Evodiamine Research Paper

Evodiamine Research Paper
Evodiamine is a bioactive compound present in the fruit of Evodia rutaecarpa (Juss.) Benth [1].
Initially, it was identified as a vanilloid receptor 1 (TRPV1) agonist, which possesses a property that
can be utilized to modulate pain [2]. Up to data, three proteins are believed to be direct targets of
evodiamine, including TRPV1, the aryl hydrocarbon receptor (AhR), and topoisomerases [3–5].
These proteins seem to be important in inflammation, cancer and other diseases. In fact, many other
pharmacological properties of evodiamine have been uncovered, such as the anti–tumour, anti–
microbial, and anti–inflammatory activities [6].
Previous studies found that evodiamine has the anti–obesity effects. The possible mechanisms were
proposed. Part of anti–obesity effects of evodiamine was thought to be enhancement of uncoupling
protein–1 (UCP1) thermogenesis through β3–adrenergic ... Show more content on Helpwriting.net
...
Several upstream kinases have been reported to activate AMPK, including liver kinase B 1 (LKB1)
[12]. LKB1 is predominately localized in the nucleus under normal physiological condition, and is
translocated to cytosol in response to stimulation, which leads to subsequent AMPK
phosphorylation and activation [13]. When activated, AMPK decreases fatty acid levels by
phosphorylating and thus inhibiting acetyl–CoA carboxylases (ACC), a critical enzyme for
controling fatty acid biosynthesis and oxidation [14]. The activation of AMPK also decreases total
cholesterol (TC) and triglyceride (TG) levels by inhibiting the activity of glycerol–3–phosphate
acyltransferase (GPAT) and HMG–CoA reductase, respectively [15]. AMPK has therefore been
proposed as a major therapeutic target for obesity and obesity–linked metabolic disorders such as
hyperlipidemia and atherosclerosis [16]. 5–Aminoimidazole–4–carboxamide–1–b–D–
ribofuranoside (AICAR) is one of the activators of AMPK
... Get more on HelpWriting.net ...

Lipid Medication Therapy: A Case Study
As important as medication therapy is, there seems to be gender disparities with the management of
lipid lowering medication therapy. Women are not being as aggressively treated as their male
counterparts, despite the higher baseline levels of LDL cholesterol. In Addition, women are not as
likely to continue the lipid lowering therapy in the long term due possibly to the side effects of
continued therapy. Providers need to increase their awareness of the cardiovascular risks of women,
including addressing the barriers of assessment, lipid screening, and targeted therapies, especially
for those most at risk. (Rodriguez, 2016)
One classification of medication used is the bile acid sequestrants. Bile Acid sequestrants, such as
Questran or Colestid, ... Show more content on Helpwriting.net ...
(2017, November 28). Retrieved April 5, 2018, from https://www.cdc.gov/heartdisease/facts.htm
Centers for Disease Control and Prevention. (2015, April 30). Retrieved April 5, 2018, from
https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_cholesterol.htm
Hinkle, Janice L., Kerry Cheever. Hinkle & Cheever: Brunner & Suddarth's Textbook of Medical–
Surgical Nursing, 13th Edition. CoursePoint, 11/2013. VitalBook file.
Ricci, Susan. Maternity and Pediatric Nursing, 2nd Edition. Wolters Kluwer Health, 11/2012.
VitalBook file.
Rodriguez, F., Olufade, T. O., Ramey, D. R., Friedman, H. S., Navaratnam, P., Heithoff, K., &
Foody, J. M. (2016). Gender Disparities in Lipid–Lowering Therapy in Cardiovascular Disease:
Insights from a Managed Care Population. Journal of Womens Health, 25(7), 697–706.
doi:10.1089/jwh.2015.5282
Soran, H., Dent, R., & Durrington, P. (2017). Evidence–based goals in LDL–C reduction. Clinical
Research in Cardiology, 106(4), 237–248. http://doi.org.starkstate.idm.oclc.org/10.1007/s00392–
016–1069–7
Versmissen, J., Vongpromek, R., Yahya, R., van der Net, J. B., van Vark‐van der Zee, L.,
Blommesteijn‐Touw, J., ... Sijbrands, E. J. G. (2016). Familial hypercholesterolemia: cholesterol
efflux and coronary disease. European Journal of Clinical Investigation, 46(7), 643–650.

Pros And Cons Of Nuclear Cloning
The quantity of organs available for transplantation is already far less than the authoritative
ordinance, and the ordinant dictation may grow substantially in the near future. For this reason, it is
timely to consider how organ function might be superseded in the future. In this communication, we
consider incipient technologies that might be habituated to supersede organ function, the obstacles
to applying incipient technologies and now those obstacles might be overcome in the developing of
incipient strategies for organ supersession. the obstacles of organ supersession might be addressed if
verious technologies could be pieced together in a way that exploits the advantages of each
technology. Thus, nuclear cloning (the transfer of a nuclei

Sepsis Case Studies
Sepsis is one of the leading causes of morbidity and mortality globally, the 10th leading cause of
death in the United States and the second leading cause of death in non–cardiac intensive care units
[1]. Each year between 400,000 and 500,000 cases of sepsis occur in the United States and the cost
of caring for a septic patient is high, resulting in a national economic burden of almost 17 billion
dollars per year [1–2]. Sepsis is a serious health concern and a better understanding of the causes
and potential interventions is necessary. Since 1987, gram–positive bacteria have been the major
causative agents of sepsis [1]. Staphylococcus aureus and Staphylococcus epidermidis are two of
these causative agents and together cause the majority of nosocomial sepsis infections in United
States hospitals [3]. Forty percent of the S. aureus strains, that cause an estimated 292,000
hospitalizations in the United States each year, are resistant to the first line option of antimicrobial
therapy, methicillin/nafcillin (β–lactamase resistant penicillins), making them extremely difficult to
treat [4]. ... Show more content on Helpwriting.net ...
The conversion of HMG–CoA to mevalonate by this enzyme is an early rate–limiting step in
isoprenoid biosynthesis [5]. There are two distinct classes of HMG–CoA reductase; class I enzyme
is present in mammals, plants, yeast, and most archaea, while the class II HMG–CoA reductase is
present in prokaryotes [6]. The class II enzyme has been shown to be present in bacterial pathogens,
including S. aureus and S. epidermidis and a functional mevalonate pathway has also been shown to
be essential for the viability of these gram–positive pathogens [7]. Additionally, purified class II
enzymes are four orders of magnitude less sensitive to competitive inhibition by statins than their
class I counterparts

Cardiovascular Disease, Atherosclerosis Essay
One source of great mortality and morbidity in Europe and North America is the cardiovascular
disease, Atherosclerosis. It is recognized as a chronic inflammatory disease of the intermediate and
large arteries characterized by the thickening of the arterial wall and is the primary cause of
coronary and cerebrovascular heart disease (Wilson, 2005). It accounts for 4.35 million deaths in
Europe and 35% death in the UK each year. Mortality rate are generally higher in men than pre–
menopausal woman. Past the menopause, a woman's risk is similar to a man's (George and
Johnston, 2010). Clinical trials have confirmed that lipid accumulation, endothelial dysfunction, cell
proliferation, inflammation matrix alteration and foam cell formation are ... Show more content on
Helpwriting.net ...
Macrophage which is now foam–like accumulates on the blood vessel to form visible fatty streak
which then undergoes apoptosis. The plaque continues to grow and hardens narrowing the arteries.
This ruptures and causes a blood clot which limits the flow of oxygen–rich blood to the body
causing a heart attack, stroke or even death. Factors that are known to predispose to atherosclerosis
are physical inactivity, diabetes mellitus, hyperlipidemia, cigarette smoking and hypertension which
increase the chances by two–fold by damaging the vascular endothelium. Experimental studies have
just shown that excess blood levels of iron can lead to atherosclerosis (Guyton and Hall, 2011).
2.0 Molecular and Cell–based therapies
Presently, the treatment strategies used are risk factor modification, conventional pharmacology and
surgical revascularization. These strategies have hitherto not been of enormous solution as the
disease progression still result in recurrent symptoms. This has now led to the exploitation of
advances in comprehending the vascular biology of atherogenesis to introduce novel cell and
molecular–based therapies. The application of immunomodulation, lipid–lowering agents like
statins, gene transfer, antisense technology and so on has resulted in new therapeutic strategies to
interrupt cell proliferation and disorder of the vessel wall. In this essay, immunomudulation and
lipid–lowering agent shall be discussed.
2.1 Immunomodulation

