GPHR-7060-02Sp20

05 - Incretins + Diabetes (Endocrine Module)

02-01-2020, Incretin (Endocrine Module)

What is appreciated about the Pharmacology Department at the esteemed Tulane University is that every day is another opportunity to stimulate the brain and learn something new. Incretins was a new topic to encounter.  Initially encountered from the Gastrointestinal module, the blocking of incretin was the mechanism of Natalizumb with notable side effects.  These proteins also play a role in the pathology of diabetes mellitus.

The negative feedback allows the human to slow down on consumption of food.  The endocrine system signals that the body is full. Being full signals the internal anabolism of glycogen and the building of the alpha 1,6 bonds and alpha 1,4 glycosidic acetal linkages being built. Too much, then the acetyl-CoA will shift its direction to the synthesis of malonyl Coa. The   biomarkers of Glucagon Like Peptide and Gastric Inhibitory Peptides signal the presence of food consumption.

The pancreas, derived from the endoderm,  produces the hormone insulin and amylin.  As reviewed from cellular biology, the ending “-in” hint that the receptors are located on the cellular exterior. The L cells from the gastrointestinal organs secrete GLP-1. The pancreatic response of insulin synthesis are part of the endocrine regulation that healthy patients take for granted.  This critical pathway deviates from its intended prototypes for those with diabetes mellitus.

The gastrointestinal assist the hormonal response with the release of the GLP-1 and the body possesses versatility with its multiple pathways of metabolism shown with multiple arrows in biochemistry textbooks.  The hepatic enzyme dipeptidyl peptidase-4 DPP-4 breaks down GLP-1.  The body is not supposed to store protein, which the former instructor Dr. R. emphasized.  Humans can analogize storage of carbohydrates and fats.  It is not meant to store nonfunctional protein or enzymes that are not needed.  The approach to protein is “We don’t make it til you order.”

Sitagliptin is a DPP-4 inhibitor, allowing the presence of GLP-1 to survive longer than its intended half life. Exenatide (Byetta ®) and Liraglutide (Victoza ®) are GLP-1 agonists.  These drugs have been noted for efficiency aids for weight loss.

The altered incretin response has been noted for its correlation to diabetes.  The normal response is show higher insulin response to oral versus intravenous applications of glucose.  However, the responses do not show the same level of disparity among diabetic patients.  Remember that incretin is the GI response to the postprandial state.  The missing biomarker of low incretin response also confirms the pathology of Diabetes.  The text PW notes that the reason for the insufficient incretin response is because of the pancreatic deficiency of properly response due to constant glycemic state.

Although the public simplifies diabetes mellitus simple as a high sugar disease, diabetes mellitus should also be considered as a protein misfolding disease, similar to what has been observed in the clinical indications of prions, Alzheimer’s, and Parkinson’s.  Amyloid proteins have been observed in model organism in studies simulating the hyperglycemic state.  The misfolded protein is completely useless due to the loss of tertiary and quaternary structures.  The three-dimensional spatial structure is critical for any protein to perform its function.  Correcting the misfolded protein will be considered a pharmacological target, thanks to the novel cost-efficient techniques with their potential to rapidly and efficiently manufacture antibodies not from the mainstay hamster ovary cells but from cheaper materials such as the E.Coli bacteria and yeast cells.

Extra Credit: Who were the researchers credited with this technology of protein refolding which has the potential for significantly decreasing the costs of cancer treatments?

Word Count: 700+ words    

05-2020 The fable of Helicobacter pylori + GI Module

Treating patients who have endured trauma will require expertise of the gastrointestinal system.  The GI has a mind of its mind that is prone to effects of stress and environmental hostility.  Therefore, the private sector with corporations like Dannon vest efforts to learn more about the microflora and identify specific targets to address the physiological effects of the enteric nervous system.  The discovery of H. Pylori proved to be a game changer.  Before the discovery, the physiological reactions were blamed on stress and spicy food.  Proper biomarkers have been identified to dismantle that long held mistaken belief.  

