.

    Those experiencing psychotic episodes related to Spice use are also reported to present with higher/more frequent levels of agitation and behavioral dyscontrol in comparison with those psychotic episodes described in marijuana misusers (Brakoulias, 2012). >>>

    “Spiceophrenia”: a systematic overview of “Spice”-related psychopathological issues and a case report
    http://onlinelibrary.wiley.com/doi/10.1002/hup.2312/abstract
    .
    Thanks.

    Paul Dessauer · WASUA

    I've just posted a related question here;

    https://www.researchgate.net/post/What_evidence_exists_that_novel_synthetic_cannabinoids_may_act_in_a_clinically_signficant_fashion_at_receptor_sites_beyond_CB1?_tpcectx=profile_highlights

  • David Ogbonnaya Onu added an answer:
    Methadone poisoning in an addict?
    How to determine lethal methadone concentration in an addict when one doesn't know the amount of pills taken each day?
    David Ogbonnaya Onu · The Royal Hobart Hospital

    I agree with the 2 responders about combining the severity of symptoms and hair analysis. The latter test quantifies the duration of Methadone use. Urine toxicological testing is only qualitative. 

  • Vincent Bloks added an answer:
    Can I give DMSO to a rat as a solvent?

    Hi all, please give me a hand. I am going to use glibenclamide (from Sigma) to treat diabetic rats as a positive control for my extract. I would like to know which solvent is suitable for dissolving glibenclamide before oral administration. I searched some papers and they use DMSO, however I don't know the concentration of DMSO. May I use the absolute one for rat feed? Or can I use another solvent (which, ?%). Thank you so much!

    Vincent Bloks · Universitair Medisch Centrum Groningen

    perhaps dissolve in DMSO and then in oil ( cremaphore 10%) , perhaps that will work

  • Yvonne Hopf added an answer:
    Does anybody know a different solvent than DMSO for Everolimus?

    Background: it needs to be solved for IV administration to pavians and the current information we have is that it is soluble in DMSO (dimethylsulfoxid). If you don't know a different solvent maybe someone knows a little more about 'safe' concentrations for administration. Many thanks for your help!

    Yvonne Hopf · Ludwig-Maximilian-University of Munich

    Thanks David!

  • Nikola Ilankovic added an answer:
    What makes titanium implants toxic and cause allergic and autoimmune reactions?
    Dental implants are made of titanium because of biocompatibililty. Dental implants give titanium toxicity allergic and autoimune reactions.
    Nikola Ilankovic · University of Belgrade

    Thank You Rafael!

  • Ludwig Gruber added an answer:
    Does anyone know which plastic products contain the most phthalates?
    With phthalates being measured at higher levels in human biomarkers and being used increasingly in food containers and other products, has anyone examined the products that expose humans the most/least? Presumably those with the least amount of polyvinyl chloride, but is it so? Is there any relationship to the plastic recycle numbers?
    Ludwig Gruber · Fraunhofer Institute for Process Engineering and Packaging IVV
    Plasticised PVc is without doubt the most likely plastic material with high phthalate content. The exposure especially to DEHP from food consumption alone can be in the range of the TDI. And there are a number of other sources which contribute to the overall human exposure. Therefore there is indeed a problem, but we do not observe phthalates increasingly in food containers and other products as You suggest.

    Direct contact between PVC and food is not really the predominant scenario for phthalates contamination. It seems that the ubiquitous presence of the phthalates and their lipophilic character are more important.

