Prediction Of Selective Serotonin Reuptake Inhibitor...

Prediction Of Selective Serotonin Reuptake Inhibitor...
What is the topic number of your assigned article and the title of the paper?
#5, Title: "Prediction of selective serotonin reuptake inhibitor response using diffusion
weighted
MRI"
Outline of the Main Points to be included in your Poster Presentation of your article
WHY: The purpose of this article was to present findings of a study that analyzed the difference in
serotonin uptake in the brain between patients who remitted to SSRI antidepressants and those who
did not.
WHAT: I hope to learn more about serotonin uptake in the brain (specifically in the amygdala and
hippocampus) and how this relates to depression and its treatment. I also hope to learn how the
researchers analyzed their data and how they decided to analyze it in a certain way based on the
types of data they obtained.
HOW:
1. Skim and outline:
a. What is the overall objective of this investigation? Why was the study undertaken?
The study was performed to reaffirm a previous observation that there is a difference in ability for
serotonin to bind between depressed people who respond to SSRI's and those who don't. The
investigation focuses on the left and right amygdala and hippocampus. FA (fractional anisotropy)
values of SSRI remitters and non
remitters in the hippocampus and amygdala were found by
performing probabilistic tractography using the DW
MRI scan. Probabilistic tractography was
performed using an algorithm that computes probabilistic streamlines through each voxel. The
weighted average FA is
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Compound X As An Inhibitor Of Bromelain
A) Design an experiment to test whether compound X can function as an inhibitor of bromelain. Be
sure to identify any controls that must be included as well as your independent variable. Hypothesis:
If compound X is placed into the test–tube with pineapple and gelatin, then after freezing it results
in a solid; compound X is an inhibitor of bromelain. Firstly acquire three test tubes. All test tubes
will contain gelatin. One of them will contain both pineapple and compound X. Compound X is our
independent variable in this experiment. Another will contain just pineapple and gelatin. The last
one will contain only gelatin, this test tube will be our control group. The next step is to put all the
test tubes in the icebox and wait for the gelatin

The Consequences Of The Discovery Of Pi3k Inhibitors
Since early 1990 the discovery of PI3K inhibitors are under way. There is evidence that the early
compounds namely quercetin, wortmannin and LY294002 could inhibit PI3K pathway. The latter
two compounds were able to rule the research for more than a decade but their high toxicity and
insolubility precludedthem as in vivo pharmacological drugs [Falasca (2010]. Thus, the attention
was again shifted to the discovery of novel inhibitors that could target distinct member in PI3K
signalling pathway. Very few PI3K targeting agents, like everolimus and temsirolimus (mTORC
inhibitors), have been approved and their application in cancer treatment is limited [Polivka and
Janku (2014)]. Different strategies are being implemented with the aim of ... Show more content on
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The compounds SA16 and IB35 were initially designed to target PDK1 and, serendipitously, found
to inhibit also Aurora A. SA16 and IB35 are novel dual inhibitors that could block both PDK1 and
Aurora A, which are activated in several cancers. With the aim of developing efficacious and less
toxic PI3K/mTORC inhibitors, the compounds we tested on a panel of pancreatic cancer cell lines in
dose dependent way demonstrated that both dual PDK1/Aurora A inhibitors SA16 and IB35 are able
to impair cell growth and migration and that they are not toxic at micromolar range to normal
human pancreatic cells human embryonic kidney cells. The two compounds show a very similar
activity but present some different results, such as the activity on cell proliferation in BxPC3 cells
and on cell migration in AsPC–1 and BxPC3 cells. This could be explained by the different
inhibitory profile possessed by SA16 that, as suggested by their in vitro IC50, inhibits with higher
potency Aurora A compared to PDK1 whereas IB35 inhibits PDK1 preferentially. This is confirmed
by the fact that IB35 activity was more prominent on AKT308 than SA16 and, conversely, SA16
showed a more prominent activity towards inhibition of Aurora A T288 phosphorylation (Figure 6).
However, both novel