Medication Interview Research Paper
Medications Interview How much knowledge do we have about the medications that we are
prescribed from our physician? We don't always as patients get to much knowledge about the
medications from our doctor and we rarely ask the pharmacist about any concerns, and how many of
us really have taken the time to read the description of the medications that is stapled onto the
medication bag. I must confess I am not very good about that myself. This interview will be with
subject Jane Doe 67 years of age; Jane Doe has a history of acid reflux, low potassium, high blood
pressure, and high cholesterol. Ms. Jane Doe is very much aware of what each medication is used
for she was a Geriatric Nursing Assistant and Medicine Aide for a period of thirty–five years at a
nursing facility in Southern Maryland. She has been currently using these medications on a daily
basis, Protonix 40 mg (generic name pantoprazole sodium), Potassium CL 20 mg, and Atorvastatin
Calcium 10mg (generic name Lipitor). Hyzarr HTC. ... Show more content on Helpwriting.net ...
Protonix (pantoprazole) is used to treat such conditions where there is too much acid in the stomach.
It is also use to treat heartburn caused by gastroesophageal reflux disease (GERD), a condition
where the acid in the stomach comes back up into the esophagus. Side effects protonix may include
such symptoms of low magnesium such as fast or uneven heart rate; jerking muscle movements;
feeling jittery; diarrhea that is watery or bloody; muscle cramps, muscle weakness or limp feeling;
cough or choking feeling; or headache, trouble concentrating, memory problems, weakness, loss of
appetite. Before taking protonix (pantoprazole) inform the doctor of any allergies or any other drugs
similar to do it. This drug is to be swallowed it is a delayed–released tablet. Do not split, crush, or
chew it. You can take the tablet with or without

Statin Pills, Including Lipitor, Which Can Be Prescribed
Statin pills, including Lipitor, which can be prescribed to decrease cholesterol levels, paintings
partly through interfering with the activity of HMG–CoA reductase. If your cells take place to want
more LDL cholesterol below certain circumstances, but the statin drug is blockading this essential
enzyme, your cells won 't be able to make cholesterol whilst wished. And what's worse is that the
cholesterol synthesis pathway doesn't just make LDL cholesterol; branches of this same pathway are
liable for synthesizing a wide type of different important molecules along with nutrition A, nutrition
E, diet ok, and Coenzyme Q. So, you could want to suppose twice before you artificially intrude
with this pathway by taking a statin drug. ... Show more content on Helpwriting.net ...
It 's miles typically concept of as correct LDL cholesterol so better HDL levels are taken into
consideration an amazing signal. LDL debris carry greater cholesterol made within the liver out to
the relaxation of the cells within the frame. We used to think of LDL as awful LDL cholesterol so
lower levels of LDL have been considered an excellent signal.
The LDL cholesterol inside of HDL and LDL particles is precisely the identical, it's just that, for the
maximum part, HDL is wearing it in one path and LDL is sporting it in the opposite route. The
reason why LDL were dubbed horrific and HDL has been dubbed excellent is that numerous
epidemiological studies most famously, the Framingham heart study told us that excessive LDL
levels had been related to a better chance of heart assault, and that high HDL levels have been
related to a lower risk of heart assault.
We used to suppose that HDL changed into desirable as it acted like a rubbish truck, clearing evil
cholesterol out of our bodies, and we used to assume that LDL was awful because it burrowed its
manner into our coronary arteries, depositing evil cholesterol there forming plaques and causing
coronary heart attacks.
Cholesterol, Carbohydrates and Heart Disorder
However, this simplistic way of thinking about cholesterol and heart disease is changing before our
very eyes. It turns out that it 's miles more complex than

Cholestrol-lowering Drugs Essay
Cholestrol–lowering Drugs
Thirteen years ago, cholesterol–lowering drugs called statins were introduced as a treatment for
people with heart disease. In the relatively short amount of time the drug has been available, it has
been prescribed to nearly five million people. Originally, statins were introduced to prevent heart
attacks and prolong the lives of people with existing heart disease or with a history of heart disease.
Recently, however, studies have shown that statins are not only useful for the treatment of heart
disease, but are also useful in the lowering of cholesterol levels.
Although statins have few known side effects, many doctors believe that the drugs are too new to
rule out the possibility of more. The known side ... Show more content on Helpwriting.net ...
floating in the bloodstream, leaving less of the dangerous form of cholesterol to accumulate in blood
vessels. This lowering of the amount of L.D.L. in the blood stream benefits the heart by stopping
plaque from building up and possibly rupturing, forming a clot that can impede blood flow and in
turn kill oxygen starved tissue.
The information in the article about the reduction of cholesterol levels by stations helped me to
better understand the practical uses for the inhibition of enzymes and also learn more about the role
cholesterol plays in the body and in cellular functions. In lecture, I learned about both cholesterol
and enzymes, but before reading the article, I did not fully understand the connection between the
two. By reading the article, I learned many things about cholesterol that I did not previously know. I
learned how cholesterol can have both positive and negative effects on the body. I learned that
although cholesterol is needed for all cellular functions, it can also negatively effect the body by
forming plaque which could possibly break apart forming clots which stop blood flow to important
tissues. Finally, I learned that L.D.L. or low––density lipoprotein is the "bad" form of cholesterol
that floats around in the bloodstream and that it is the type of cholesterol which is responsible for
causing the clots which have the possibility of harming important organs such as the heart.
Another important thing I learned from the article on statins

Calcium Hardness And Shell Thickness
On the other hand, addition of probiotic had no significant effect (P>0.05) on shell hardness and
shell thickness and these were expected which have already been reported (Haddadin et al., 1996;
Chen and Chen 2003). Although, the increase of albumen quality wasn't significant (P > 0.05), no
reasonable explanation can be offered for the improvement in albumen quality in the microbial
additive groups. Jensen et al. (1978) found significant improvements in interior egg quality which
measured by Hough Units in hens fed distillers feeds and corn fermentation soluble. Subsequent
studies indicated that trace elements was been involved (Jensen and Maurice, 1978). But Tortuero
and Fernandez (1995) described that the difference in plasma mineral concentration were not
sufficient to implicate supporting the hypothesis that trace elements were improved albumen quality
with microbial supplementation. Addition of probiotic had significant effect on egg yolk cholesterol
(mg /g of yolk). Haddadin et al. (1996) observed similar results. They reported that inclusion of
probiotic lactobacillus acidophilus in different ages (40, 44 and 48 week) affects egg cholesterol in
40 week of production not 44 and 48. These results have already been confirmed by Marks and
Washburn (1991) reports.
Blood parameters The effects of dietary AA and LAB supplementation on serum parameters are
summarized in Table 3. Serum glucose, ALT and triglyceride were decreased by feeding AA or LAB
but not

Pitavastatin Research Paper
LIVALO (pitavastatin) is an inhibitor of HMG–CoA reductase. It is a manufactured lipid–bringing
down specialist for oral administration. The compound name for pitavastatin is (+) monocalcium bis
{(3R, 5S, 6E) – 7–[2–cyclopropyl–4–(4–fluorophenyl)– 3–quinolyl]–3,5dihydroxy–6–heptenoate}.
The basic recipe is: The experimental equation for pitavastatin is C50H46CaF2N2O8 and the atomic
weight is 880.98. Pitavastatin is unscented and happens as white to light yellow powder. It is
uninhibitedly solvent in pyridine, chloroform, weaken hydrochloric corrosive, and tetrahydrofuran,
dissolvable in ethylene glycol, sparingly solvent in octanol, marginally solvent in methanol,
somewhat solvent in water or ethanol, and for all intents and purposes insoluble ... Show more
content on Helpwriting.net ...
Thus, the declaration of LDL–receptors took after by the take–up of LDL from blood to liver is
quickened and afterward, the plasma TC diminishes. Further, the supported hindrance of cholesterol
amalgamation in the liver declines levels of low–thickness lipoproteins. Identify the drug as either a
competitive or allosteric inhibitor. How it works? 1. Pitavastatin is a powerful aggressive inhibitor
of HMG–CoA reductase little used in hepatic microsomes. Pitavastatin lactone, which can be
changed over back to the unaltered shape, is the real metabolite of pitavastatin in people. To
elucidate the instrument of the lactonization of pitavastatin and the metabolic properties of the
lactone, we performed explores in vitro. 2. On expansion of UDP–glucuronic corrosive, human
hepatic microsomes created pitavastatin lactone and an obscure metabolite (UM–2). UM–2 was
changed over to its unaltered shape by enzymatic hydrolysis and to a lactone frame non–
enzymatically. Utilizing a few human UGT–communicating microsomes, UGT1A3 and UGT2B7
were mainly in charge of glucuronidation of pitavastatin prompting