H Pylori

Since the curriculum makes room for science history, one can appreciate how far we’ve come and also resent for the regrettable mistaken beliefs and also a chance to marvel at the ridiculous beliefs  and general human idiocy, and its misconceptions that people have held as holy and above criticism, then maintained by those in power.  Mistaken beliefs have real consequences.

Memory:  The story of H. Pylori was told from a previous instructor of a cautionary tale for those who wanted to pursue science: you need more than book smarts and research prowess.  

The reading material for the GI Module included an article of its discovery, a game changer.  Before the discovery of the pathogen, it was considered a psychosomatic disorder of overly bossy mothers, implying that the proper role of the woman in the household as passive conformity. The renegade microbiologist “far from the medical mainstream” Robert Koch discovered the cause of tuberculosis. His nonviolent resistance to the mainstream paid off since we are all beneficiaries of his indefatigable pursuit.   The difficult isolation of the H Pylori thwarted Koch.    The featured excerpt from 1967 blames the “psychogenic symptoms” on role strain and role conflict in the family home and the particular failure of the woman to act as the docile nurturer.  

The isolation of the bacteria was difficult because it was present in individuals with no history of gastric inflammation.  Dr. Marshall volunteered as the model organism.  He infected himself and experienced gastritis.  But he had no ulcer.  Correlation of ulcer and the pathogen was concluded from epidemiology.

Patients were not recruited.  Samples from blood banks were analyzed.  The vector of transmission was through saliva.  The term “submerging” was used to correlate the prevalence of the diseases to socioeconomic determinants.

Poor hygiene, living in slums, and unsanitary conditions heighten the risk of infection.  The bacteria has two advantages of escaping detection: its special flagellate that allows it to swim and anchor itself to your bottom stomach lining.  Then, it establishes a comfortable residence in your acidic stomach by synthesizing the enzyme urease.  The products are carbon dioxide and ammonia, which is used to offset the hydrochloric acid in your stomach.  

What was unclear from the article was the presentation of the term “Lewis antigen” and the suggestion that individuals with certain blood types are more susceptible to the bacteria.  

“The Lewis antigen system is a human blood group system. It is based upon two genes on chromosome 19: FUT3, or Lewis gene; and FUT2, or Secretor gene. Both genes are expressed in glandular epithelia. FUT2 has a dominant allele which codes for an enzyme and a recessive allele which does not produce a functional enzyme. Wikipedia”

The article ends on an optimistic note for the aspiring scholar “to challenge accepted theories [...] with great benefit to society and science.”

True, if only one can survive being ridiculed as “weird” or “deviant” by the establishment that demands uniformity with the masses.  

“Discovery consists of seeing what everybody has seen and thinking what nobody has thought” Albert Szent-Györgyi was quoted.  

*

 GPHR-7060  uses a “Self-Directed Learning (SDL)” mode.  The text also reiterated the social ostracism that Dr. Marshall endured in the discussion of stress effects on the gastrointestinal system.  He failed to conform.  All he had to do was to look at his peers and act like how they acted.   The world of Science needs to maintain a collegial environment.   His superiors just noticed a disruptive pattern of behavior.  So they laughed, mocked, and jeered at Dr. Warren and Dr. Marshall.

*

The Washington Post also reported on another nonconformist, Dr. Li.  Thankfully, the government shut him down.  The Republic needs to maintain a collegial environment.  All Dr. Li had to do was to look around his peers and act like how they were acting.  Instead, he was too disruptive.  This was not to be tolerated.  

Word Count: 300+

05- Environmental Signaling 250+ words

Questioning a Cherished Ritual

The class had a provocative discussion.  Usually the majority holds a singular view.  However, the discussion  was unusually balanced, thoughtful and respectful.

How could we have known?