Corrosion And The Corrosion Of Mild Steel
N–aminophthalimide as synthon for heterocyclic Schiff bases: Efficient utilization as corrosion
inhibitors of mild steel in 0.5 mol.L–1 H2SO4 solution
Mohamed M. Abdelaal [a]*, Y.F. Barakat [a], Hamed A. Y. Derbala [b], Hamdy H. Hassan [b]
[a] Tabbin Institute for Metallurgical Studies, P.O. Box 109 Helwan, Cairo, Egypt.
[b] Chemistry Department, Faculty of Science, Ain Shams University, Abbasiya, Cairo, Egypt,
11566.
*Corresponding author: E–mail address: chemtims@yahoo.com
Abstract
Many Schiff bases, including two novel compounds, were prepared to inhibit the corrosion reactions
of mild steel in acidic medium. Their chemical structures were determined using IR, Mass
spectrometry and 1HNMR spectroscopic analysis. The results showed that the protection of mild
steel, by these Schiff bases, depends on many factors like function group, inhibitor dose and the
temperature of the medium. Thermodynamic adsorption parameters (Kads, ΔGads) of studied
inhibitors were calculated using the Langmuir adsorption isotherm. The presence of iodide ions in
the medium increased the efficiency of these inhibitors. AC impedance spectroscopy was used to
determine the polarization resistance. The scanning electron microscopy (SEM) showed the
corrosion products decreased after using these inhibitors. In addition, the best inhibitor in this study
used to increase corrosion inhibition of treated sample by Electrolytic plasma process (EPP).
Key words: N–aminophthalimide; Schiff bases; Mass

PARP Inhibitor Case Study
existing FDA approved treatment options to treat your condition.7–8 Your only last hope is the drug
PARP inhibitors group of drugs. 7–8 The drug PARP inhibitors work best in patients like you who
have a BRCA gene mutation.7–8 Following chemotherapy, damaged cancer cell uses an enzyme to
repair themselves and PARP inhibitor group of drugs blocks this enzyme thus preventing the repair
of cancer cell and tumor growth.8 However, This drug is under initial stage of testing.7–8 FDA did
not approve this drug yet for the patients to use in the USA. Hence, it is not available in the market
yet. There are few ways by which you can get this drug. I am willing to supervise this drug use if
you get this drug.7
Let me first explain to you how the drug approval process works in the USA. It will help ... Show
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developed to establish efficacy and safety of investigational product on the subject with disease
(100–300 subjects).12 Phase 3 clinical trials are conducted in a large group of subjects with disease
(several hundred to thousands of people) and take 2–5 years to complete.12 Once the sponsor has
sufficient data for efficacy and safety from phase 2/3, sponsor files a new drug application (NDA) to
FDA for market approval.12–13 When NDA submitted by the sponsor, FDA reviews the application
and send this to one of its reviewer group for evaluation which evaluates the accuracy of submitted
data and decides for its market approval/rejection.12
FDA only approves the drug that is considered as safe and effective for human consumption based
on scientific evidence of data.9 The process of approval at FDA level usually takes 12 months.12
FDA reviews the drugs in 60 days (Fast track) that intended to treat serious or lifethreatening
illnesses and the one that is needed medically but not available in the market yet.11–12
The BioMarin, a California based pharmaceutical company is focusing more on enzyme
replacement therapy for rare genetic disease and has been successful so far developing drugs for

PPI Inhibitors
Strategies to Identify PPI Inhibitors
With the newfound understanding of PPIs, there have been increased efforts to further elucidate the
mechanisms of PPIs, and the past decade and a half has seen significant progress in the field (Fig
3).27, 28 Attempts to inhibit PPIs have focused on two main interaction types: orthosteric and
allosteric. Orthosteric interactions refers to competitive inhibition of the PPIs, by binding to one of
the involved proteins and thus blocking the interface. Allosteric interactions act as a mode of non–
competitive inhibition, binding to a secondary site on the protein and bringing about a
conformational change in the protein which prevents interaction. Orthosteric inhibitors will be the
main focus of this review ... Show more content on Helpwriting.net ...
The p53 protein's primary function is to protect an organism against proliferation of cells containing
damaged DNA, this is done in several ways, including cell cycle arrest and apoptosis.43, 44 MDM2
has been shown to be the principal negative regulator of p53, inhibiting its tumour suppressing
abilities and thus leading to tumour propagation. To this end disruption of the MDM2/p53 interface
is an attractive strategy in cancer therapeutics.45, 46 Independently Grasberger and Vassilev both
successfully used HTS of large compound libraries to discover small molecule inhibitors of
MDM2.47, 48 Grasberger's benzodiazepinedione and Vassilev's cis–imidazoline (Nutlin) were both
able to bind to MDM2 at the MDM2/p53 binding region, disrupting the interface and thus blocking
the interaction. Subsequent medicinal chemistry optimisation of the Nutlin molecule class (3)
yielded the drug compound RG7112 (4, Figure 4).49 RG7112 has been subject to several
exploratory human trials showing favourable outcomes, inducing apoptosis and decreasing tumour
proliferation in patients with leukaemia and various other

