After reading this article, I decided to do some math on the matter…and unless the person into whom the blood is being injected has incredibly low tolerance to heroin, the chances of getting a heroin high by injecting yourself with the blood of someone else who has just used heroin is near nil.

Let’s do some math. Once heroin is introduced into the body, it spreads systemically through blood (timing varies with method). Assuming a 1 gram IV dose and ~5 liters of blood in the average human:

main person’s blood concentration = 0.2 g/L

Now, according to the article, the amount of blood shared is about a teaspoon, or ~5 mL:

0.2 g/L * 5 mL = 0.001 g heroin being transferred

As you can see, the dose from blood is near negligible, as it’s been weakened a thousandfold–for an addict, this amount wouldn’t even be remotely enough to get a high. There are two scenarios in which this technique might be tweaked to work, but both of them will prove fatal to one or both parties:

• Main person takes a particularly heavy dose–they’ll likely suffer respiratory depression to the point of coma/death.
• More blood is used–main person could die if too much blood is drawn or the one accepting blood could suffer an immune response and die.

Why this practice is folly:

• bloodborne diseases
• immune responses from mismatched blood types
• other infections (from normal skin flora or dirty needles, particularly if someone has an immune system weakened by AIDS)
• …it just doesn’t work

Basically, the belief in this practice is due to placebo effect and maybe some residual heroin left over on the needle or in the syringe from the main user.

To understand HIV medication, one must first understand the 6 crucial steps that HIV needs to complete in order to replicate and spread. In order, they are:

1. Binding and fusion: HIV binds to either or both of two cell receptors known as CCR5 (typically in initial stages of infection) and CXCR4 (often in later stages) in order to enter the cell. HIV is surrounded by a lipid envelope that allows it to fuse with the target cell’s membrane, releasing the virus’s core contents into the cytoplasm.
2. Reverse transcription: HIV’s genetic code is RNA-based, so its reverse transcriptase enzyme generates a DNA template.
3. Integration: The DNA template is then integrated into the host cell’s genome.
4. Transcription: The host cell’s protein machinery transcribes and translates mRNA based on the integrated DNA template.
5. Protease cleavage: HIV proteins are initially made in large chains known as poli-proteins, which are cleaved into their functional pieces by proteases.
6. Assembly and release: New virions assemble at the cell membrane and bud from the cell surface.

DRUG CLASS 1: ENTRY INHIBITORS

CCR5 antagonists prevent the first binding step, stopping the virus from entering any cells. The problem is that this is only effective for patients whose variant of HIV solely relies on the CCR5 receptor for virility, so if a tropism test reveals a CXCR4-dependent virus, this option is not used.

• Maraviroc is the only FDA-approved drug in this class.
• Common side effect (CSE): hepatotoxicity (liver problems)

Fusion inhibitors allow the virus to bind initial receptors, but prevent the next step of fusion between the viral and cellular membranes.

• Enfuvirtide is the only FDA-approved drug in this class, and is given through subcutaneous injections.
• CSE: Injection site inflammation/redness in 90% of patients, usually mild.

DRUG CLASS 2: REVERSE TRANSCRIPTASE INHIBITORS

Nucleoside analogue reverse transcriptase inhibitors (NRTIs) compete with natural nucleotides, leading to premature DNA chain termination.

• Drugs: Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zidovudine
• CSE: Mitochondrial toxicity from inhibition of the enzyme responsible for mitochondrial DNA synthesis.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to the reverse transcriptase enzyme, inhibiting its function.

• Drugs: Delavirdine, Efavirenz, Etravirine, Nevirapine
• CSE: Rash, hepatitis

DRUG CLASS 3: INTEGRASE INHIBITORS

These inhibit incorporation of viral DNA into the host’s genome.

• Raltegravir is the only FDA-approved drug in this class.
• CSE: muscle damage/problems

DRUG CLASS 4: PROTEASE INHIBITORS (PIs)

PIs inhibit viral proteases from cleaving viral poli-proteins into their functional bits, preventing assembly of the virus.

