Discuss the possible reason for the difference between the BGG and BSA standard curves

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Assignment deadline: 16th December 2020. This assignment is marked as late submission and 15% will be capped.
You may find attached the documents that will explain the procedures to do the Bradford Assay
The write up:
1,000 words (+/- 10%) Materials and methods do not count towards word limit. Figure legends do not count towards word limit. Discuss (i) the possible reason for the difference between the BGG and BSA standard curves (ii) how this affects the accuracy of the ADH measurement, (iii) suggest a solution to mitigate this problem. Fulfktly referenced in Harvard style.

Write a brief 175- to 350-word summary that includes a description of the functions of the primary brain areas. Address how defects in these areas lead to expressed pathology.

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Respond to the following in a minimum of 175 words:

Why is it important to understand the intended processes of drug metabolism as a therapist?

Support your opinion by explaining the for reasoning it, include the reference you’re drawing upon to inform your reasoning. Remember to make your reference citations in APA format, and yes use of the text is fine as a reference.

(2) Assignment Content

Complete the Brain Structures and Functions Worksheets. Remember to do both sheets, one is a brain function diagram that you label the structures pointed to, the other is a worksheet that asked you describe the function of a particular structure and what happens if that part is damaged. Do not simply quote a definition of the structure, describe it in your own words.

Write a brief 175- to 350-word summary that includes a description of the functions of the primary brain areas. Address how defects in these areas lead to expressed pathology.

Format your summary consistent with APA guidelines. Within your answers, please list the references used for each question, rather than at the end, there is no need for a separate reference page.

Submit your assignment.

(3) Assignment Content

Write a brief 350- to 700-word paper that includes the following:
– Describe the differences between pharmacodynamics and pharmacokinetics.
– Describe an example of pharmacodynamics.
– Describe an example of pharmacokinetics.

Include a minimum of two sources. Be sure that you use appropriate (that means peer reviewed) references.

Format your paper consistent with APA guidelines.

Summarize why you have selected this experience as one of your most meaningful.

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Summarize why you have selected this experience as one of your most meaningful. In your remarks, you might consider the transformative nature of the experience: the impact you made while engaging in the experience and the personal growth you experienced a

Provide and analyze an example from Chapter 1 of a success and an example of an ongoing problem in the history of disease that, together, illustrate how the history of disease can be seen from these two completely different viewpoints.

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Write a 400- to 500-word essay in response to the following:
“The war between disease and doctors fought out on the battleground of the flesh has a beginning and a middle but no end. The history of medicine, in other words, is far from a simple tale of triumphant progress.” This quote from p. 1 of Blood and Guts encapsulates the main point of the first chapter. Provide and analyze an example from Chapter 1 of a success and an example of an ongoing problem in the history of disease that, together, illustrate how the history of disease can be seen from these two completely different viewpoints.

What are the key components of strategic planning for hospitals and healthcare systems?

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In this coursework assignment, you will be answering to two question prompts. You will write a 1 paragraph response to each of the question prompts. In total, you will be writing two paragraphs. These two paragraphs combined must be AT LEAST 1 full page (not including cover and reference page).
———-Begin Question Prompts———-
Paragraph #1 Prompt: Using the video presentation as a high-level summary, what are the key components of strategic planning for hospitals and healthcare systems?
***See file attached, titled, “Reading Materials” for video information and link.***
Paragraph #2 Prompt: Describe the various aspects of SWOT (strenghts, weaknesses, opportunities, threats) analysis. How would you apply its use within a healthcare management system?
———-End Question Prompts———–
Additional Important Instructions:
-Your response to the two question prompts MUST be based on the reading materials from the attached file, titled, “Reading Materials.”
-You must reference AT LEAST one of the “reading materials” for each of your paragraphs. (This means you will have to use at least 2 of the references listed on the attached file, titled, “Reading Materials.”)
-Please make sure you are citing your references, both in-text and on the reference page, per APA guidelines.
-Please make sure you are answering ALL PARTS of each of the question prompts in its entirety! Do not leave any parts unanswered!
-Please make sure your responses are very detailed. Plus, make sure you explain your answers well, concise, and clear!

explore the impact of neuropathy on wound healing.