There were signs that the public health enforcement was very weak.  One quick glance at the figures made sure of it.  A walk (not a drive in your temperature controlled vehicle) down Elks Place revealed numerous businesses in violation of the city ordinance.  One could infer a couple things:  the health department is understaffed.

For the privileged who live in houses (and not multi-unit apartments) and drive cars (and not have to take public transportation), it may not have been noticed that the poor of New Orleans were living in great constraints.  They did not have resources.  The gulf between the middle class and the low income was noticeable.  The ignorance of the privileged about how the have-not caste members struggled was hurtful and disappointing.  Other signs portending disaster included: subprime quality of care, poor comprehension of cultural diversity in the United States, poor consumer protection, inadequate understanding of federal and state civil codes, delayed rolling out of Medicaid, inadequate infrastructure, lagging public policy.  In order to prolong health inequality, it is essential to have individuals in power who proclaim that there is no problem and everything is fine, and also persecute those who challenge the gospel that "everything is fine."  The ecosystem of New Orleans is an example of a perplexing irony: how is it possible to have a world-class medical school and a public health school and yet have the environment remain toxic, violating numerous health guidelines. 

"We just expanded Medicaid last year [2018]," said Dr. A, a family medicine physician who serves at a clinic identified as a Federally Qualified Health Center in New Orleans. Why did it take so long?  How?  As if still operating a pro-slavery separatist Confederate state, the defiance of the state of Louisiana in complying with federal statues, the disrespect to the United States of America, and the failure to serve the American people should not be tolerated anymore.  

The revaluation of a cherished custom requires serious compassion and generosity.  Outsiders may have found the university actions of revering the annual custom to be bewildering.  TV monitors on the 4th floor next to the Tulane Physiology Department displayed shuttle schedules to get to the parades.  The BMS Student Association emailed the same shuttle schedules.  Resources were used to get gatherings that offered plastic beads with an amassed value, when compared to the North Korean won elevates the latter to the status of the Swiss franc.  But the same resources were not used to help students to get to community service sites.   

The federal government did not provide the warning about the Covid until after Mardi Gras. Governor Edwards did receive a briefing about the dangers of the Coronavirus in February, in time to cancel the annual celebration that generates tourist revenue.  After the lockdown, news reported that Planned Parenthood clinics were threatened to shut down, even though they provide timely care for women.  

True. However, the federal government is known to act slow. However,  it is not allowed to interfere in the affairs of the state.  The onus was on the Governor who is supposed to bolster the health department and ensure that the state is prepared for such emergencies.  To echo Benjamin Franklin, "If you fail to plan, you are planning to fail! "  

The tragedy of the Covid occurred long before Mardi Gras and the warning signs were there.  Poor infrastructure was one of the many problems.  All pediatric providers should warn the caretakers of children that this ceremony is not meant for children.  It is not safe.  

Furthermore, the lack of conformity to the guidelines provided by the Centers for Disease Control   was one of the second warnings that no one should take the risk to attend Mardi Gras, especially if you are not a rich, white male.

Dr. M emphasized the importance of going outside and getting some sunshine.  An alternative is to consume vitamin D supplements and use a manual treadmill.  Going outside is not a safe option for Asian Americans who may confront aggressors of an uneducated populace scapegoating them for the Coronavirus.  It is about as useful as talking down a patient in the ER who is presenting rotary nystagmus.

The first fatality in Louisiana was a tourist visiting from Ohio to attend Mardi Gras.  His steps should have been traced so that individuals can know if they are possible asymptomatic carriers who continue to infect others unknowingly.  But testing has been prioritized for those who show respiratory symptoms.  Furthermore,   the workers who had picked up the trash after Mardi Gras deserve more than sympathy.  Those trash must have functioned as bioweapons, carrying remnants of the Covid virus.  The working poor had no choice but to undertake risky, dangerous jobs.  This was the same quandary that Dr. Alice Hamilton observed; she advocated for safer working conditions that formed the basis of OSHA.

