Study group discussion: Zidovudine

Review questions!

Full form of HAART?

Highly active anti retroviral therapy.

Which is more toxic.. Zidovudine or acyclovir? And why?

Zidovudine due to bone marrow suppression.

Yes! It causes BM suppression.

Actually, both of these drugs cause it..but zidovudine causes it at a much severe level.
Acyclovir and zidovudine have to be activated to their respective triphosphate. Zidovudine uses the host cell enzymes for this but acyclovir uses the viral enzyme FIRST and then the host cell enzyme. Hence in cases of zidovudine the toxicity is very high.

Wow what a concept!

The myelosuppression is so bad.. That you have to give blood transfusion and growth factors.

It effects the mitochondria of the cells too I guess.

AZT induces significant toxic effects in humans exposed to therapeutic doses...
Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H9 cells...
The toxicities explored here suggest that the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage.

Study group discussion: HNPCC (Lynch syndrome) and microsatellite instability

Just was mentioned in lecture: What is the cause of lynch syndrome (the specific cause)?

It's HNPCC. DNA mismatch repair affected.

Yes, a bit more specific! Which part of MMR?

I think it's micro satellite instability or MSH2.

Msh2 is one of them, correct!

MLH1 as well.

Mhmm. One more?

Donno any more T_T

Apparently MSH6 as well :)

Could you sum them all up? What is lynch syndrome..What are it's features?

Ovarian, Colon and Endometrial carcinoma are the features. You do the molecular talk!

Lynch syndrome (also known as HNPCC) increases the chance of colon cancer up to 80% along with increasing chances of other sorts of cancer.

It is caused by disruption of Mismatch Repair system due to mutations in 3 MMR factors : MSH2, MSH6, and MLH1

What about the microsatellite instability pathway? Which syndrome was that?

Oh I found out.. Microsatellite instability is found particularly in cells which are expressing mismatch repair defects. HNPCC is one of the of the most important syndromes where this happens. However its not an "exclusive feature" of MMR defects.

The microsatellite  instability is the evidence that the MMR isn't working properly and can't detect insertion-deletion loops that forms in the S phase. Googled and paraphrased.

Ah makes sense. Thanks!

Elaborate on the term microsatellite instability.

Umm it's kind of complex.. Usually you detect DNA by PCR, right?

Yup. You amplify the DNA!

So if while PCR, little microfragments of DNA split up which weren't there originally. They are called microsatellites. They were made during PCR. So if those are created, it means the fragment has microsatellite instability.

So these are abnormal?

They occur naturally.. But usually detected by MMR and dispatched if MMR doesn't work...
They will be present!

Yep!

Got it. Thanks!

Study group discussion: Peutz Jegher's Syndrome

What's Puetz jegher syndrome?

Hamartomatous polyp with pigmentation on lips.

Study link! http://medicowesome.blogspot.ae/2014/10/tumors-of-colon-and-of-polyposis.html

Another life problem solved! Haha thanks!

Lkb1 is involved in PJS. How?

Peutz Jegher's Syndrome mnemonic:
Remember the initial letters of the disease - PJS.
P: Pigmented oral mucosa
J: Jejunal polyps
S: STK 11 defect
Thank you  IkaN!

Oh nice. LKB1 kinase activity is lost due to somatic mutations. In Peutz Jegher's Syndrome, that is.

Study group discussion: Mechanism of pulsus paradoxus in severe acute bronchial asthma

Which one of the following does not cause pulsus paradoxus?

a. Severe aortic regurgitation
b. Cardiac tamponade
c. Constrictive pericarditis
d. Acute severe bronchial asthma

Study group discussion: Aminoglycoside adverse effects and mnemonics

1. Name the adverse effects of aminoglycosides.

Nephrotoxic
Ototoxic
Vestibulotoxic

And? (This one is most commonly forgotten)

Study group discussion: Iron metabolism

In which form is iron absorbed?

Fe2+
Ferrous!

In which form is it stored?

Ferritin!
Fe3+

Study link! http://medicowesome.blogspot.ae/2013/11/ferrous-vs-ferric-mnemonic.html

In which form does heme contain iron?
Ferrous

Remember..Heme is always in the ferrous form when free..And in the ferric form when bound. In heme..it is an exception.
Others ferritin, transferrin..it is always in ferric form

Ohh. Interesting!

Antidote for choice for acute iron overdose?

Desferoxamine?

Yup. Desferrioxamine is given IV.. It is for acute iron overload.

Which antidote is preferred for chronic iron overdose then?

Oral drug.. Deferiprone.
Desferoxamin SC.

Study group discussion: Sickle cell anemia

Name the three crisis of sickle cell anaemia.