Accountability As A Structural Inhibitor
Structural inhibitors are a component that works against a change in there are several inhibitors that
effect an organization's ability to function as a highly effective team. Accountability is only one of
the many inhibitors that effect the performance of a team. Often employees feel that are accountable
to their supervisors and management teams when they should feel accountable to their customers.
Unit structure refers to the focus on individual tasks rather than focusing on the efficiency of the
overall process. Responsibility as a common inhibitor discusses the feeling of responsibility at an
individual level when it is more effective for the individuals to be held responsible for their team's
performance. Lastly, planning and controlling

Ultrasound Accelerated Syntheis of Novel Benzimidazole...
Objective: Present research work is carried out for rapid development of some biological active new
heterocyclic moieties. Method: A novel series of 3–substituted–1–[1–(toluene–4–sulfonyl)–1H–
benzoimidazol–2–yl]–propen–1–one (3a–3j) were synthesized by tosylation of benzimidazole
chalcones (2a–2j) using ultrasound in lesser time with higher yields. All the synthesized compounds
were characterized by Elemental analysis, IR spectra, 1H, 13C NMR and Mass spectroscopy. The
newly synthesized compounds were screened for their α–glucosidases and antibacterial activity.
Result: Biological evaluation of the compounds (3a–3j) revealed that most of them are good α–
glucosidases inhibitors and possess significant antimicrobial activity compared to their respective
standards. Discussion: Amongst (3a–3j), compound 3h showed moderate inhibition of glucoamylase
and compound 3j with compelling inhibition of α–amylase. Compound 3g and 3e displayed
excellent antibacterial activity against all tested strains and admirable antifungal activity against
Candida albicans respectively. INTRODUCTION Glycosidases play an essential role in numerous
biological recognition processes and their function or dysfunction has been implicated in a number
of different disease states, leading to an interest in the screening of different glycosidases inhibitors
(Naoki et al., 2000; Terry et al., 2003). α–Glucosidases (EC 3.2.1.20) constitute a group of exo–
acting glycoside hydrolases of diverse specificity that

ACE Inhibitor Personal Statement
"Replace fear of the unknown with curiosity." These words have been the driving force behind who
I am today. Whether it is ordering a new dish at a restaurant, trying on a new outfit, choosing my
high school subjects, or narrowing differential diagnoses; my inquisitive nature has always propelled
me forward.
Being accepted at the Aga Khan University Medical College, Pakistan's premier healthcare
institution, gave me the opportunity to foster this curiosity. Each lecture challenged me to learn a
new concept, be it simple as the mechanism of action of an ACE inhibitor (hint: it's in the name) or
as complex as the intricate course of a particular artery. During my literature searches, I found that
discovering cutting edge therapies for previously incurable diseases are now approved for use has
been a particularly satisfying way to learn.
I started my clinical years with an open mind to every specialty with the goal of finding the specialty
that catered to my attributes of inquisitiveness, diagnostician and thirst for knowledge. Rotating
through Internal Medicine, I realized that this field provided a challenging environment while
fostering lifelong learning. I found that ... Show more content on Helpwriting.net ...
By watching the house staff and attending I have realized that active listening rather than dictated
questioning can often elicit valuable patient information. I clearly remember a young patient who
was admitted to our service with rapidly declining mental status. Upon carefully listening to the
family, we triggered the management protocol for Naegleria fowleri as we found out that the patient
went for a swim in a local river. This was later confirmed by PCR analysis performed on patient's
CSF. I have enjoyed the fact that patients trusted me deeply with their most sensitive information.
Working together with house staff not only helped me manage my patients but also facilitated me to
become a better