*

The benign title of the course is about how leaders in healthcare can be mindful of the factors outside of the exam room.  Dr. M explained of his work and his demonstration of resilience and professionalism throughout what should not have been a controversy: the pursuit of safety for children.  His opponents included the petroleum industry and also his employer.  Dr. AK. explained the basics of chemical treatment used to treat water.

For those new to Tulane University, the university announcements on boil advisory notices can be bewildering.  When those notices are received, you have to get bottled water, increasing your exposure to BPA.  

  After class, I watched the Nova episode on what happened at Flint, Michigan and the residents there were poisoned by lead, because those in power wanted to save money.  The manifest function was a telling of how cutting corners on a vital part of epidemiology.  The latent function was demonstrating what professionalism is about when pursuing justice.  Even with truth on your side, your opponents will malign you. First, they dismiss the findings.  Then, they demean your character.  As mentioned in a previous post, historically, the (toxic) masses have been impatient and intent on persecution based on rumors and falsehoods. When a lone EPA official spoke up about the injustice of the improper handling of water, his  colleagues and superiors refused to support him, inciting that the pursuit of justice can be a lonely affair that can test your equanimity.  Unlike winning NIH grants, there is no glory for helping poor, vulnerable people. Speaking up is a disruptive activity and must be punished. 

"Disruptive" “those are words that white people use to express our racial fears.” Chana Joffe-Walt

Dr. Sapolsky mentioned this quote used in the text for Endocrine Pharmacology.  For progressive reformers who envision a better present and future, the slander used by those around you and worse, the apathy, can be frustrating and stressful.

April Community Service - United Way HandsOn Virtual Volunteers: Phone a Senior Program

April  Community Service

Hours: 1.33

Cumulative: 27.61

Word Count: 351+

United Way HandsOn

Virtual Volunteers: Phone a Senior Program

Two clients were assigned.  My duty was to make phone calls twice a week to confirm the food delivery.  The food delivery was expected to occur every Monday and Thursday.  I corrected their home addresses and confirmed the best phone number for the delivery person to make contact.  I counted how many people were in the household.  

HandsOn New Orleans had coordinated the “Serve our Senior” meal delivery. The effort was a partnership of the Mayor's Office, HandsOn New Orleans, and the World Central Kitchen.  The World Central Kitchen is a non-profit organization led by a professional chef and an advisory board that includes judges from the Food Network show “Chopped.” 

The initial phone call took the longest because the database input info was incorrect.  I had to enter the correct address. During each follow up, I had to make sure that there was no problem.  Then, the info was entered into an online database.  The meal delivery service  were made fresh on the days of delivery.  Underserved members of community often experience food insecurity.  I made sure to note any special needs such as any mobility restrictions.  During the follow up, the clients raved about the food and thanked the service. 

Ms. J was quick to share about her needs for sanitary supplies like toilet paper.  I was advised to direct these requests to 211. Then, she referred me to clients who could also use the service.    

Mr. S was a little difficult to reach.  He did not have a mobile phone or a phone equipped with voicemail or text, because he explained that his Lifeline account got cancelled. He explained how he had to get a new wheelchair and because of the unexpected medical expense, he was not able to spend as much for food.  

Each volunteer hour was valued at $25.44 an hour according to federal guidelines.  Each hour was going to be used as FEMA reimbursement  to the City of New Orleans.  Hopefully with the additional reimbursement, the City of New Orleans can conform to the recommended guidelines issued by the CDC and fix housing and improve public transportation. 

Dr. Vivek Murthy had warned about social isolation and how it led to poorer prognosis. 

The Pandemic & Innovation

Why didn’t we have this sooner?

Interventions addressing health disparities and food insecurity should have been addressed sooner and with greater urgency.  It took a pandemic to dismantle apathy and to initiate action. 

The Pandemic is also an opportune time for demagogues to truncate the protections of the most vulnerable.  