• Drugs: Atazanavir, Fosamprenavir, Darunavir, Indinavir, Lopinavir, Nelfinavir, Saquinavir, Tipranavir
• Ritonavir is a PI that is frequently used in low doses for its interesting effect of preventing metabolism of other PIs–increasing their efficacy.
• CSE: Many possible–nausea, vomiting, diarrhea, hepatitis, etc.

TREATMENT REGIMENS

Treatment regimens vary widely based on the patient, the progression of the disease, the strain of HIV, etc. Broadly speaking, initiation of therapy in treatment-naive patients often begins with one of the following 3-drug combos:

• 2 NRTIs + 1 PI (usually boosted with ritonavir)
• 2 NRTIs + 1 NNRTI
• 2 NRTIs + 1 integrase inhibitor

The idea is to prevent further spread of the virus in the patient with a cocktail to prevent easy resistance mutations. Some of the many things to consider to individualize the treatment for each patient:

• patient preference
• toxicity profile
• child-bearing potential (women)
• strain’s baseline resistance(s)
• does the patient have other conditions that require treatment? (drug interactions)

Key to the regimen are regular check-ups which evaluate adherence to treatment, potential psychological concerns, side effects/complications, resistances, etc. Patients are counseled on prevention of HIV transmission and opportunistic infections, as well as other health changes that might be appropriate.

Nota bene: HIV/AIDS research is a very active field, and the above information could change at any time!

Disease (insect): notes.

1. yellow fever (mosquitoes): Mortality rate is high.
2. dengue fever (mosquitoes): This is the most common insect-borne viral disease in the world. Classic dengue (a.k.a. breakbone fever) is rarely fatal and has few aftereffects, but dengue hemorrhagic fever is much more severe, with ~10% fatality rate.
3. eastern equine encephalitis (mosquitoes): ~50% fatality rate, with usually severe central nervous system problems for survivors.
4. western equine encephalitis (mosquitoes): ~2% fatality rate, but inapparent infections outnumber the apparent ones at least 100:1.
5. St. Louis encephalitis (mosquitoes): ~10% fatality rate, but most infections are inapparent.
6. California encephalitis (mosquitoes): Clinical can be mild to severe, but death is rare.
7. West Nile Virus (mosquitoes): Less than 1% of those infected have symptomatic disease.
8. filariasis (mosquitoes): While the microfilariae (which do not cause symptoms) can be treated with the drug diethylcarbamazine, there is no drug therapy for the adult form of this of this nematode which can cause elephantiasis with repeat infections.
9. Colorado Tick Fever (wood tick)
10. Chagas’ disease (reduviid bug): The acute form can be treated with nifurtimox, but there is no effective drug against the chronic form, which causes myocarditis and megacolon.

All information derived from study of Review of Medical Microbiology and Immunology, authored by Dr. Warren Levinson.

HIV = Human Immunodeficiency Virus
AIDS = Acquired Immunodeficiency Syndrome

In common use, the terms HIV and AIDS are often used interchangeably.

The distinction is made clinically because infection with HIV typically doesn’t immediately cause AIDS, strictly speaking–it can take several years for the presentation of AIDS to become apparent. Because of this, it’s estimated that ~25% of those with HIV/AIDS in the U.S. are unaware that they are infected.

The conundrum is that upon infection with HIV, many of the initial symptoms can be vague: fatigue, low grade fevers, night sweats, weight loss, and intermittent diarrhea are common, but all of these symptoms have many, more frequently seen causes, so unless some risk factors are apparent in a patient’s history, it can be missed*. Hence, many institutions are now adopting the policy that separate written consent is not required for testing, and implementing the highly-recommended opt-out strategy, particularly for pregnant women.

HIV causes a deficiency in an immune cell that is identified by the presence of a marker protein known as CD4, and in 1993 the surveillance case definition came to include that a patient has AIDS if their CD4 count in a lab sample dropped below 200. There are various other tests now in use to confirm infection with the virus, but as far as I know, that was the first clear-cut definition.

* There are also numerous circumstances where the patient may not feel comfortable discussing their sexual history.