Carmonic-Tonic Seizure: A Case Study
The first line therapy for treatment of clonic–tonic seizure are carbamazepine, phenytoin, valproic,
and fosphenytoin. Phenytoin (Dilantin) is a first line, single therapy to treat both partial and
generalized tonic–clinic seizures. The medication is also used to prevent seizures after brain surgery.
Phenytoin works by suppressing of the sodium action potential and filtering out of sustained high–
frequency neuronal discharges and synaptic activity. Through this action, phenytoin obstructs the
positive feedback that underlies the development of maximal seizure activity, while normal brain
activity. The loading dose of dilantin initially start at 15 to 20 mg/kg/day, then increase weekly if
needed. Maximum (maintenance) dose is 300 mg 3 times ... Show more content on Helpwriting.net
...
The examples of drugs in this class are atorvastatin (Lipitor), rosuvastatin (Crestor), and simvastatin
(Zocor). Statins is the first line to use for lowing blood cholesterol levels. Statins works by blocking
the enzyme called HMG–CoA reductase in the liver which is necessary for making cholesterol. The
statins blocks the active site of the HMG–CoA reductase enzyme so that it cannot converse to
mevalonate. Therefore, there is more LDL receptor available in the liver. These receptors bind to
passing LDL and VLDL (very low–density lipoprotein). The LDL and VLDL then enter the liver
and are digested. So that there is less LDL level in blood stream. Even though, many drugs are in
the same class, but the effectiveness of each drug is different. For example, 5–40 mg of Crestor
seems to work best by lowering LDL by 47–65%; whereas 10–40 mg of pravachol can lower LDL
by 22–34%. Most people who take statins do not experience serious side effects. The most common
minor side effects include headache, pins and needle sensations, abdominal pain, bloating, diarrhea,
feeling sick, and a rash. The provider normally starts statins in a low. The dosage may be increased
if this target is not reached. Statins are contradicated in patient with active liver disease and
consume a large amount of alcohol. The common side effects are GI upset and

Agiotensin Beta Blocker
According to National Clearinghouse Guidelines, several classes of drugs should be considered in
the treatment of systolic heart failure. Angiotensin–converting Enzyme (ACE) inhibitors and Beta
Blockers are the treatment of choice for systolic heart failure. Some beta–blockers have
demonstrated the benefit of improving clinical symptoms, increasing ventricular function, and
decreasing hospitalizations and mortality in systolic heart failure patients. If Ms. Boehmer has
intolerance to ACE inhibitors, she may benefit from the combination of Hydralazine and Isosorbide
dinitrate (especially beneficial for African Americans with heart failure) or Angiotensin II receptor
blockers (ARB). Digoxin can improve Ms. Boehmer's symptoms. Digoxin is beneficial ... Show
more content on Helpwriting.net ...
It blocks the angiotensin converting enzyme and inhibit the conversion of angiotensin I to
angiotensin II leading to decreased vasoconstriction, and result in reduced blood pressure.
Aldosterone secretions is also blocked, therefore decrease sodium and water reabsorption. Beta–
blockers prevents the stimulation of the beta adrenergic receptors at the nerve endings of the SNS,
therefore decrease the activity of the heart. It reduces the oxygen demand by reducing the systolic
pressure, heart rate, contractility and output. Hydralazine and Isosorbide dinitrate decrease the
afterload. Hydralazine and isosorbide are vasodilators, which decrease the resistance of the blood
vessels. The combination decreases the workload of the heart. ARBs is to bind with angiotensin II
receptors and decrease the effect of angiotensin II. It decreases the preload and afterload. It blocks
the vasoconstriction effect, increases heart rate and contractility of the heart. It also blocks the
stimulation of aldosterone secretions, which further prevents sodium and water retention. Digoxin
increases the force contraction of the heart, therefore increase contractility and cardiac output to
improve the symptoms of heart failure. Diuretics is used to reduce preload, to prevent water and
sodium reabsorption to maintain appropriate fluid balance. Aldosterone antagonist blocks the body's
response to the hormone aldosterone. It prevents sodium and water retention

Advantages And Characteristics Of Medicinal And Aromatic...
1.2.1 Medicinal and Aromatic plants. World Health Organization (WHO) reported that nearly 80%
of the planet's population, exclusively in developing countries, still depends on plants for their
healthcare (Gurib–Fakim, 2006). Plants, predominantly applied for their medicinal or aromatic
properties in pharmacy and perfumery are categorized as medicinal and aromatic plants,
respectively (Lubbe and Verpoorte, 2011). Aromatic plants have a unique aroma and flavour due to
some types of compounds, known as phytochemicals or secondary metabolites (Fisher, 1992). Most
of the secondary metabolites have antimicrobial activity through substances present in aromatic
plants. Several classes of phytochemicals, including anthocyanins, isoflavones, flavonoids ... Show
Heteromeric GPPSs are formed by the combination of two sub–units, the small subunit (GPPS.SSU)
which is catalytically inactive while another is large subunit (GPPS.LSU). The catalytic activity of
GPPS.LSU varies within plant species. The small subunit (GPPS.SSU) interacts with GPPS.LSU to
form the heteromeric enzyme, which catalyzes the synthesis of GPP (Tholl et al., 2004; Wang and
Dixon, 2009). Moreover, GPPS.SSU also interacts with GGPPSs from distant plant species (Wang
and Dixon, 2009). The physical interaction between two subunits is critical for the formation of
GPP, which was investigated in peppermint GPPS as heterotetrameric structure (Chang et al., 2010).
Moreover, A. thaliana and many other seed plants were having domains closely related to the SSU
of the heteromeric GPPS and it got annotated as SSUII (Wang and Dixon, 2009). The GPPS.SSU
performs a key role in formation of GPP for monoterpenes by modifying the product specificity of
LSU/GGPPS. The characterized GPPS–LSUs and homomeric GGPPSs from different plants
showed highly similarity among each other (>65%) and produced various products as far as the
enzymatic activity is concerned. For instance, LSU from M. piperita was the only member reported
to be catalytically inactive, while all other LSU reported from different plants were catalytically
active, like LSU from A. majus was active as GGPPS and LSU from H. lupulus required GGPP in
addition to GPP and FPP (Burke et al., 1999; Tholl et al., 2004; Wang and Dixon, 2009). In
comparison to LSUs, SSUs were catalytically inactive and showed much lower sequence identity
(20–30%) with plant GGPPSs and homomeric GPPSs (Burke et al., 1999;

Simovastatin Essay
Statins are recommended as a first–line therapy for the management of lipid disorders, particularly
elevations in low–density lipoprotein cholesterol. In the 1950s and 1960s, it became obvious that
elevated concentrations of plasma cholesterol represent a major risk factor for the development of
heart disease, which led to the quest for drugs that could reduce it.
Since lovastatin had been commercialized, six statins – including two semi–synthetic statins (known
as simvastatin and pravastatin) and four synthetic statins (fluvastatin, rosuvastatin and pitavastatin
and atorvastatin) – have been introduced to the market. The most popular statin today is atorvastatin.
The discovery of statins
While working at the Sankyo Company in 1976, the Japanese biochemist Akira Endo isolated a
factor from the fungus Penicillium citrinum which he identified as a competitive inhibitor of 3–
hydroxy–3–methyl–glutaryl–coenzyme A ... Show more content on Helpwriting.net ...
Nevertheless, some researchers stayed skeptical as compactin did not lower plasma cholesterol in
the rat, which was subsequently demonstrated to result from massive induction of HMG–CoA
reductase in rat liver by inhibitors of the enzyme.
Clinical studies of compactin in Japan ensued soon after that, as well as experimental studies around
the world. In 1978, Alfred Alberts with his colleagues at Merck Research Laboratories discovered a
potent inhibitor of HMG–CoA reductase in a fermentation broth of Aspergillus terreus, which was
named lovastatin, mevinolin or monacolin K. Conicidentally, Akira Endo independently identified a
same compound within a year of Alberts' discovery.
After animal safety studies have shown no adverse effects, Merck began clinical trials of lovastatin
in April 1980. Still, promising start was interrupted because the trials with structurally similar
compactin were stopped by Sankyo Company in September 1980, supposedly due to serious animal