District of Columbia v. U.S. Department of Agriculture (U.S. District Court - District of Columbia, March 13, 2020): The federal district court issued a nationwide preliminary injunction halting a federal rule that would remove an estimated 700,000 individuals from the Supplemental Nutrition Assistance Program (SNAP). Read the abstract here. The Network for Public Health Law 

The President is working on limiting the distribution of food stamps, which primarily benefits poor children whose only fault is that they were born to poor families.  

Providers who are not familiar with the socioeconomic determinants of health will say the same advice: Exercise more.  Consume fewer calories and salt.

If your patient lives in fear of housing or financial insecurty, the provider's advice on wellness will get translated as "Blah blah blah."  If your patient is poor, your patient probably cannot afford quality food or the time to make the food (go to the grocery store, stand in line, haul the groceries, wash the vegetables, chop the vegetables, cook, wash the dishes and cooking utensils, take out the garbage, store the leftovers). Why go through all that after a tiring day of work when you can quiet the stomach rumblings at Ick-Fill-Eh?  Too late. Your limbic system overrode the wiser prefrontal cortex and there you are now, waiting in line, selecting your dipping sauce.  Your patient can live in a neighborhood that does not permit safe walking routes.  

United Way HandsOn

Virtual Volunteers: Phone a Senior Program

  Fri 4/24/2020 11:16 AM

 World Central Kitchen  

 

https://council.nola.gov/news/march-2020/councilmember-kristin-palmer-and-partners-to-offer/

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Description:

If you are elderly or know someone in need of delivery, please contact Connie Uddo at connie [at] nolatreeproject.org https://twitter.com/NolaTreeProject

Anti-Asian Coronavirus Scapegoating has infected the Tulane downtown area

Tulane University Police Department                         
Downtown District
DATE & TIME OF OCCURRENCE:   Tuesday April 7,2020 at about 6:30 PM
LOCATION:   Intersection of N. Claiborne Ave. and Tulane Ave.

REPORTED OFFENSE:    At or about 6:40 PM, two Tulane affiliates were walking on Tulane Avenue near N. Claiborne Avenue. They were confronted by an unknown male who asked if they were Chinese, then asked if they were Chinese or Japanese, saying, “If you are Chinese or Japanese, I’m going to kill you.” The subject then lifted his shirt and showed the affiliates a handgun in his waistband. The affiliates continued walking with the subject following and again asking the same question. One affiliate then told the subject they were “here to help” and work at the hospital. At this the subject said, “Oh, you’re here to help.” The subject then held out his fist and bumped it against the affiliate’s, turned and walked away.

SUSPECT’S DESCRIPTION:   Black male, 20-30 years of age, 6’ tall with a slim build.  Wearing a red or orange colored T-Shirt and blue jeans.
INVESTIGATION ONGOING:If you have any information about these crimes, call TUPD at 504-865-5381 or NOPD at 504-821-2222.
*Descriptions provided by victim/witness. Information about the race or ethnicity of alleged offenders is provided only to aid detailed descriptions that include physical stature, clothing or unusual characteristics. Racial descriptions do not, by themselves, offer a meaningful picture of an individual's appearance.

Search Results

Web results

FBI warns of potential surge in hate crimes against Asian 

Violence because of Skin Color: Attacking Americans who are not Chinese.  Slide from Dr. Stephen Chao

Most aggressors  may not be aware of how much harm they are causing.  Bystanders can   help.  These days, Asian Americans are being targeted and being blamed for the Coronavirus.  And this is an opportunity for everyone to engage with  non-violence - to do something, rather than nothing.  These types of aggression range from "mild" harassment to physical violence -- all of which are unacceptable.  Many people are so stressed about the pandemic that they are taking it out on others.  Since social isolation, a lot of us have realized "We are all in this together."  We should help each other.  When one group is being unfairly targeted, we should use this opportunity to advocate for peace.