If you really feel the need to be saturated with vitamin C “just in case”, your blood level hits maximum at ~400 mg/day; anything above that is peed out, so don’t waste your time and/or money!

Sources:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC55540/
http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/

Something else to consider that I learned in my renal course: 2000 mg per day of Vitamin C supplement increases urine oxalate (a component of a common variety of kidney stone) by 22%. Men who take 1000 mg or more vs. the RDA of 90 mg have up to 40% higher risk of stone formation. So people who are either at risk of forming calcium oxalate stones or have a history of forming them should be instructed to stop vitamin C supplements.

Mind you, everyone’s risk for forming kidney stones is widely different, so just take the above as a cautionary note of something to keep in mind.

I went to an evolutionary biology talk they had at my school (to celebrate Darwin’s birthday) about the fact that a lot of parasites secrete hormones that suppress a human’s immune system, and that our immune systems, without the parasites, are a lot stronger than they really need to be, as a result of co-evolution.

The point of the talk was that they were experimenting with some kind of parasite (I think pigworm?), chosen for its production of these types of hormones, and its relatively significant safety for humans (can’t reproduce in our systems, have no real ill effects, just kind of hang out and live quotidian parasitic lives secreting these hormones), as a possible treatment for autoimmune diseases.  I seem to remember they had some striking results for Crohn’s disease, but I’m not completely sure.

I think there was a Radiolab episode where they discussed this too.  I think it was called “Parasites.”

~~~ BACKGROUND ~~~
The idea of using parasites to treat autoimmune conditions is a variant of the Hygiene Hypothesis. Put simply, it states that modern industrialized society has become so clean that we’ve disrupted the “natural” balance of cleanliness/dirtiness. Now that we’re all fans of everything being antibacterial/antimicrobial, our immune systems just aren’t constantly under siege. In other words, they’re bored. So without the constant risk of infection keeping them well-disciplined, they start gnawing on the body by mistake.

There is the unfortunate truth that our immune systems, once activated, have absolutely pathetic negative feedback loops. Every other system in the body, from respiration to endocrine to digestive, has signaling pathways in place that, in a healthy individual, allow for surprisingly fine control of homeostasis. The only equivalent that has been elucidated in the immune system is the small quantity of T-regulatory cells, and no one seems to be capable as yet of explaining their origin, what determines who has how many, who has fewer/defective ones, etc. There are a few other factors such as controlled apoptosis/anergy of self-reactive immune cells, but at the moment they’re not too inspiring since they can be overturned. :-/

So it makes sense, then, that with limited endogenous resources to calm down the immune system, an external source may have provided this need for millenia. What better than buggers who evolved to evade the immune system?

~~~ SUPPORT ~~~
A quick scan of clinical trials and pubmed reveals that hookworm species are being used for everything from Celiac to Crohn’s to multiple sclerosis.

http://clinicaltrials.gov/ct2/show/NCT00671138?term=parasite+autoimmune&rank=1
http://clinicaltrials.gov/ct2/show/NCT00630383?term=parasite+autoimmune&rank=4
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856386/
http://www.ncbi.nlm.nih.gov/pubmed/14499784

The current work in the literature appears to be generally in favor of at least trying this approach for those who qualify, and anecdotal evidence, as seen by the gentleman who appeared on the Radiolab episode and told his tale about asthma, is wildly supportive.