The Synthesis Of Most Coagulation Factors And Inhibitors
Liver has many haemostatic functions including the synthesis of most coagulation factors and
inhibitors as well as fibrinolytic factors. The balance between procoagulant and anticoagulant
factors is essential to prevent excessive blood loss from injured vessels and to prevent spontaneous
thrombosis(11).The global effect of liver disease with regard to hemostasis is therefore complex, so
that patients with advanced liver disease can experience severe bleeding or even thrombotic
complications(12).In our study as regards presence of co– morbid factors namely DM and
hypertension, the prevalence of DM and hypertension was higher in PVT group than non–PVT
group, these results match the findings reported by Martinelli et al.(13) who clarified that
hypertension and DM were associated with increased risk of PVT. That finding may be attributed to
the association of dyslipidemia with diabetes and increased risk of atherosclerosis. So patients with
liver cirrhosis and associated with diabetes or hypertension carry the risk for PVT more than
cirrhotics without them. The number of patients who were Smokers and users ofISSN 2320–5407
International Journal of Advanced Research (2015), Volume 3, Issue 12, 1539 – 1548
1545
contraceptive pills were also statistically higher in PVT group than non–PVT group indicating that
these may be factors for PVT development which goes in agreement with Shetty and Ghosh study
(14). These results may be attributed to the hypercoagulability caused

What Is Angiotensin-Converting Enzyme Inhibitors?
Angiotensin–Converting Enzyme Inhibitors (ACE Inhibitors) are a group of drugs that belong to the
antihypertensive drug class. There are currently 10 ACE inhibitors that are available. ACE inhibitors
can be taken either by themselves or can be combined with a calcium channel blocker or a thiazide
diuretic to enhance the treatment This group of drugs is often used as a first line of treatment to treat
both heart failure and hypertension. Some of these drugs include; benazepril (Lotensin), captopril
(Capoten), enalapril (Vasotec), and fosinopril (Monopril) (Lilley, p. 348). The medical diagnosis to
take ACE inhibitors includes hypertension and can be used as an adjunct for heart failure. These
drugs are considered to be the drug of choice ... Show more content on Helpwriting.net ...
All ACE inhibitors cross the placenta (Vallerand, p 164), which can cause injury or death to a fetus
if taken while pregnant. Also if a patient has a baseline potassium level of 5 mEq/L, they may be
recommended not to take ACE inhibitors due to the risk of causing hyperkalemia(Lilley, p. 349).
ACE inhibitors should be used cautiously in those with any renal or hepatic impairment,
hypovolemia, or hyponatremia (Vallerand, p. 165). ACE inhibitors can cause excessive hypotension
when used with diuretics or other antihypertensive drugs. Also, they should be used cautiously when
taking potassium supplements. NSAID's can potentially block the antihypertensive effects of the
ACE inhibitor and should be avoided. Potential food interactions can occur due to food dramatically
decreasing the absorption of certain ACE inhibitors including captopril and meoxipril. These drugs
should be taken at least one hour before meals to ensure proper absorption (Vallerand, p. 165). Some
common side effects that are associated with taking ACE inhibitors include; nonproductive cough,
hypotension, taste disturbances, diarrhea, nausea, and vomiting (Vallerand, p. 165)). Significant
effects they can have on the central nervous system include, headaches, mood and behavior changes,
fatigue and dizziness. More dangerous reactions include angioedema, hyperkalemia, and renal

Proton Pump Inhibitors Research Paper
Proton Pump Inhibitors are all benzimidazole derivatives that control gastric acid secretion by
inhibition of gastric H+,K+ –ATPase, the enzyme responsible for the final step in gastric acid
secretion from the parietal cells. The PPIs are inactive pro drugs that are carried in the bloodstream
to the parietal cells in the gastric mucosa. The pro drugs readily cross the parietal cell membrane in
the cytosol. These drugs are weak bases and therefore have a high affinity for acidic environments.
They diffuse across the secretory membrane on the parietal cell into the extracellular secretory
canaliculus, the site of active proton pump. Under this acidic conditions the prodrugs are converted
to their active form, which irreversibily binds the proton pump, inhibiting acid secretions. Since the'
active principles ' forms at a low pH it concentrates selectively in the acidic enviorment of the
proton pump and results in extremely effective inhibition of acid secretion.The different
PPIs(Omeprazole,Esomeprazole,Lanzoprazole, Pantoprazole and Rabeprazole ) bind to different
sites on the proton pump, which may explain their differences in potency on a milligram per
milligram basis. PPIs require an enteric coating to ... Show more content on Helpwriting.net ...
The apparent half–life is approximately 48h.This prolong duration of action allows once –daily
dosing of PPIs, although twice– daily dosing is recommended in some cases of erosive oesophagitis
or Barrett's oesophagus when a sustained gastric pH of greater than 4.0 is required. All PPIs are
most effective if taken about 30min before a meal as they inhibit only actively secreting proton
pumps. Meals are the main stimulus to proton pump activity. The optimal dosing time is 30–60min
before the first meal of the