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Despite the best efforts of clinicians involved in wound care, diabetic ulcers can be hard to resolve. The slow healing of a diabetic ulcer may be due to several factors including peripheral vascular disease, neuropathy and the presence of infection. Diabetic neuropathy impacts on a wound in many ways, for example leading to overloading of the area, affecting normal wound healing processes such as angiogenesis and affecting the immune cells locally. This essay will consider the potential impact of diabetic neuropathy on healing in a patient with a foot ulcer. The role of the neuropeptide Substance P will be included. The essay will include a critique of a research article (Krishana et al, 2007) supporting this topic area.
You will be required to submit a 2800-word assignment and this work should include:

1. A brief introduction

You will need to outline the relevance of the topic area. This should NOT be in terms of figures that mean little to the general reader but should demonstrate an understanding of why this topic is important to those managing the patient.
You need to define the scope of the essay. The basic pathology of diabetes is NOT required (as it is assumed that you know the pathology of diabetes) but should focus on factors related to the development of wounds so that the introduction quickly leads on to become very specific to neuropathy. The introduction needs to identify what is included in the essay and why.

2. Main body of the first part of the essay

In the main part of this essay, you are expected to explore the impact of neuropathy on wound healing. You might give a brief overview as to why neuropathy develops in diabetes and you might consider how sensory / motor / autonomic neuropathy causes an ulcer. But remember, the focus of the essay is not about causing an ulcer, it should be moving your knowledge on to how the neuropathy prevents the ulcer from healing. The essay needs to include factors that are not simply about the ulcer not healing due to the causative factors remaining, it should be about how the neuropathy changes the process (the normal physiology) of wound healing. There are several neuropeptides involved but in this essay, you should only provide greater detail on Substance P.

You will need to show good academic writing skills to present the work fluently, showing the depth of information and the ability to link concepts. You need to be explaining clearly the pathology to a level that describes what is happening in tissues and cells. Any molecules/cells you describe need to be clearly explained and you should not assume the reader knows what the molecule/cell normally does. You should continually refer back to the main theme of the essay – the inability of the wound to heal.

You should use no more that twelve articles to support your work in this section. I have provided six articles that you should find useful and can include within those articles.

3. A critical exploration of the evidence.

One article has been provided (Krishnan et al, 2007) that has investigated whether the wound healing rate is related to neurovascular factors. You should write a critique of this paper.

4. A coherent conclusion

Your essay should finish with a summary of the key information given and perhaps a reflection about how the knowledge gained may impact on your management of a diabetic foot ulcer in your future practice.

What is the most likely reservoir for the causative organism in this case?

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Case Study 3

From The Microbe Files:  Cases in Microbiology for the Undergraduate.  Cowan, Marjorie Kelly. pp 49-50, 61  Benjamin Cummings 2002

You work in a small family practice in rural Virginia.  A man in his early 50s comes in with a complaint of intermittent fever (102-103°F) and headache for the past two weeks.  The physician examines him and takes a history.  The only clinical finding is a wound about the size of a quarter on his right thumb.  Axillary lymph nodes are swollen and tender.  The man says he cut himself while skinning a rabbit three days ago.  On the basis of these observations the physician prescribes streptomycin and asks the man to call if his symptoms don’t improve in three days.

The physician asks you to draw blood and tells the patient he should return in four weeks for another blood sample.  She says there is no need to culture the wound.

  1. On the basis of the limited information above, the physician has obviously made a diagnosis.  What is it?  What does it look like when Gram stained?
  2. What is the most likely reservoir for the causative organism in this case?
  3. Why draw blood twice?
  4. Why not culture the wound for the bacterium?
  5. What are some other common infections that humans acquire from animals? (These are also known as zoonoses).

The Usual Suspects

Common microorganisms causing infections in the cardiovascular system1,2,3

Bacteria3

Gram-positive

Bacillus anthracis, Clostridium perfringens, Streptococcus pyogenes, Other streptococci

Gram-negative

Bartonella henselae, Borrelia burgdorferi, Brucella species, Ehrlichia species, Francisella tularensis, Rickettsia species, Yersinia pestis

Fungi

Various

Viruses

Coxsackievirus, Dengue fever virus, Ebola virus, Epstein-Barr virus, Yellow fever virus, Human immunodeficiency virus

Protozoa

Babesia microti, Plasmodium species, Schistosoma species, Trypanosoma cruzi, Wucheria bancrofti

1Not all of the infections appear in this chapter.

2Not an exhaustive list.

3Many bacteria can cause bloodstream infections if given access; this table lists those adapted to cause disease in this system.

 

What is the difference between a ‘chemical’ and a ‘drug’?

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Lead Identification Phase in the Drug Discovery Process

Drug Discovery/Development Process

Basic Research

Discovery

Preclinical Development

Clinical Development

FDA Filing

Discovery Phase of Drug Development

Basic Research

Discovery

Preclinical Development

Target Identification

Target Validation

‘Hit’ Identification

Lead Series Generation

Lead Optimization

Safety Testing Before FIM

Currently Marketed Drug Targets

Current therapies are based on less than 500 molecular targets

Why Drugs Fail in the Clinic

Phase II failures 2008-2010

Lead optimization plays significant role in success of drugs

Efficacy Failures many times are “mechanism of action failures”

Discovery Phase of Drug Development

Target Identification

Target Validation

‘Hit’ Identification

Lead Series Generation

Safety Testing Before FIM

Lead Optimization

Start – with 1 million -Thousands- Tens -One/Two – Ending

Hit Identification Phase

High throughput screening of corporate deck to identify ‘Hits’.