In short, it’s possible that for people who simply have environmental (nurture, not nature) causes of autoimmunity, this might well be their miracle “drug”.

~~~ CONCERNS ~~~
One of the main reasons this relatively new approach has been able to make it to clinical trials so quickly is precisely because of its extremely attractive side effect profile. The worms are pretty easy to treat if anything goes wrong or the treatment doesn’t work, so patients aren’t at particularly severe risk for trying it. Hence the question arises–are we just blindly praying for luck and seeing a placebo effect?

I ask because dosing clearly needs work, as you want to give the patient a sufficient load to suppress the immune system, but not enough to cause anemia. How that will be determined for each individual (remember, autoimmunity has various levels of severity) has yet to be properly established, and work is coming out suggesting that the body can tolerate a higher load than initially suspected before therapeutic benefits are viable: http://www.ncbi.nlm.nih.gov/pubmed/20030661

Furthermore, at a more molecular level, parasitic presence isn’t necessarily just about immune suppression–they induce a shift in the immune system’s style from Th1 to Th2 because of the specific cocktail of molecular signaling required to destroy a helminthic parasite. The bizarre conundrum here is that an overactive Th2 response is associated with allergies. Wait. Autoimmunity != being allergic to the body?!? If that’s the case, will treating with parasites cause these people to start developing severe allergies? No one knows–this technique is just too new for any longitudinal studies to be conducted with legitimacy.

This approach also doesn’t really encompass the multifactorial etiology of autoimmunity, and ignores the genetic susceptibilities entirely. For instance, this would do nothing for people with autoimmune polyendocrine syndrome, which is an irreversible defect in the AIRE (autoimmune regulator) gene. Acute infections can also be a cause for autoimmunity, as some bacteria attempt to trick the immune system by presenting proteins similar to those found in the body. It’s all fine and well that our immune systems can tell the fine point differences until the infection is cleared and all these immune cells are seeing endogenous things that look mighty close to to the thing they were killing just days ago (example: infection by Campylobacter jejuni has been associated with Guillain-Barre).

At the end of the day, remember that just because something co-evolved with us doesn’t mean we’re symbiotes. While I suppose from an evolutionary perspective our hygiene has essentially killed off any possibility for such parasitic symbiosis to evolve, the fact remains that plenty of people who aren’t infected with parasites aren’t suffering from autoimmunity, and the advent of modern hygiene came with an overwhelming and undeniable jump in life expectancy. It may be that for this niche population, it’s an efficacious treatment, but I certainly wouldn’t advocate infecting everyone with wormies!

The specific leader is debatable based on region, as well as age ranges within the adult population. According to the WHO, cataracts take the lead worldwide, while the AOA states that it’s diabetes.

Sources to check out for more detail:
http://www.utsouthwestern.edu/utsw/cda/dept28070/files/153528.html
http://www.nlm.nih.gov/medlineplus/magazine/issues/summer08/articles/summer08pg14-15.html
http://www.who.int/blindness/causes/en/
http://www.aoa.org/x6814.xml

• In the 1920s, Karl Lashley proved that neurons all over the brain are involved in memory, and that there is no specific storage area per se, although it turns out some structures are more intimately involved than others, such as the hippocampus, amygdala, inferotemporal cortex, prefrontal cortex, and mammillary bodies.
• In long term potentiation, the foundation of a memory is a structural change in the neural network involved–a physical strengthening/proliferation of the neuronal connections that improves with each consecutive recall of a given memory. Donald Hebb first proposed this in 1949, and it’s been the working model ever since.
• When a neural network fires, neurotrophins (such as Neural Growth Factor, or NGF) are released each time, and so if a memory is not used, the synapses involved weaken as the neurons quickly divert their synapses to other incoming stimuli. Broadly speaking, memory follows Ribot’s Law (1881): older memories are more stable due to frequent recalls while recent memories are more likely to be lost. For you computer scientists, it’s analogous to a stack: first-in, last-out.

An analogy: you (a neuron) have 500 friends (connections/synapses) on facebook (the brain). You’ve got your close group of 20 friends now that you hang out with all the time (a memory), but then for whatever reason, they stop returning your calls, e-mails, texts, etc. (memory’s not being used; synapses weaken) So you reach out to some people you haven’t seen in a while (beginnings of another memory), and while a few don’t bother replying (synaptic attrition–happens all the time), some do, and you strengthen your relationship with them (voila! new memory). This comparison is particularly apt given that the longer you’ve known someone, the more likely it is you’ll stay in touch with them no matter what happens. It also follows the fact that neurons always have some connections to other neurons not involved in a memory, and thus always have competing linkages to fall back on.