The Director encouraged the students to keep journals of life under the pandemic.  It would be nice if the blogs of the previous cohort who had experienced Hurricane Katrina and took classes at Baylor University were made available. It can be tiring to constantly affirm that everything is fine on the Zoom webcam.  Professionalism dictates putting your best face forward. It's the American custom to say you are fine even when the situation is not.  

Now, there are two pandemics to confront. 
Two pandemics that need flattening of the curve. 
Both situations require PPE. The CDC now recommends masks.  If you look Asian, it may not be wise to go outside. There’s nothing wrong with ordering dry pasta and dry beans from Target or Walmart to be delivered to you.  But if you must, additional PPE such as bleaching your hair blond, wearing sunglasses, and wearing your Halloween and Mardi Gras masks may be recommended.  

Report: Sam’s Club stabbing suspect thought family was ‘Chinese infecting people with coronavirus’

Reading of the two pandemics fuels anxiety, the primordial kind seen among babies: when one baby cries, the surrounding peers also cry.  

Fears of the Coronavirus can turn to psychomimetic rage.  Just as it is not advisable to talk down a patient presenting rotary nystagmus, alternatives to achieve deescalation should be learned. 

https://www.facebook.com/ihollaback

Cell Control GPHR-7050-01Sp20

The Life-Preserving Advance Directive of Planned Death - Apoptosis  

Short Version:  Calcium and apoptosis are important.

Long Version:

The entrance of calcium is linked to multiple events:deleterious and beneficial to cellular regulation.

Supplementary Material on the background:

The hallmark of the phosphatidylserine flipping to the extracellular side of the membrane is a sign of apoptosis, a controlled process that costs ATP.  On the extracellular side are phosphatidylcholine and sphingomyelin.  The choline is the more abundant lipid.  When the serine flips to the extracellular side, it is time for the macrophages to arrive and vacuum the clutter.

The border  has a variety of checkpoints for drugs.  The first is the blood-brain barrier: ATP Bind Cassette.  It is comparable to the current US-Mexico border.  Under the Trump Administration “Remain in Mexico” policy, refugees who are running away from gang violence, starvation, military juntas, narco gangs, sexual assault are finding it very difficult to enter to claim desperate amnesty status.  Changes in the voltage of the neuronal membrane can get detected using the localization measurements such as the use of voltage sensitive dyes.

Organs derived from endoderm such as kidney and liver also utilize the  ATP Binding Cassette.  The liver uses the ATP for Pre systemic Drug Clearance and the kidney can excrete using the same expensive mechanism.

Calcium is a critical transport process such as VMAT (vesicular monoamine transport).  When the vesicle docks at the membrane, calcium enters.  The cell conducts an exocytosis using cellular UPS packages wrapped in claritin residues.  The ending endocytosis allows recovery of the package materials.

The hepatic presystemic clearance has destinations to the lumen of the gastrointestinal tract or to the portal vein.

Cytochrome c is located in the matrix of the mitochondria positioned between cytochrome c reduce (Complex 3) and the oxidase (Complex 4).  When the energy carrier NADH enters, protons are pumped to the intermembrane space making the space more acidic.  When the cytochrome c (cyt c ) moves to the low-calcium cytosol, it is time for apoptosis, or decluttering.

Lamin is a protein that is located on the interior side of the nuclear envelope.  When the MPF phosphorylates the lamin, it is the prometaphase in which the old nuclear skin is shedded.  Lamin is also the in vivo substrate of effector caspases.

Extrinsic Apoptosis:

When the Fas ligand or the killer lymphocyte wants to start extrinsic apoptosis, a protein sandwich known as the DISC is constructed.  Death Domain is located on Tumor Necrosis Factor Receptor.  Despite the term necrosis in the name, this is the player of extrinsic apoptosis. Fas Associated Death Domain is located on MOMP, or Adapter protein.

Bax can then folds into a donut with flowery petals  to allow the hydrophilic cyt c to pass from the matrix to the cytosol.  It is like Moses, parting the cellular debris, followed by the  musical rendition "Let my Cytochrome Go."  Following the cyt c retinue is the Apaf 1 (Apoptosome) and apoptosis inducing factor Smac/Diablo.