Baycol Research Paper
Description
Baycol is a drug containing 0.2, 0.3, 0.4 or 0.8 mg of the active ingredient cerivastatin sodium and
inactive ingredients: mannitol, magnesium stearate, sodium hydroxide, crospovidone, povidone,
iron oxide yellow, methylhydroxypropylcellulose, polyethylene glycol, and titanium dioxide.
Cerivastatin sodium is sodium (C26H33FNO5Na) with molecular weight of 481.5 and the following
chemical structure:
Clinical Pharmacology
Baycol is a drug that was used to reduce cardiovascular diseases created by the pharmaceutical
company Bayer. This drug is part of the class of statins. This class of drugs reduces the cholesterol
level in the blood decreased cholesterol production by liver shutting down the enzyme responsible
for its production. The enzyme is called hydroxy–methylglutaryl–coenzyme A reductase ... Show
The studies have incorporated more than 5,000 patients with Type IIa and IIb hypercholesterolemia
treated in trials periods of 4 to 104 weeks.
Patents and Trademarks
FDA approved the application of Baycol in June 26, 1997, after a period of 2,262 days for
applicable regulatory review. The testing phase occurred during 1,896 days, while the approval
phase occurred in 366 days.
Baycol was marketed by Bayer A.G. until 2001, competing with Pfizer's highly successful
atorvastatin (Lipitor). Voluntarily in 2001 Cerivastatin was withdrawn from the market due to
reports of fatal rhabdomyolysis.
Post– market
During the practice of monitoring the safety of Baycol (postmarketing surveillance), 52 deaths and
385 nonfatal cases were reported in patients using cerivastatin due rhabdomyolysis. The cerivastatin
caused 16 to 80 times more deaths than other statins. In 2002, over 100 deaths were reported due

Fluvastatin Lab Report
Hypothesis
If the drug Fluvastatin lowers LDL cholesterol, then the people with high LDL cholesterol who take
fluvastatin will have low LDL cholesterol levels. Introduction
Fluvastatin is a highly regarded drug that is involved with treating hypercholesterolemia and
preventing cardiovascular disease. The drug is used to lower both high cholesterol and triglycerides
levels. The drug is able to perform this task by increasing good cholesterol levels (HDL) while, at
the same time, reducing bad cholesterol levels (LDL). Fluvastatin decreases the production of bad
cholesterol by blocking the action of the enzyme HMG– CoA reductase in the liver. This results in a
decrease in the amount of cholesterol in liver cells and subsequently leads it

Cataractogenesis
Cataractogenesis, or opacification of the ocular lens of the eyes (cataracts), is a multifactorial
process that may be initiated by oxidative damage from oxygen radicals [1]. Cataracts are the
world's leading cause of blindness, accounting for approximately 42% of all cases of blindness in all
nations [1,2]. In most cases, cataracts are age–related [3,4]; in other cases, it may be related to eye
trauma, long–term diabetes, corticosteroid medications or radiation treatments [5]. Although surgery
is often effective in restoring vision [6], this intervention still remains a major healthcare cost in
Europe and other Western countries [7]. The concern about statin cataractogenicity arose in the
1980s, when the Food and Drug Administration approved lovastatin with the precaution that patients
should be examined with a slit–lamp before and during ... Show more content on Helpwriting.net ...
In a meta–analysis on both randomized control trials (RCTs) and observational studies performed by
Kostis and Dobrzynski, statin use was associated with a 19% decrease in the risk of cataract [11].
After publication of this meta–analysis, Leuschen et al. published a propensity score–matched
analysis that indicated an increased risk of cataract among statin users as compared to non–users
[12]. Furthermore, Lai et al. conducted a retrospective cohort study using the Longitudinal Health
Insurance Database of Taiwan, showing that statin therapy was associated with a modestly increased
risk of cataract surgery [13], and Wise et al. showed that statin use is significantly associated with
cataract requiring surgical intervention in two large North American cohorts [14]. So far studies that
explored the association between statin use and the incidence of cataract have been inconsistent and
controversial; the objective of the current study was to further explore the influence of statin therapy
on the development of cataracts in the general population of Northern

The Effects Of Statins On The Treatment Of Many Diseases
Statins are drugs used in the treatment of many diseases including hypercholesterolemia, ischemic
heart disease (angina, chronic heart disease and myocardial infarction), cerebrovascular accidents
and peripheral arterial disease. Adults with a history of cardiovascular disease (CVD) or those with
a 10–year risk of developing CVD should start statin therapy as a prophylactic measure. As a result
of all these indications, statins are one of the world's most prescribed drugs (1).
Many forms of statins are present in the markets including atorvastatin (Lipitor), lovastatin
(Mevacor, Altocor) and simvastatin (Zocor). Inhibition of 3–hydroxy–3–methyl glutaryl coenzyme
A reductase (HMG–CoA reductase), a key enzyme in the cholesterol biosynthetic pathway is the
mode of action of most of the statins (2).
Many side–effects must be understood and prevented throughout the use of statins. The most severe
side–effect is rhabdomyolysis, which is characterized by damaging of the skeletal muscle which
leads to the release of muscle proteins into the blood (3). Statin induces rhabdomyolysis that can be
acute, subacute, or chronic, and may be permanent despite dose reduction or substitutions (4).
Myoglobin release from the damaged muscle can lead to acute renal failure. All statins have been
associated with adverse muscle events (5).
Statins lower the concentration of low–density lipoprotein cholesterol and very–low–density
lipoprotein cholesterol in people with elevated triglycerides. Many

Alzheimer 's Disease : Causes Progressive Physical And...
Alzheimer's disease (AD) can be described as a neurodegenerative disease that causes progressive
physical and cognitive decline.1 AD which is mostly seen in the elderly, is the most common form
of dementia. Dementia can be described as the loss of the brain's ability to function in multiple ways
in a person who is awake or alert. Dementia includes memory loss and also affects a person's ability
to speak, read, write, listen, and complete certain tasks.1 Dementia can have a tremendous impact
on one's behavior and emotions and can range from being a mild case to being totally disabling.
There are several types of dementia with AD being the most common, which primarily affects the
elderly and is usually irreversible and non–curable. Although not all dementia is AD, it does
however account for up to fifty to seventy–five percent of dementia cases.2 Over 5 million
Americans have AD, and it is estimated that by the year 2050 this number will have increased up to
14 million.2 One out of every ten people, ages sixty–five years and older develops AD and some
may even develop the disease in their forty's and fifty's.2 Dr. Alois Alzheimer, who was a
neuropathologist as well as a psychiatrist, discovered what is known today as AD.3 One of Dr.
Alzhiemer's patients was a fifty–one year old woman with severe dementia. He studied this patient
until she died, which then gave him the opportunity to study her brain.3 By examining this patient's
brain he noticed how the cerebral cortex (the

The Consequences Of Animal Production
From both an environmental, as well as economic standpoint, it is in the best interest of cattle
producers to decrease methane emissions, limit their contribution to climate change, and improve
overall animal feed efficiency (Beauchemin et al., 2008). There are several options for reducing
methane emissions, which can be collectively grouped into three broad categories. These categories
include increasing animal production via genetics and management, modifications to feeds, feeding
management, and nutrition (including intake, roughage type/ quality, forage to concentrate ratio,
feed processing, total mixed rations/ feeding frequency, and precision feeding/ feed analysis), and
supplementation with rumen modifiers (including plant ... Show more content on Helpwriting.net ...
In regards to fatty acid profile of the diet, the inclusion of mono– and polyunsaturated fat have a
profound effect on methane production, with little to no effect with differences in total concentration
of saturated fat (Beauchemin et al., 2008; Grainger and Beauchemin, 2011; Patra, 2013). Among the
various types of fat used in research to potentially reduce methane emissions, the use of
polyunsaturated fat (oil) has been demonstrated to have the most extensive methane reduction
properties (Patra, 2013). Among these fats, the most common are soybean oil, linseed oil, and
sunflower oil; however, canola oil has recently increased in popularity due to its economic
importance and availability, specifically in western Canada, where over 18 MMT of canola are
produced annually (Patra, 2013; Statistics Canada, 2016). Although there are few studies using
canola oil as a methane inhibitor (Beauchemin and McGinn, 2006a,b; Brask et al., 2013; Pinares–
Patiño et al., 2016), when supplemented at around 3–5% of DM in vivo in dairy and beef cattle,
canola oil reduced methane emissions (g/d and g/kg of DMI) and had no effect on total VFA
concentration, no effect or decrease in acetate, no effect or increase in propionate, and no effect or
decrease in acetate:propionate ratio. Canola oil also demonstrated variable results regarding effect
on DMI and diet digestiblities. Again, the effect of fat on methane emissions and other parameters
tends to be variable when