    There is no direct relationship to the overall plastic recycle numbers, things are more complex. A contamination with phthalates is only likely for some kinds of plastics, and these are normally not used as food contact materials. Again, the high production numbers and the resulting ubiquitous presence of the phthalates are more important.
  • Rahman Maman added an answer:
    What are the current methods for determining the median lethal dose (LD50)? What are the advantages of these methods to "Lorke's Method"?
    Lorke's method has been used since 1983.
    i wonder if the method (UDP) can be applied for the fishes since we know this oral administration for the rat/mice.. anyone can suggest me?
  • Richard Beasley asked a question:
    Should IRM drugs containing imiquimod be patient applied drugs?
    IRM's are very unpredictable and result in non-specific immune responses toward antigens and rogue cells that are not well defined nor well understood which can lead to catastrophic events occurring in certain segments of the patient population. Imiquimod is one such small-molecule IRM that causes over a dozen cytokines to be induced by their respective origin of production during their physical contacts with molecules of this drug. During treatments, the users cannot separate themselves from the physiological influences of the ongoing, out of sync, induction of this family of cascading cytokines being induced at unknown and unregulated levels within their bodies during each patient applied application of the drug. As with injection or IV chemo treatments where body weight and rate of drug deterioration after injection is factored into safety profiles for the individual patient, IRM's such as imiquimod do not possess this safety feature and are actually causing unknown or "free-wheeling" pharmacological effects within each user that are increasing the levels of cytokines during the weeks of treatments rather than systematically reducing them over time as we see in traditional chemotherapies. Drug induced autoimmunity is the number one possibility surrounding these IRM's.
  • Henning Thole added an answer:
    Why isn’t clinical toxicology a more significant part of medical school education?
    With abundant evidence in the literature that many health afflictions result from toxicant exposures, and with published NHANES data from CDC that most people have bioaccumulated numerous persistent toxicants within their body, why are medical students not taught about clinical toxicology and approaches to investigate and treat toxicant-related health problems?
  • How to convert a toxic dose for a zebrafish to be equivalent to the one for rats?
    I want to use the toxic dose for a rat. I want to ask if I can use the dose without changing anything or do I need to make a certain conversion of the dose for zebrafish to be equivalent to the one for rats?
    Gabriela Rodríguez-Fuentes · Universidad Nacional Autónoma de México
    Uhmmm I don't think there is a direct way to convert toxic doses between species. Each species have their own peculiar physiology. You'll need to standardize your dose in each species then, calculate your toxicological parameters for each species and then compare. Please be very careful when interpreting your data because usually zebrafish is exposed to toxicants in water and you don't have a "dose" but an exposure concentration.
  • Andrzej Szymanski added an answer:
    Does anyone know useful biomarkers of hepatic steatosis?
    Generally, the echo analysis is clinically used for diagnosis of steatosis (fatty liver). I would like to know any other tools or biomarkers to detect steatosis in the preclinical or clinical study?
    Andrzej Szymanski · Poznan University of Technology
    I think that the following links will be useful to you:
    http://onlinelibrary.wiley.com/doi/10.1002/lt.21875/full
    http://care.diabetesjournals.org/content/early/2012/08/24/dc12-0277.abstract
    http://www.biomarkerres.org/content/pdf/2050-7771-1-7.pdf
    http://www.owlmetabolomics.com/publicaciones/Hepatology% 20biomarcadores.pdf
  • Kenza HAMMOUDI asked a question:
    Can anyone help me with the therapeutic dose of apocynin against cardiotoxicity in mice?
    Apocynin against doxorubicin cardiotoxicity
  • Jerold A Last added an answer:
    Can activated charcoal be linked to a specific antibody to increase its anti-toxicity properties?
    In toxicology, activated charcoal is one of the therapeutic choices, but it still remains non-specific. What about linking activated charcoal with a monoclonal antibody to improve its properties?
    Jerold A Last · University of California, Davis
    There are a number of chelating agents that will bind lead and help remove it from the body. Try a Google search on "succimer" to get started.
  • Eldho Raju asked a question:
    Any body performed any toxicological studies on LEPTADENIA PYROTECHNICA?
    Any idea about the supplies for plant or plant extracts?
  • Alfonso Peña added an answer:
    What are the toxicological hazards for police dogs involved in drug detection?
    Particularly with respect to exposure, risks and hazard analysis of cocaine intoxication in dogs and cats.
    Alfonso Peña · Sociedad Colombiana de Toxicologia
    Aunque no estoy tan seguro, yo esperaría que el perro terminara algo adicto y creo que se pueden utlizar otros animales. Se asume que el método es el de acción/recompensa.
  • Rafał Skowronek added an answer:
    Do you know a case of fatal vinorelbine poisoning?
    Two months ago I made an autopsy on a patient poisoned of vinorelbine. I would like to publish this case, and I'm looking for similar cases.
    Rafał Skowronek · Medical University of Silesia in Katowice
    Hmm, I did not find any fatal cases of vinorelbine poisoning but according to the mechanism of action it should be similar to vinblastine.
  • Apurva Kumar added an answer:
    How specific and sensitive is the ELISA Measurement of Stachylysin in Serum to Quantify Human Exposures to the Indoor Mold Stachybotrys Chartarum?
    The current scientific consensus of the federally endorsed evidence, e.g. WHO (2009) Guidelines for Indoor Air Quality: Dampness and Mould, suggests that there is an association between persistent excessive indoor exposure to toxic mold and chronic respiratory tract illness (CRTI). Whilst this federally endorsed evidence is used to underpin guidelines on how to prevent or minimize these associated health risks, a causal relationship between excessive toxic mold exposure, for example, to Stachybotrys chartarum (SC), and CRTI in humans has not been verified.
    Apurva Kumar · National Institute of Mental Health and Neuro Sciences
    If commercial kits are available, these info will be supplied with kit.
  • Kerry Hassell asked a question:
    I am working on an assay for Docetaxel, has anyone worked with the stability of this compound, and can suggest a solvent it is happy in?
    Docetaxel assay - solvent choice

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