Side note: an extremely interesting consequence of this structural basis is that when a memory is actively being recalled, it is susceptible to erasure. When a memory is retrieved from long term memory, it is temporarily held in short term memory, and concussions/electric shocks can actually cause posttraumatic amnesia of even the long-term memories.?

Before you start to vocalize, you automatically trigger your pre-vocalization reflex, in which cranial nerve VII contracts the stapedius muscle to pull on the stapes in your middle ear, and simultaneously, cranial nerve V contracts tensor tympani to pull on the malleus which tightens the tympanic membrane. This effectively dampens how you hear your own voice.

This is the main reason why you sound so different to yourself when you hear a recording of your voice–you are finally hearing yourself without an operant pre-vocalization reflex. This also explains why patients with Bell’s palsy (lesion/damage in cranial nerve VII) often present clinically with the complaint that they suddenly sound different to themselves.

=== Background ===

There 2 physiologic reasons why your joints make noise[2][3]:

1. Gases: Your joints are lubricated with synovial fluids, which contain oxygen, nitrogen, and carbon dioxide. When you bend or manipulate a joint in certain ways, you can stretch the joint capsule, causing rapid release of gas that makes a sound as it forms bubbles. You can’t re-pop a joint this way until that gas is reabsorbed into the fluid–this is why you have refractory periods for some joints after you pop them.
2. Movement of the mechanical components: When a joint moves, the associated tendons’ positions change, and a snapping/cracking sound is common in the knee or ankle as tendons move back and forth. If you are able to continuously “re-pop” a joint without a refractory period as above, this is likely what is happening.

=== Is it bad for you? ===

According to Johns Hopkins Orthopaedic Surgery, “cracking and popping of joints is usually normal and most of the time is nothing to be concerned about…There are no long term sequelae of these noises, and they do not lead to future problems. There is no basis for the admonition to not crack your knuckles because it can lead to arthritis.”[4] Studies have confirmed that knuckle-cracking, at least, doesn’t seem to do any long-term harm[5].

I haven’t yet seen contrary evidence that can’t be differently explained. The Library of Congress site claims that “studies show that repetitive knuckle cracking can do some damage to the soft tissue of the joint. It may also lead to a weak grip and a swelling hand”, but it could theoretically be explained by excessive wear-and-tear from other causes such as job-related injury, weak joints, weak supporting muscles, inflammatory conditions, age, etc, and as I don’t know what the original research papers are, I can’t look them up.

=== So when should I worry? ===

There are numerous instances where the popping/cracking of a joint is not normal, and in such cases care should be taken not to stress the joint any further by unnecessary manipulation. Some scenarios to consider:

• Pain. This is the ultimate common denominator to be wary of, and indicates a (usually structural) joint problem that needs to be treated.
• Arthritis. Arthritic joints make sounds caused by the loss of smooth cartilage and roughness of the joint surface as bone (often painfully) grinds on bone.
• If the joint gets locked or stuck when it pops or cracks, it’s possible that something is caught between joint surfaces, such as a torn/loose piece of bone or cartilage. Once a joint is stuck in this way, it may need to be wiggled around to unlock it, causing a pop.[6]
• “A popping sound is also a common contemporaneous event with a serious rupture of a ligament or a tendon. Such occurrences are usually painful, but not exclusively so. A popping sound is often experienced by athletes who sustain an anterior cruciate ligament (ACL) tear, an Achilles tendon rupture, or a rupture of the hamstring. The pop is caused by the structure being torn completely in two.”[7]
• Swelling. This is not normal, and should be evaluated if it accompanies the noises.

[1] Meaning, your joints don’t suffer from inflammatory conditions or any other underlying conditions that inherently stress or damage the joint, and you don’t have any inherent genetic susceptibilities to joint damage, etc.
[2] Adapted from the Library of Congress: http://www.loc.gov/rr/scitech/mysteries/joint.html
[3] Additional resource: http://www.jaoa.org/cgi/reprint/102/5/283
[4] http://www.hopkinsortho.org/joint_cracking.html
[5] http://www.scientificamerican.com/article.cfm?id=crack-research
[6] http://www.orthop.washington.edu/uw/arthritisbasics/tabID__3376/ItemID__180/PageID__348/Articles/Default.aspx
[7] http://www.faqs.org/sports-science/Je-Mo/Joint-Noise-Popping-and-Cracking.html