Cholesterol Essay
Cholesterol is an essential molecule for animal life. It is an integral component of the plasma
membrane of animal cells, it is a precursor of steroid hormones and bile acids, and it plays a crucial
role in the formation of the myelin sheath that surrounds axons. Cholesterol and other insoluble
lipids are transported through the bloodstream in lipoprotein particles. Lipoproteins are a family of
globular particles comprised of a core of neutral lipids surrounded by cholesterol, phospholipids,
and apoproteins. Low density lipoprotein (LDL) and high density lipoprotein (HDL) are the two
primary carriers of cholesterol in the blood. The primary function of LDL is to deliver cholesterol to
cells throughout the body, where it is removed from ... Show more content on Helpwriting.net ...
From an early age, these individuals are at high risk for atherosclerosis and heart disease.
Heterozygous FH individuals are also at risk for these diseases, albeit to a much lesser degree.
Because the FH mutation also caused the disease in heterozygous individuals, Goldstein and Brown
began with the assumption that FH was the result of a defect in regulation of cholesterol synthesis.
Discovery of the LDL Receptor
Goldstein and Brown began their work by measuring the activity of 3–hydroxy–3–methylglutaryl
coenzyme A reductase (HMG CoA reductase), which catalyzes the rate–limiting step in cholesterol
production. Goldstein and Brown found that when normal fibroblasts were grown in serum, HMG
CoA reductase activity was low. Additionally, they found that when cholesterol–carrying
lipoproteins was removed from the culture medium, HMG CoA reductase activity increased by a
large margin. Furthermore, they observed that HMG CoA reductase activity was suppressed when
LDL was reintroduced to the medium. This inhibition of HMG CoA reductase by LDL, and the fact
that low concentrations of LDL suppressed HMG CoA reductase activity, led Goldstein and Brown
to believe that a receptor with high affinity for LDL was involved in the inhibition of cholesterol
synthesis.
When Goldstein and Brown measured HMG CoA reductase activity in FH homozygous fibroblasts
grown in normal serum, they came to the conclusion that HMG CoA reductase activity was not
affected by the presence of LDL in

Sepsis Case Studies
Thirty to 50 percent of the 400,000 to 500,000 cases of sepsis in the United States each year are
fatal, emphasizing the seriousness of this public health concern [2]. Recent research into possible
alternative treatment options indicates that patients being treated with statin therapy are less likely to
develop sepsis from a serious infection, die from sepsis or develop serious complications due to
sepsis; however, the mechanism of action is unknown and therefore is the focus of this study [2, 6,
10–12]. Possible mechanisms of action include a direct interaction of the statin with the sepsis–
causing organism, an interaction between the statin and the host immune system or a combination of
the two [9, 14, 16–17]. Additionally, recent studies indicate that statins may have a direct
antimicrobial effect and has suggested that statins may diminish the replication and infectivity of
some pathogens responsible for sepsis [11, 14, 16–17]. Thus, we hypothesized that statins could
benefit septic patients by ... Show more content on Helpwriting.net ...
epidermidis (Fig. 3). This effect began at hour 4 of unrestricted growth and continued up to 24 hours
(Fig. 3). Furthermore, atorvastatin treatment caused a significant increase in the generation time of
S. epidermidis over 18 hours. These repeatable effects appear to be species specific, as they did not
occur with any of the S. aureus strains tested. To further test the species specific hypothesis, we
generated 24 hour unrestricted growth curves with S. haemolyticus and E. faecalis, which have been
shown to have the same genes required for the isoprenoid biosynthesis pathway as S. epidermidis
and S. aureus [7]. S. haemolyticus and E. faecalis were unaffected by atorvastatin (60µM), leading
us to conclude that not only is this effect species specific to S. epidermidis, but also not all sepsis
pathogens respond to statin treatment in the same way, nor do they respond to all types of

Reaction Paper On Cholesterol
Essay 18: Cholesterol Explained
At this point in time, the word 'cholesterol' has a decidedly negative connotation, conjuring up
images of gallstones, heart attacks, and strokes. Although excess cholesterol often plays a role in
these disease states, that is only part of the story. This article will focus on what cholesterol is and
why the human body needs a certain amount of it to function properly. Cholesterol is a small,
hydrophobic molecule composed almost entirely of carbon and hydrogen atoms. The 27 carbon
atoms in cholesterol are all derived from the molecule acetyl CoA (coenzyme A), synthesized from
the breakdown of amino acids, sugars, and fats. Acetyl CoA is often channeled into the Krebs cycle
in order to harvest its chemical energy; however, it is also used as the initial compound in many
biosynthetic pathways. ... Show more content on Helpwriting.net ...
At this point, an enzyme called HMG CoA reductase catalyzes the committed step in the pathway,
turning HMG CoA into mevalonic acid. From there, a series of enzymes converts mevalonic acid
into squalene, a linear intermediate which folds to yield the four ringed structure of cholesterol.
Almost all cholesterol synthesis occurs in the liver, mainly because the liver is also the site of bile
acid production. In adults, the liver produces enough cholesterol to meet the body's needs. Dietary
cholesterol comes in the form of dairy products, eggs, red meat, and

Dunnets Test Using Graphpad
Statistical Analysis: All the results were expressed as mean±SEM and subjected to One–way
analysis of variance followed by dunnets test using GraphPad prism 5.0 Results : Effect on TC TC
levels were significantly elevated in positive control when compared with normal control. When
compare with normal control, standard group and ethanolic extract groups are significantly different
(F = 25.20, p<0.01). Standard group, ethanolic extract, and aqueous extracts groups are not
significant When compared with positive control. (Figure–1) Effect on TG TG levels were
significantly elevated in positive control when compared with normal control. When compare with
normal control, standard group, ethanolic extract, and aqueous extracts groups are not statistically
significant. Normal controls, standard group, ethanolic ... Show more content on Helpwriting.net ...
Normal controls, standard groups are statistically significant when compared with positive control
(F = 12.86, p<0.001). Ethanolic and aqueous extracts raised the HDL levels but the raise is not
statistically significant. (Figure–3) Effect on LDL LDL levels were significantly elevated in positive
control when compared with normal control (F = 15.94, p<0.001). Standard group and aqueous
extracts group has decreased the LDL levels but the decrease is not statistically significant. (Figure–
4) Effect on VLDL VLDL levels were significantly elevated in positive control when compared with
normal control. When compare with normal control, standard group, ethanolic extract, and aqueous
extracts groups are not statistically significant. Normal controls, standard group, ethanolic extract
and aqueous extracts groups are statistically significant when compared with positive control (F =
15.32, p<0.001). This indicates that both aqueous and ethanolic extract treatment has reduced the
VLDL levels in the rats. (Figure–5) Effect on AI and