  • Large corporate compound decks contain >1,000,000 compounds
  • Screen entire deck or carry out ‘focused’ subdeck screens depending on target
  • A hit is defined as a compound that exhibits a preselected level of activity against the target in the HTS assay
  • Each compound is tested in an assay for the target at single concentration (10 mM)

High throughput screening of corporate deck to identify ‘Hits’.

1536 well plates testing approximately 1500 test compounds per plate

Hit Identification Phase

Primary Hit:

Validated Hit:

Confirmed Hit:

  • Exhibit activity above threshold in primary screen at 10 mM
  • Exhibit activity in single point retest at 10 mM
  • Identity and purity of compound is confirmed
  • Compound shows a dose-dependent response CRC analysis
  • Compound shows little or no response in control assays
  • Ideal if related compounds in deck also show activity (not ‘singleton’) eg. >50% inhibition in a binding inhibition screen eg. Repeat at >50% inhibition in a binding inhibition screen
  • Optimal if compound shows activity in a ‘Secondary’ assay eg. Agonist shows activity in FLIPR and IP3 assay

Lead Series Identification

Hit Clusters:

  • From ‘Hits’, several ‘compound clusters’ may be identified by structure
  • Discovery team can select from these clusters to explore further
  • Analogues of the clusters can be chosen from corporate deck or for purchase for testing in primary assay
  • Medicinal chemists may begin to synthesize analogues based on hit structures -Compounds may be tested in single point or directly in CRC analysis – Single compound synthesis (1-5 compounds per round) – Parallel chemistry compound synthesis (10 – 500 compounds per round) – Typically a small group of chemists assigned to program to expand upon hits

Compound clusters expanded and explored to identify ‘Lead Series’

– Demonstrable and tractable Structure Activity Relationship (SAR) ‘Lead’ characteristics

– Demonstrable concentration-dependent activity at primary target

– Ease of synthesis. Chemically tractable scaffolds that are amenable to analogue generation

– Prior art has been searched, a clear intellectual property path has been identified and the competitive landscape is understood

– Minimal activity at primary off–target and/or SAR for off-target activity tractable Once several lead series are identified with tractable SAR

– Full complement of Medicinal Chemists is added and the project advances to full-program status

Goal of Lead Optimization Phase

– What are ‘drug-like’ properties ? Deliver a compound suitable for testing in Humans

– Multiple properties are required to be optimized for when working toward a clinical drug candidate?

– What is the difference between a ‘chemical’ and a ‘drug’?

“Drug-Like” Properties

“Drug-like” Properties

  • H20 Solubility
  • Lipophilicity (Log D)
  • Molecular Size
  • Acid/base Properties (pKa)

Goal of Lead Optimization Phase

Deliver a compound suitable for testing in Humans

– What are ‘drug-like’ properties ?

– What groups are involved in lead Optimization Phase ?

– Multiple properties are required to be optimized for when working toward a clinical drug candidate?

– What is the difference between a chemical and a ‘drug’

Discovery Project Team

  • Chemistry
  • Biology
  • PCO

Lead Optimization Phase

Optimizing Leads

  1. Pharmacological Potency and Mechanism of Action Optimization
  2. Physiochemical Optimization
  3. Cellular Optimization – Lipinski’s rule of 5

– Knowledge of drug target location

– Do properties of drug facilitate access of compound to target ?

  1. Pharmacokinetic Optimization

– Do properties of drug facilitate safe and timely delivery for optimal efficacy and safety ?

  1. Safety Optimization

-Minimize and understand on target (mechanism-based) and off-target unwanted activities in compound

– Decrease the amount of drug required to achieve therapeutic endpoint

– Understand mechanism of action of compounds Simultaneous multivariate in real time

 

 

 

 

Discuss what this means in the context of the functions of these two systems.

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The heart and lungs are heavily dependent on one another; without one, the other’s function will fail. Discuss what this means in the context of the functions of these two systems. Are there other examples of this within the human body?

Explain the primary reasons for these choices.

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Here are three properties that you would prioritize if you were running a lead optimization program. Explain the primary reasons for these choices.
1. Genotoxicity
2. Absorbation of compounds
3. Dose linearity and repeat dosing