The use of Actinomycin can interfere with the release of the cyt c, blocking the path to intrinsic apoptosis.

The dumpsters of the eukaryotic cell are located in the lysosomes. Lysosomes maintain the V class ATPase.  The product is the proton gradient, which is necessary to activate the proenzymes.  Not just a  dumpster, lysosomes also act as a storage facility to store a variety of hydrolases.  They are inactive until the acidic environment cleaves the zymogens.  V class pumps are the converse of the F pump, which are located in plasma membranes, mitochrone, and thylakoid membranes.

Uncoupling Protein can interfere with Calcium Regulation.  Fewer ATP is produced.  ATP is needed for the excretion of calcium ions in order to maintain a low calcium environment in the cytosol.  ATP is needed for the calcium pumps in the eukaryotic plasma membranes the on the membranes of sarcoplasmic reticulum of muscle cells

Drug design must target the ATP Bind Cassette, a checkpoint that requires ATP bribing at the blood-barrier border. Compared to extrinsic apoptosis, intrinsic apoptosis was described as a more minimalist process.  No DISC sandwich required.  Then again, apoptosome can be described as the burrito of intrinsic apoptosis with ingredients like Apaf and Smac/Diablo.

Like an accredited organism, at the top of the hierarchy are the BHC-only factors like Bad and Bim.  When caspase 8 is activated for the intention of extrinsic apoptosis, caspase 8 can cleave the Asp D site of Bid.  Then, MOMP becomes activated.  Bid is considered “strongly apoptotic” and can initiate processes like reorganization of the mitochondrial cristae.  Question:  Does the surface area increase?  

The DISC burger has layers of DED, FADD, and DD.  DED is found on Pro Caspase 8.  FADD is located on the Adaptor protein.  

MPM (mitochondrial outer membrane permeabilization) drills a hole in the mitochondrial outer membrane and cleaves Bid, the initiator of apoptosis.

https://www.drawittoknowit.com/course/pathology/glossary/immunology-microbiology/adaptive-immunity-humoral-response?source=course&source-glossary=physiology

Question:  What are the lab techniques to detect organelle dilatation and ribosomal disaggregation?  These cellular hallmarks are part of the reversible phase of necrosis.  The cell can develop  pimples, known as blebbing, not to be confused with the term “blob.”  The surface area increases.  Furthermore, because of its unfortunate resemblance to the informal “blob,” blebbing may get confused as a simple process.  Further, there is  a protrusion of the membrane.  Spikes made microtubules form, compromising the asymmetry of the membrane.  Fragmentation occurs and outgoing cellular UPS packages are mailed out in apoptotic vesicles. Question: Is this process different from opsonization?

"

Opsonization 

is the coating of a particle with proteins that facilitate phagocytosis of the particle by tissue macrophages and activated follicular dendritic cells (FDCs) as well as binding by receptors on peripheral blood cells" ScienceDirect

Much of the changes that mark necrosis point toward the increase of entropy. Apoptosis is marked with terms like “fragmentation” and lowering of entropy.  The cell condenses under low entropy.  Mitochondria becomes smaller during apoptosis because of the flowery pore made by Bax.  However, the mitochondria will swell during necrosis because there are no flowery pores and Bax has no role during necrosis.

Changes that portend higher entropy such as the “rupture” of the membrane and the “dispersal” of organelles mark the reversible phase of necrosis.  There are no neatly packaged clathrin UPS packages for the cell to pick at a later time.  The lysosomes, the cellular dumpsters and storage facility of proteases powered by V class ATPase, are destroyed.  Neutrophils , the special white blood cells that are the first responders to bacterial infections, arrive.  Inflammation occurs.