Mevalonate Lab Report
The first reaction in the mevalonate pathway begins with the cytosolic enzyme acetoacetyl–CoA
thiolase, which condenses two acetyl–CoA molecules to produce acetoacetyl–CoA. In the next step,
which is catalyzed by HMG–CoA synthase, acetoacetyl–CoA is condensed with acetyl–CoA to
produce HMG–CoA. HMG–CoA reductase, the rate–limiting enzyme of the mevalonate pathway,
converts HMG–CoA to mevalonate in a two–step reaction, using two molecules of NADPH
(Grunler et al., 1994; Kuzuyama, 2002). Mevalonic acid (mevalonate) is gradually converted into
the 5–carbon molecule isopentenyl–pyrophosphate (IPP) via a multi–step phosphorylation and
decarboxylation reactions then on to the 15–carbon molecule farnesyl–pyrophosphate (FPP) that is
the substrate for ... Show more content on Helpwriting.net ...
Cholesterol is incorporated by lipoproteins in the cell membrane and regulates membrane fluidity.
Cholesterol is also important for the production of steroid hormones in mammals and cell signaling
(Devarenne et al., 2002). Although, insects and vertebrates have cholesterol as the main source of
body sterol, they lack the enzymes required for de novo sterol biosynthesis; they must obtain sterols
from their diet (Clark and Block, 1959; Jing et al., 2013). Nematodes are also cholesterol
auxotrophs. In nature, the main sources of sterols for C. elegans are animal feces or yeast/plant
debris whereas in laboratory condition C. elegans is maintained on agar plates containing
cholesterol (Matyash et al., 2001). Cholesterol is an essential nutrient supplement affecting several
development processes in C. elegans including molting, reproduction, dauer formation and
metabolism (Shim et al., 2002).Feeding worms with dehydroergosterol (DHE), a fluorescent analog
of cholesterol which mimics its property, revealed that DHE accumulates mainly in the pharynx,
nerve ring, excretory gland cell, as well as gut during the L1–L3 stages. During adulthood, DHE
molecules accumulate in oocytes and sperms, which is not surprising because these cells need high
levels of membrane components for the development and growth of embryos (Matyash et al., 2001).
Little is known about the molecular mechanism of cholesterol transport and its

Medicine : Patient Information Management
John Doolittle once said, "Developments in medical technology have long been confined to
procedural or pharmaceutical advances, while neglecting a most basic and essential component of
medicine: patient information management". Millions of Americans and citizens around the world
today are prescribed pharmaceutical drugs every year. Some are for simple things, such as allergies,
and others are for life threatening conditions if not treated properly, such as diabetes, heart disease,
and high cholesterol. Many people diagnosed with these drugs do not even really know what the
drugs in question do. In this paper, we will be discussing a few of many drugs that people are
prescribed to help them live their daily lives.
Before we can properly talk about pharmaceutical drugs, there are a few terms that we need to
define. The Merriam Webster dictionary defines the word pharmaceutical as," of or relating to the
production and sale of drugs and medicine". This means that a pharmaceutical drug is produced and
sold as a form of medicine. There is also a beta–blocker, which van be defined as, "medications that
reduce the blood pressure". These medications will slow down the heartbeat. There is also the term
low–density lipoprotein. Low–density lipoprotein is "bad cholesterol", or the cholesterol that will
block the arteries in the heart, causing blockage, and maybe heart attacks. The exact opposite to this
type of cholesterol is high–density lipoprotein; the kind that the body needs to

Ergotamine Research Paper
Antibiotics aren't the only use of fungus in medication, Ergot alkaloids are derived from the
common fungus Claviceps purpurea and have a number of medicinal uses; Ergotamine is prescribed
to relieve migraine headaches, it can also reduce blood pressure.
Ergonovine is used for preventing and treating bleeding after delivery of a baby or an abortion, it is
a uterine stimulant so works by increasing uterine contractions, which helps reduce the blood loss
after the baby is delivered.
Ergotamine and dihydroergotamine are less effective oxytocics than ergonovine, they can be given
orally or intravenously , it is currently used in obstetrics to treat or prevent post partum uterine atony
and to complete an incomplete or missed abortion.
Statins : ... Show more content on Helpwriting.net ...
Statins can reduce or remove low density lipoproteins from blood vessels in the human body, the
compounds act through an enzyme in the liver which produces cholesterol, lovastatin inhibits HMG
CoA reductase and squalestatin inhibits squalene synthase, it works by blocking the enzyme so the
body removes cholesterol complexes from the inside of blood vessels, thereby reducing or removing
blockages in the arteries, which in turn reduces the chance of a heart attack, strokes and diabetes.
Statins can also attract stem cells towards damaged tissues, so the stem cells then appear to
regenerate the tissue.
Griseofulvin is used in both animals and humans to treat fungal infections of the skin, hair and nails
(dermatophytes) ; such as Ringworm and nail fungus; it was discovered in 1939 from the mold
Penicillium patulum, Griseofulvin is listed on the World Health Organisation's List of Essential
Medicines. Administered

Mild Stress Theory
Unpredictable chronic mild stress induces anxiety and depression–likebehaviors and inactivates
AMP–activated protein kinase in mice.
Abstract
The unpredictable chronic mild stress (UCMS) model was developed based upon the stress–
diathesis hypothesis of depression. Most effects of UCMS can be reversed by antidepressants,
demonstrating a strong predictive validity of this model for depression. However, the mechanisms
underlying the effects induced by UCMS remain incompletely understood. Increasing evidence has
shown that AMP–activated protein kinase (AMPK) regulates intracellular energy metabolism and is
especially important for neurons because neurons are known to have small energy reserves.
Abnormalities in the AMPK pathway disturb normal ... Show more content on Helpwriting.net ...
Given that socio–environmental chronic stressors influence the development of depression, stress–
based animal models have been used to explore biological mechanisms of this disorder.
Unpredictable stressors have a greater negative impact than predictable stressors due to their
uncertainty (Bondi et al., 2008). Therefore, unpredictable chronic mild stress (UCMS) has been
developed as an experimental model of depression. Converging evidence has shown that UCMS
induces anhedonic–like behavior in mice (Mineur et al., 2006), but little is known about the
neurobiological mechanism of the abnormal behaviors caused by UCMS.
Several limbic brain regions, including prefrontal cortex, hippocampus, amygdala, and nucleus
accumbens (NAc), have been implicated in mediating key symptoms of depression and anxiety
(Keedwell et al., 2005; Krishnan and Nestler, 2008; Mayberg et al., 2005). Chronic exposure to
physical or psychological stress impairs the structure and function of neurons in prefrontal cortex
(Radley et al., 2006), hippocampus (Surget et al., 2011) and amygdala (Mozhui et al., 2010). These
changes depend on de novo synthesis of proteins involved in neural and synaptic plasticity. Synaptic
proteins such as synaptophysin (SYP) and drebrin play a critical role in synaptic plasticity (Aoki et
al., 2009; Janz et al., 1999). SYP is a major integral protein of the synaptic vesicle membrane and is
required for vesicle

Cla Research Paper
Mechanism of the Health–promoting Effects of the Food Ingredient
Evidence suggests that the biological effectiveness of CLA are due to the separate actions of cis– 9,
trans 11 and trans– 10, cis 12 isomers.It is likely that numerous health effects are enhanced by
synergistic actions of these isomers. Findings such as, inhibition of chemically induced
carcinogenesis, enhanced immune system, reduction of atherosclerosis, enhanced growth, fat
reduction are attributed to a mixture of these CLA isomers (Pariza, Park, & Cook, 2001).
Weight reduction
Researchers have theorized about the many mechanisms CLA have an effect on. Some proposed
mechanisms such as reduction of proliferation and differentiation of preadipocytes, decreased
esterification ... Show more content on Helpwriting.net ...
Insulin resistance can also be caused by increased triglycerides and free fatty acids intake. This is
due to the effect Triglycerides and free fatty acids have on insulin stimulated signal pathways,
translocation protein–4 and glucose uptake (Choi, Jung, Park, & Song, 2004). It is found that CLA
has a regulatory effect on glucose and lipid metabolism regulators. CLA affects the PPAR–y ligand,
a major receptor that influences the expression and transcription of genes that are related to the
metabolic effects of glucose and lipids. Such protein regulators as aP2, insulin–dependent glucose
transporter 4, FATp, ACS and adiponectin are all influenced by increased CLA. (Xiao–Rong Zhoua,
Chang–Hao Suna, Jia–Ren Liua, b, Dan Zhaoa, 2008). It was also theorized that CLA may act on
other glucose regulators such as phosphoenolpyruvate carboxylase, glucose–6–phosphate,
glucokinase, sterol–regulation element finding protein, acyl coenzyme A oxidase, fatty acid synthase
and uncoupling protein. Testing done on rats with a mixture of cis 9, trans 11 and trans 10, cis 12
CLA had found that the only effected regulatory agents were regulators involved in gluconeogenesis
such as Phosphoenol carboxykinase and transcriptional factors, sterol–regulating element binding
protein–1c and PPAR–y (Choi, Jung, Park, & Song, 2004). The main regulatory effect on insulin
resistance was the effect on ligand PPAR–y, a key regulator in lipid homeostasis. Mixtures of CLA
isomers consisting of cis 9, trans 11 and trans 10,cis 12 effect gene expression of PPARy mRNA in
rats. It was found to have affected the levels of aP2, FATP, ACS and adipoenectin mRNA expression
in adipose tissue. CLA increased These regulatory proteins resulting in an uptake of free fatty acids
into the adipose tissue and decreasing uptake into the muscle tissue. This has been found to improve
muscle insulin