Aplastic crisis
Vaso-occlusive crisis
Sequestration crisis

What causes aplastic crisis?
Parvovirus B19

*doubt discussion*
In sickle cell anemia what analgesic do we use? I've heard that morphine can cause vasoconstriction and that would make it worse, but I'm not sure that's true.

Yup, opiates are used.

One cause of death in sickle cell anemia is acute chest syndrome, if I give the patient morphine (that has a secondary coronary vasoconstrictor effect) that will kill the patient.

Correct.

Acute chest syndrome is due to occlusion of the pulmonary vessels.

The major issue hear is to given oxygen to the patient..Cause hypoxia aggravates the whole situation.

So I'm not supposed to worry about Myocardial Infarction?

Not that I've heard of.

Doesn't it cause CHF?

"The acute chest syndrome may mimic CHF however it is uncommon." Says the internet.

New drug for SCA. Read in Harrison. Azacytidine.

Mechanism of action of azacytidine?

Azacytidine increases HbF production and reduces anemia in sickle cell disease.

There's a drug which blocks gardos channel in RBC membrane. It's under trials too. It's the one I was talking about.

The mechanism is interesting because it prevents dehydration of the RBC.. That's the cause of sickling.

I like the sound of it - Gardos channel.

It's a potassium channel!

A greek god!

Me too.. It guards the RBC!

Gargoyle ..thats what my mind said.

Haha. They were guardians too!

Another interesting thing.. An anti fungal we use also blocks this channel in vitro!

Study group discussion: Electrolyte abnormalities that cause QT prolongation

Which electrolyte abnormalities lead to QT prolongation?

Study group discussion: Gate control theory of pain

Just had my first class of pain physiology. I loved it!

What was the most interesting thing that you learnt in class?

Melzack and Wall's theory. About the gate control of pain. I had to google the english term lol.

Aw that's so nice of you. It's an interesting concept. Why soldiers don't feel pain when they are injured in battle.. But feel it in the hospital.

What is it called in Brazilian? (I donno what language you'll speak)

Portuguese. In portuguese, it's 'teoria das comportas'

I feel better now for not recognising "Melzack and wall's theory" but I do remember learning teoria das comportas!  hahahaha I have to Google the translation all the time too.

Must be because of increase in Endorphins and adrenaline?

Not exactly. You should read more about it!

The brain determines which stimuli are profitable to ignore over time. Thus, the brain controls the perception of pain quite directly, and can be "trained" to turn off forms of pain that are not "useful". This understanding led Melzack to assert that pain is in the brain.

Awesome stuff!

Study group discussion: Type 2 polyglandular syndrome

Came across a new question today. Let me ask you guys -

So what is Type II polyglandular autoimmune syndrome?

Schmidt syndrome?

Yes, also known as Schmidt syndrome.

What are the components?

Adrenal insufficiency (Addisons)

Hypothyroidism (hashimoto)

Also gonadal insufficiency

And ?

Abs pancreatic insufficiency!

Yeah, Type 1 DM.

Good job!

Study group discussion: Vitamins (Antioxidants, Vitamin E and vitamins in egg)

Name the vitamins which are anti-oxidants?

Vitamin A, C, E.

Mnemonic: Ace the oxidants!

Which is the anti-oxidant important to prevent lipid peroxidation?

Vitamin E

Study group discussion: Tissues that are exclusively dependent on glucose for metabolism

Which things in our body are exclusively dependent in glucose for energy?

The lens.

Correct

Liver too?
Nope.
Brain?
No. It uses ketone bodies too!
Muscle?
No.

Cornea?

Cornea correct!

Heart.
Heart, no.
Interesting: Heart can use lactate.

Sperm
No. Sperm uses fructose!

It's RBC!
Oh ya. They are exclusively dependent on glucose! RBC can't metabolize anything else!

Study group discussion: Mechanism of hypercoagulability in obesity and smoking

How does smoking and obesity promote hypercoagulability?

Smoking increases reactive oxygen species. ROS reacts with LDLs causing increasing oxidized LDL, when deposited in intima becomes atherosclerotic plaques. Also ROS causes endothelial damage itself, increasing its permability to LDL.
Atherosclerotic plaques can rupture, exposing tissue factor. Or the plaque itself causes turbulent blood flow, increasing chance of thrombosis.

Nicotine causes vasculitis and thus causes turbulence of bood flow!

And obesity?

The various mechanisms by which obesity may cause thrombosis include: the actions of so-called adipocytokines from adipose tissue, e.g. leptin and adiponectin; increased activity of the coagulation cascade and decreased activity of the fibrinolytic cascade; increased inflammation; increased oxidative stress and endothelial dysfunction; and disturbances of lipids and glucose tolerance in association with the metabolic syndrome.
Source: Obesity and Thrombosis — ScienceDirect - http://www.sciencedirect.com/science/article/pii/S107858840600579X