Selective Serotonin Reuptake Inhibitors ( Ssris )
Selective serotonin reuptake inhibitors (SSRIs) have been prescribed by physicians for many years
now. One reason SSRIs are so popular is because of the many mental disorders they can be used for
such as anxiety, depression, obsessive–compulsive disorder (OCD), phobias, and many more
(Weitzel & Jiwanlal, 2001). The four major types of SSRIs that are most commonly used by people
with mental disorders are fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and citalopram
hydrobromide (Celexa); SSRIs work on the brain by acting on the reuptake pathway of serotonin
(Stone, 2010). There are some advantages for taking SSRIs. One advantage is that SSRIs have fewer
side effects than most of the other antidepressant medications such as monoamine oxidase inhibitors
(MAOIs) and tricyclics (Weitzel & Jiwanlal, 2001). Another advantage is that SSRIs have less of a
risk of toxicity in overdose (Lane, Baldwin, & Preskorn, 1995). SSRIs are better tolerated than
tricyclic antidepressant medication because they cause less sedation and problematic anticholinergic
effects. There are also reports indicating that SSRIs have fewer negative effects on the
cardiovascular system than tricyclic antidepressants (Edwards, 1992). Furthermore, some
psychiatrists believe that SSRIs are an important advancement in treating mental disorders
(Edwards, 1992). One article has found evidence that SSRIs can possibly help patients with
recovery after a stroke, regardless of if they did or did not have

Synthesis Of Pi3k Inhibitors
To start with, the synthesis of class I and class III phosphoinositide 3–kinase inhibitors has become a
much–needed research process. Creating and modifying the PI3K inhibitors through the addition
and elimination of organic functional groups or amino acids has allowed scientists to find the best
way in attacking the irregularities formed in the body. Plenty of class I PI3K inhibitors– like those
seen in Figure 3– have been identified and modified for therapeutic means. For example, GDC–
0941 and BKM–120 are both inhibitors that are being considered as possible clinical trial candidates
[2]. Other inhibitors have also been developed for specific PI3K isoforms which helps to highlight
the usefulness of the PI3K pathways [2]. To get a better ... Show more content on Helpwriting.net ...
In the studies being done, scientists realized that the BKM–120 inhibitor not only affects the
PI3K/PKB/mTOR pathway, but the microtubule synthesis pathway, as well [5]. This dual activity
found in the BMK–120 inhibitor was due to the structure of the inhibitor; Figure 5 illustrates how
these two functions are possible (a) and what the ratio of microtubule inhibition and PI3K inhibition
are in the cell (b) [5]. Through extensive studies on the BMK–120 inhibitor and other similar
compound structures, researchers, like Bohancker et al., have been able to identify key structural
components for the two activities. The Bohancker et al. found that additional nitrogen in the core of
the molecule could help remove the tubulin inhibition, as well as, less symmetry in the BMK–120
overall structure [5]. In general, the research being done in these two examples, and the many other
inhibitor synthesis experiments, show how the creation and modification of the phosphoinositide 3–
kinases inhibitors is a huge part PI3K studies. From these developments, scientists can get a better
sense of how the inhibitors will work in cells and treating diseases. Though the synthesis of
phosphoinositide 3–kinase inhibitors is necessary for advancements in this field, research on how
efficient and effective these inhibitors are is just as imperative. Many assays have been developed to
study the effectiveness of PI3Ks– mainly through the quantifying of kinase