Cardiovascular Disease : The Heart And / Or Blood Vessels
Introduction
Cardiovascular disease is the prevalent and singularly predominant underlying cause of premature
death and disability in the modern world, attributing to 4.35 deaths per year in Europe alone. 1
This general category collectively comprises of all diseases of the heart and/or blood vessels
including atherosclerosis, which is a chronic inflammatory disease that manifests in the wall of
arteries 2 causing their narrowing and hardening due to the aggregation of fatty plaque deposits.
More specifically it affects the intimal layer of elastic arteries i.e. the endothelial cell layer
surrounding the central lumen of arteries 3; damage to this layer can be instigated by various
cardiovascular risk factors, these can be lifestyle/individual based, biochemical or physiological and
all commence through a number of damaging pathways, for example, by drastically increasing the
degree of oxidised low–density lipoprotein cholesterol (LDL), escalating levels of reactive oxygen
species (ROS) and other free radicals etc. although the eventual result in any case is the loss of
normal endothelial functioning.
The damaged arterial site gives rise to the formation of ROS and an increase of adhesion molecules
and permeability.
Subsequently leukocyte adhesion to the artery walls occur and increased permeability results in an
influx of lipids (LDL which oxidates in the blood) and other inflammatory cells into the arterial
wall, upon entry the monocytes undergo

The Discovery Of The Pharmacological Class
However, the discovery of the pharmacological class, Statins of which Lipitor and Compound X
belongs, which inhibits HMG CoA reductase, an enzyme which catalyzes the conversion of HMG
CoA to mevalonic acid, an early and rate limiting step in the biosynthesis of cholesterol, has greatly
improved the management of patients of patients with hyperlipidemia (Bertolini et.al.1997).
Lipitor a Statin drug, acts by inhibiting HMG–CoA reductase and are used as adjunct therapy to diet
to reduce the risk of MI, stroke, revascularization procedures, angina , non–fatal MI, fatal and non–
fatal stroke, hospitalization for CHF, reduce elevated total –C, apo B, and TG levels, increase HDL–
C in adult patients with primary hyperlipidemia and mixed dyslipidemia, reduce total –C and LDL–
C in patients with homozygous familial hypercholesterolemia and reduce elevated total –C and apo
B levels in boys and postmenarchal girls 10–17 years of age with heterozygous familial
hypercholesterolemia after failing an adequate trial of diet therapy. (Lipitor. 2012)
Lipitor is available in dose strengths ranging from 10mg to 80 mg with the recommended start dose
being 10 to 20 mg once daily. Patients who require large LDL–C reductions are recommended to
start at 40 mg once daily. Pediatric starting dose should be 10 mg daily with a maximum
recommended dose of 20 mg daily. (Lipitor. 2012)
Certain groups of patients are contraindicated from taking Lipitor. These are patients who have
active liver disease,

Tetrameric Structure Lab Report
How they work
The tetrameric structure of HMGR has two active sites with each one located between two of the
monomers. The part of the active sites that binds to the substrate is predominantly based on one
monomer while that other portion that binds to the cofactor NADPH is located on the other
neighboring monomer.
The reactive pathway for activation involves a reductive cleavage with transfer of two hydrides. The
hydrides are provided by the cofactor NADPH and hence two NADPH are required for every
reaction (Figure 2).
Figure 2: Reaction pathway catalyzed by 3–hydroxy–3–methylglutaryl–coenzyme A reductase
(HMGR or HMG–CoA reductase).
It is also known that the HMGR is a very flexible enzyme when in its three dimensional structure
and ... Show more content on Helpwriting.net ...
Histidine plays a significant role in this activity.
1. A Histidine residue (His–866) acts as an acid catalyst. Moreover, it also provides a proton that is
required by coenzyme A. This enables it to depart from the mechanism of action a leaving group.
2. Lys–691 creates a hydrogen bond to the substrate but also stabilizes the negatively charged
oxygen of the mevaldyl–CoA the linkages of hydrogen bonds and ionic bonds. Probably, this also
affects the formation of the intermediate products and transitions states that lead to their formation.
It is known that these processes also lower the activation energy for the first step of reactions so that
they can occur very easily (Figure 5).
3. An uncharged glutamic acid residue (Glu–559) also functions as an acid catalyst and a proton
donor for the final stage when mevaldehyde is reduced to mevalonate (Figure 6). It is not normal to
have an uncharged glutamic acid residue present in an active site. This is because there is a
neighboring aspartate residue (Asp–767) which affects the pK of the glutamic acid residue making it
neutral. The aspartate residue also helps to stabilize the ionic form of Lys–691 through the hydrogen
bonding network (Figure

Simvastatin
Simvastatin
Introduction
Simvastatin is used to lower the cholesterol level in the blood such as the low–density lipoprotein
(LDL) and triglycerides and to raise the high–density lipoprotein (HDL), It decreases the risk of
heart diseases and helps to prevent the heart attacks and strokes by reducing the amount of
cholesterol that is made by the liver (Raleys.com, 2015). Chemical structure and functional groups
Simvastatin is one of the statins derivatives that is synthesised from a fermentation product of
Aspergillus terreus. The simvastatin is an inactive lactone which is hydrolysed to the β–hydroxyacid
form when it is taken orally. β–hydroxyacid form is an inhibitor of 3–hydroxy–3–methylglutaryl–
coenzyme A(HMG–CoA) reductase. This enzyme ... Show more content on Helpwriting.net ...
The mode of action
Statins are competitive inhibitors HMG–CoA reductase, it has been considered as a first line for the
treatment of hypercholesterolemia. Their mode of action is by mimicking the substrate molecule
HMG–CoA and competes for binding to the HMGCR enzyme. It works by slowing the production
rate of mevalonate which responsible for the production of cholesterol molecule.
Most of the cholesterol synthesis in the body is done by internal mechanism through the liver cells
particularly at night during fasting; it is taken at night to inhibit the cholesterol production. It
maximizes its inhibitory effect and the data shows a significant fall in the LDL and a fall in the total
cholesterol level in the blood.
Simvastatin can have different pharmacological effects from other statins groups due to different
ring structures and chemical side groups such as different affinity toward the receptors, different
rates of connection to liver cells from non–liver cells, different bioavailability and biochemical
metabolism and execration. All these factors affect its half–life which is short (Anon, 2015).
Statins are selective towards the hepatic cells because of their lipophilic properties. It passes through
the membrane towards the cell

Statin Synthesis Lab Report
Introduction Statins are one of the most widely prescribed classes of drugs in the world. The class
consists of several types of statins, which can be categorized as either type 1 or type 2. Type 1 is
where the statin is derived from natural sources, mainly fungal; where as type 2 are synthetically
derived. The main indication for statins is to lower cholesterol, which in turn helps management in
preventing cardiovascular and heart disease (1). Statins have also been hypothesized to prevent or
treat other health conditions such as Alzheimer's disease, osteoporosis, prostate cancer, and
rheumatoid arthritis; however the evidence is still quite low to justify statins being used for anything
other then for the purpose of their cardiac benefits ... Show more content on Helpwriting.net ...
Myotoxicity can also progress to rhabdomyolysis and therefore can be deadly(B). Although this
adverse reaction has been universally acknowledge, the precise mechanism behind the reaction
remains unidentified. A variety of hypothesis have been postulated which include; statin–induced
interruption of glycoprotein synthesis in the muscle membrane, deficiency in chloride channel
activation in the muscle membrane, and increase intracellular calcium concentrations leading to
impared membrane function

