Ricin: Killer of Cancer or Killer of People?

Popularized by the hit TV show Breaking Bad, the protein Ricin is well known as one of the most common and toxic biological molecules. In a recent review published in the journal Toxins by Letizia Polito, the dangers and possible therapeutic effects are covered as well as the mechanism of action. Traces of ricin have been found as long as 24,000 years ago in a purified form and have been present in medical use dating as far back as 1500 B.C. in Egypt. Coming from the castor oil plant, the castor bean presents a source of easy purification which has led to added fear of Ricin. This combination has led to Ricin being labeled as a Category B substance. As for its bioterrorism capabilities, the toxin becomes impractical as eight tons would have to be aerosolized over a 100 km2 space for a 50% casualty, as compared to anthrax which requires only one kg for the same effect. However, ricin has been shown to inhibit cellular protein synthesis by 50% at doses from 0.1-1 pM, meaning it would be lethal in humans from ~5-10 chewed beans. Medically, Ricin has proven its worth as a laxative, diuretic, anti-inflammatory, and abortifacient, with promising research as an anti-cancer therapy. Due to its non-specific binding mechanism Ricin requires a carrier, typically an antibody, to form a conjugate called an immunotoxin. These immunotoxins have been shown in both pre-clinical and clinical studies to be effective toward different cancer types both in vitro and in vivo for humans. Part of the continued negatives of these treatments are the continued unspecific toxicity, organ toxicity, immunogenicity, fast removal from blood stream, and lysosomal degradation inside cells. 

Ricin falls under the category of a “ribosome-inactivating protein” (RIP), and is specifically a Type 2 RIP. This means the protein contains two different chains, with the B-chain allowing easier entry into cells, making it potentially more dangerous. The mechanism of action for Ricin is the deletion of a single adenine base from the large subunit ribosomal sarcin-ricin RNA loop (SRL). This deletion of a highly conserved structure leads to a blockage of GTP hydrolysis and impedes translational machinery. This impeding of translational machinery appears to be what leads to cell, and organism, death.

Despite the bad name Ricin gets as a toxin, the possibility as an anti-cancer therapeutic lends itself to being a protein worth continued research.

Reference

Polito, L., Bortolotti, M., Battelli, M. G., Calafato, G., & Bolognesi, A. (2019). Ricin: An ancient story for a timeless plant toxin. Toxins, 11(6), 1–16. https://doi.org/10.3390/toxins11060324

The Impact of Energy Drinks on Adolescents

 Energy drinks have been surrounded by multitudes of controversial information as they include caffeine which is generally recognized as safe (GRAS) by the FDA. Energy drinks have been known to help adults stay awake as well as endure throughout a day. For children and adolescents however, data has shown age to be a critical factor in rating the severity of toxicity in taurine and caffeine. Aside from caffeine, which is needed to boost alertness and energy, taurine is another commonly included ingredient in energy drinks. It seems that for children there are negative risks associated with the ingestion of taurine and caffeine, especially since their brains are still developing. Another major reason that countries have limited the sale of energy drinks to minors is the due to the smaller body size and lack of tolerance to stimulants. Although brain development is at the core as to why children should not be ingesting energy drinks, another major issue is cardiovascular functioning. It has been found that acute effects of caffeine and consumption of energy drinks have shown moderate increases in blood pressure and heart rate.

 

Something that needs to be considered before giving adolescents and children access to energy drinks, is the idea that adults and children are in different stages of life. Adults are tasked with caring for others in the family or at least working while children are tasked with exploring the world and understanding it as they explore. The relative goals and requirements of both groups are typically different. One possible mechanism in which caffeine interacts with people is by enhancing cognitive abilities through changing general arousal levels, specifically in fatigued individuals. For an adult, the situation may be that they have more work do to whether that be physical or cognitive. In this case caffeine is useful, but for a growing child fatigue is an indicator of rest as opposed to an indication to ingest caffeine. This information suggests that the developing brain will show signs of hypersensitivity towards caffeine ingestion.

 

Since coffee has been around for longer, it is more established in our lifestyles than the ingestion of energy drinks. However, while energy drinks have been reported to have negative effects, companies are still targeting younger aged groups for consumption of such products. It is important to keep in the mind the total or inclusive impacts of all items being ingested. That is the inclusion of the harmful effects of coffee, which are not easily highlighted as publication bias supports coffee production and ingestion. Caffeine is one of the largest contributors to the negative impacts caused by energy drinks, but it is crucial to remember the sum of all of the ingredients which produce such effects rather than one single factor.

 

 

Source

Curran, C. P., & Marczinski, C. A. (2017). Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain. Birth defects research, 109(20), 1640–1648. https://doi.org/10.1002/bdr2.1177

The Power of a Smile...even with masks on

2020 has been a tough year so far, but let's turn that frown upside down. Recently, at the University of South Australia, it was confirmed that smiling can trick the mind into being more positive. Yet, in a pandemic world where no one knows what each other's chins look like, much less a pearly white grin, how can we attempt to use this evidence to improve attitudes for the better? The study, published in Experimental Psychology, showed that facial muscular activity alters both facial and body expressions which typically generate more positive emotions. According to lead researcher Dr. Marmolejo-Ramos "when you forcefully practise smiling, it stimulates the amygdala -- the emotional centre of the brain -- which releases neurotransmitters to encourage an emotionally positive state."

Now back to the issue of masks disguising our smiles... 

In my opinion, the implementation of masks has required me to focus more on what others are saying and improve eye contact to convey emotion and meaning. Masks make it more difficult to hear others, and certainly more difficult to see a smile. Fortunately, the human face has a multitude of muscles and several of those used to genuinely smile involve the eyes and forehead. Alas, we can confirm a sincere smile and happiness by observing the eyes even if the rest of one's face is covered! I believe this will allow us to practice beneficence because we are seeking to do the most good in lifting not only our own spirits, but those around us. Let's use this information to improve mental health everywhere.

Reference: https://www.sciencedaily.com/releases/2020/08/200813123608.htm ; https://econtent.hogrefe.com/doi/10.1027/1618-3169/a000470