Plasmolysis is described as “hydrolytic fusion of cytoplasm” which seems like a strange contradiction.  Hydrolysis occurs, which results in the removal of water molecules.  This is a breakage of bonds.  Then, there is a fusion of the dehydrated products.

The Fas ligand can bind to the CD95, the cytoplasmic tails of Fas or to the DISC burger. Uncontrolled  influx of calcium can be toxic.  It can cause irreversible cellular damage.  Luckily, the calcium detectors know to initiate apoptosis by calling the BH3 initiators.

Pharmacology Review:

The cardiovascular module was then reviewed.  Delayed after Depolarization is the pathology when the sodium calcium exchange is disrupted.  The cytosol where the caspases reside require a low calcium environment.  Therefore, excess calcium must be pumped out.  A currency exchange permits the exchange of three sodium ions from the extracellular for the excretion of one calcium ion.  Sodium is responsible for the rising phase of action potentials.  The plateau phase is the work of the calcium ions. The presence can get detected with measurements using GCAMP.  Calcium ions will bind to the calmodulin, resulting in bright fluorescence.  When the levels of calcium ions are low, the fluorescence will be dim. When the catecholamines are stimulated, there will be an excess of intracellular calcium.  The sodium calcium currency must be exchanged to prevent the Delayed after Depolarization.  Furosemide works by blocking the sodium potassium chloride cotransport in the thick ascending loop of Henle by binding to chloride transport ion channels.

Ion channels allow a wormhole for the charged particles to bypass the hydrophobic membrane.  They are not like transporters that span the entire depth of the membrane.  Digoxin covalently inhibits the primary sodium potassium transport.  This results in increase of cardiac calcium and increases the force of heart contraction. Because the intracellular calcium can get excessive, Digoxin can cause arrhythmia.  If the mass of the heart remains constant, then the acceleration must increase in order to accommodate the increase in force. Like Digoxin, spironolactone blocks the primary transport but targets the distal convoluted tubule, which is farther from the Bowman’s capsule and the Loop of Henle. Finally, Amiodarone is the rhythm control medication that can block the potassium current and its side effects include QTc prolongation, EAD, and Torsade.

To prepare for the exam, physiology was reviewed. The SGLT2 transporter is found in the kidney proximal tubule, close to the glomerulus where ninety-percent of glucose is recovered.

Physiological stimuli include hormones and growth factors, boh are signaling factors.  As Dr. M mentioned, low dihydrotestosterone (DHT) is a signal to start apoptosis.

Normoxia  will result in proteasome degradation of HIF. Under hypoxia, chromatin change will get observed (Question:  How is this change observed?  GFP?)  Lysine demtheylase are genes that assist with the pathway toward apoptosis.  Unfortunately, one of the effects of apoptosis is ROS because of the extrusion of GSH, which converts hydrogen peroxide into water.

Mitochondria plays a role in calcium regulation and synthesis of steroid hormones in organs like the adrenal cortex.  Cholesterol, however, is synthesis in the low calcium environment cytosol.

Question:  How does the hormone aldosterone cause fluid volume to increase by the mechanism of reabsorption sodium?  The movement of Calcium and Phosphate ions occur together because they are “buddies” (Khan Academy).  Is there a similar friendship between sodium and water?  Sodium is considered a highly soluble ion and will not precipitate.  It is a known spectator ion for many reactions.

Phosphatidylcholine - Wikipedia

Phosphatidylserine - Wikipedia

       

Question: Is NMR used to detect the presence of phosphatidyl serine when it flips to the external surface and crowds out the phosphatidylcholine and the sphingosine?  Choline is marked with the positively charged ammonia that is sterically hindered by three methyl groups.  The serine group can be detected if the NMR can detect the hydroxyl group.

Question:  Where do the myelin figments come from?  What is the source of those apoptotic myelin figments?

 The content for the second exam requires proficiency of pathology, histology and immunology.  All the modules are curated to potentiate previously learned knowledge. Some of the details will have to be refreshed to further potentiate.