Coronary Heart Disease: Article Analysis
Cholesterol is a waxy, fat–like substance that is found in the cells of our body. Cholesterol is
necessary to make hormones, vitamin D and certain substances that helps to digest food. In our
body, cholesterol travels through bloodstream in packages known as 'lipoproteins'. Lipoproteins are
composed of fat (lipid) on the inside and proteins on the outside. However, high blood cholesterol is
harmful for us. High blood cholesterol is responsible for coronary heart disease (coronary artery
disease) which affects the heart. Low–density lipoproteins (LDL) are responsible for heart disease
while the high–density lipoproteins (HDL) does not cause heart disease. Coronary heart disease is a
condition when plaque builds up in the arteries that supplies oxygen to the heart. Plaque is
composed of cholesterol, fat, calcium and few other ... Show more content on Helpwriting.net ...
The article, 'Statins: mechanisms of action and side effects' describes the mechanism in details. The
rate–limiting enzyme in cholesterol synthesis causes a decrease in cellular cholesterol concentration.
As the cholesterol concentration decreases it activates a cellular signaling cascade that peaks during
the activation of sterol regulatory element binding protein (SREBP). SREBP is a transcription factor
which regulates the expression of the gene that encodes for the LDL receptor. When LDL receptor
expression increases, it also increases the uptake of plasma LDL. Hence, it decreases the plasma
LDL cholesterol concentration. Around 70% of the LDL receptors are expressed by hepatocytes, the
rest are expressed by other cell types in the body. There are few clinical uses; they are
hypercholesterolemia, familial hypercholesterolemia with an exception with atorvastatin. The other
clinical uses are coronary atherosclerosis and prophylaxis for coronary atherosclerosis. However,
there are few unfavorable effects and contradictions

A Brief Note On Patients With Coronary Heart Disease : How...
Q# 6. Statins are used to treat patients with coronary heart Disease.
How do statins work and why are they considered
So beneficial for people with heart disease.
Before we consider the role of statins in people with Coronary Heart Disease (CHD), it is important
to understand the pathophysiology of CHD and its impact on people's health. Coronary Heart
disease is a condition in which fatty deposits accumulate in the cells lining the wall of a coronary
artery, therefore obstructing the blood flow. Fatty deposits (called atheromas or plaques) build up
gradually in the coronary arteries (a process called atherosclerosis) and bulge into the arteries,
narrowing them and diminishing the blood supply to the heart muscle (myocardium)(Taylor ... Show
Diet influences the level of cholesterol and is a risk for CHD. Other risk factors include; cigarette
smoking, high blood pressure, obesity, Inactivity, high Triglyceride levels and male
steroids(Charalambos and M, March 10, 2014).
Genetic predisposition is a critical risk factor for CHD. Lowering levels of cholesterol, both total
and LDL has been proven to slow or reverse the progress of Coronary Heart Disease. The
aggressive cholesterol lowering has been demonstrated to save lives, prevent unstable angina and
Myocardial Infarction and decrease Coronary revascularization rates. This has been achieved with
the use of Statins– HMG–CoA Reductase inhibitors. The level of cholesterol production in the body
is balanced and often depends on genetic factors and intake of saturated fats. One of the final steps
of biochemical pathway of cholesterol production/biosynthesis is regulated by enzyme HMG–CoA
Reductase. The inhibition of this enzyme by Statins, results in a significant reduction of Total and
LDL cholesterol. However on a physiological level Statins also stimulate the clearance of LDL
cholesterol via a receptor–mediated mechanism. Statins generally can reduce the Total and LDL
cholesterol by 45– 50%, depending on the potency of the statin and may also increase the HDL
cholesterol by 10–15%(Mani et al., 2014).
As a result of Statin action, it has

Nurse
Medication Sheet Medication/Dose/RouteClassificationGeneric/Trade Name | Action |
ContraindicationAdverse Effects | Nursing Considerations | Acetaminophen/500mg/ By
MouthAntipyretic& Analgesic (nonopioid)Acetaminophen/TylenolCarvedilol/6.25mg/By
MouthAlpha– and beta–adrenergic blocker & AntihypertensiveCarvedilol/CoregDocusate
Sodium/100mg/By MouthLaxative stool softenersDocusate Sodium/ColaceFurosemide/40mg/By
MouthLoop diureticsFurosemide/Lasix | Reduces fever by acting directly on the hypothalamic heat–
regulating center to cause vasodilation and sweating, which helps dissipate heat.Carvedilol causes
vasodilation by blocking the activity of α–blockers, mainly at alpha–1 receptors. It exerts
antihypertensive effect partly by ... Show more content on Helpwriting.net ...
WD.com recommends enquiry into: diet and lifestyle; duration of constipation and whether it is
acute or chronic; all medications taken, whether prescribed over the counter or recreational;
associated symptoms such as bleeding from the rectum, abdominal pain, vomiting. Implementation:
Oral preparations of Colace should be administered on an empty stomach at least one hour apart
from other medications, meals, milk and antacids. It may be given in juice to prevent possible throat
irritation. Six to eight ounces or 180–240 ml of water should be taken with oral preparations. When
administering rectal preparations, beware of forcing past impacted feces. Discontinue the
medication at the first sign of nausea and vomiting, abdominal cramps or rectal
bleeding.http://preventconstipation.methodsofprevention.com/colace–nursing–
considerations/Assessment: Assess fluid status. Monitor daily weight, intake and output ratios,
amount and location of edema, lung sounds, skin turgor, and mucous membranes. Notify health care
professional if thirst, dry mouth, lethargy, weakness, hypotension, or oliguria occurs. Monitor BP
and pulse before and during administration. Monitor frequency of prescription refills to determine
compliance in patients

Zocor And Heart Failure
Zocor is the brand name of simvastatin, developed by an American company called Merck & Co.
Originally, the research was done by a biochemist named Akira Endo in the Sankyo Company. This
drug is now used to treat various lipid disorders and patients at high risk for Coronary Heart Disease
(CHD). When the research first begun, in 1976, Akira Endo took an "isolated factor from the fungus
Penicillium citrium." This was recognized a powerful inhibitor of HMG–CoA reductase and named
Compactin (or Mevastatin). Animal trials began with a dog, a rabbit, a monkey, and a rat. Although
it lowered plasma cholesterol is the dog, rabbit, and monkey–it did not lower them in the rat. This
made some scientist skeptic about the overall effectiveness of the drug. ... Show more content on
Helpwriting.net ...
Some of the major side effects that can come from taking too high of a dosage is myopathy.
Myopathy is when your muscles begin to weaken because they lose their ability to function as well.
Many people also complain about muscle pain, which is a sign of muscle breakdown. Once the
tissues have broken down, your body must eliminate the waste. This waste can overload the
kidneys, which causes much more serious problems. Another side effect is neuropathy. This is
simply a "malfunction in the peripheral nervous system." This can disturb bodily functions such as
the heart beat and your breathing. However, some of the side effects that are meant to occur are
beneficial to the body. Zocor is beneficial in not only lowering LDL levels, but rasing HDL levels.
This is basically to say that is lowers the bad and raises the good. Due to the lowering of LDL, there
is also increased blood flow, this helps to keep the heart muscle

Potential Cardioprotective Effects Other than LDL Lowering
Potential Cardioprotective Effects Other than LDL Lowering
Cardioprotective effect of statins is ascribed by lowering LDL–C and improving the lipid profile as
reflected in plasma cholesterol levels.
Statins and Endothelial Function
Vascular endothelium plays a role in both vasoconstriction and relaxation, while
hypercholesterolemia by modulating arterial tone adversely affects this process. However,
endothelial function is improved by statin therapy due to production of the vasodilator nitric oxide.
Statins and Plaque Stability
The degree of rupture and thrombosis that is caused by plaques is more profound than the stenosis
they cause. Plaque stability is affected by statin in a variety of ways. They inhibit monocyte
infiltration into the artery wall and also inhibit macrophage secretion of matrix metalloproteinases
which degrade extracellular matrix components and thus weaken the fibrous cap of atherosclerotic
plaques in vitro.
Statins also by inhibiting proliferation of smooth muscle cells and enhancing apoptosis modulate the
cellularity of the artery wall.
Statins and Coagulation
The most compelling evidence of a non–lipid–lowering effect of a statin is the rosuvastatin–
mediated reduction in venous thromboembolic events, a prespecified endpoint, in JUPITER. This
trial demonstrated a 43% reduction in venous thromboembolic events in patients treated with
rosuvastatin, 20 mg daily, compared with placebo during a median follow–up period of 1.9 years
(Glynn et al., 2009).

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