Potential Health Risks from Inappropriate Prescription of...
Learning Goals
1) Locate where in the renin–angiotensin–aldosterone pathway ACE inhibitors act
2) Identify commonly prescribed antihypertensive medication by primary care physicians
3) List 3 possible side effects from inappropriate ACE inhibitor prescription
4) Suggest possible regulations of ACE inhibitor use for primary care physicians and alternative
treatment plans for patients
Introduction
Cardiac related diseases account for over 56 million annual deaths worldwide.1 Cardiovascular
disease (CVD) is the leading cause of death in economically developed countries and is increasing
in occurrence in developing nations.1 The prevalence of CVD increases with age.1 The mean level
of blood pressure, used to diagnose CVD, is higher in ... Show more content on Helpwriting.net ...
She has been smoking a pack of cigarettes per day for the past 20 years. She has admitted to
occasional alcohol use. She is allergic to the commonly prescribed antibiotic penicillin.
Biochemical Mechanisms of ACE Inhibitors
The renin–angiotensin–aldosterone system (RAAS) is a group of hormones that are produced
sequentially in order to regulate salt–water homeostasis as well as blood pressure.5 The first
enzyme, renin, is produced by the juxtaglomerular cells of the kidney when blood volume is low and
is released into the bloodstream.3,5,6 Renin then catalyzes the conversion of angiotensinogen to
angiotensin I.3,5,6 Angiotensin–converting enzyme (ACE), which is produced in the lungs,
subsequently converts angiotensin I to angiotensin II, a more active enzyme.3,5,6 Angiotensin II has
several functions. The hormone's primary mechanism for increasing blood pressure is through the
stimulation of blood vessel constriction. Furthermore, angiotensin II increases the contractility of the
heart via sympathetic activation. It also stimulates anti–diuretic hormone (ADH) release, which
increases water reabsorption at the collecting ducts, resulting

Proton Pump Inhibitors
According to Proton Pump inhibitors (PPIs) decrease the generation of acid by hindering the
enzyme in the mass of the stomach that produces the acid. Acid is vital for the arrangement of most
ulcers in the esophagus, stomach, and duodenum, and the decrease of acid with PPIs avoids ulcers
and permits any ulcer that exists in the throat, stomach, and duodenum to mend. According to
medicinenet.com (), proton pump inhibitors are used for the prevention and treatment of acid–
related conditions such as: Gastroesophageal reflux disease (GERD) NSAID–associated ulcer
Zollinger–Ellison syndrome Esophageal duodenal and stomach ulcers Ulcers There are many
different drugs that are associated with the use of PPIs such as Lansoprazole (Prevacid, Prevacid IV,
Prevacid 24–hour), Rabeprazole (Aciphex), Omerprazole (Nexium, Nexium IV, Nexium 24–hour),
aspirin and omeprazole (yosprala), omeprazole/sodium bicarbonate (Zegerid, Zegerid OTC), ...
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However, many individuals don't feel the symptoms, or they can manage them. It is best to ask a
pharmacist the possible side effects that come with any medication you take. The most widely
recognized side effects of proton pump inhibitors are nausea, diarrhea, abdominal pain, vomiting,
headache, rash, constipation, fever, and flatulence. The more serious side effects of proton pump
inhibitors (PPIs) are erythema multiforme, serious allergic reactions, reduced liver function,
Stevens–Johnson syndrome, pancreatitis, toxic epidermal necrolysis and reduced kidney function. If
a woman is pregnant, they should not take any prescriptions unless a doctor says that it is ok. A few
prescriptions can hurt the baby. This includes medicines sold over–the–counter, herbs, vitamins, and
supplements. Furthermore, it is very important that a woman who is pregnant informs a doctor that
they are indeed pregnant, currently breastfeeding, or intending to get

Proton Pump Inhibitors
The quantitative article that I chose to critique talks about the use of Proton Pump Inhibitors (PPI) in
elderly patients to reduce the risk of gastrointestinal (GI) injuries on aspirin and/or NSAID users.
The authors of the study did not list their credentials for this reason it's harder to determine the
authors credibility. However, the affiliation of the authors were stated in the study. For the title,
since the researchers also used H2 receptor antagonists on the study for a comparison, I think that
would have been more appropriate if they added the medication classification on the title as well.
The abstract was complete regarding every detail. The background information was presented, along
with the purpose of the study, the method used, the results, and the conclusion. The problem
statement is clearly presented in the introduction of the article, and it convinces the readers on the
importance of the study, especially for the elderly population. The study is very beneficial and
helpful to the nursing profession, because with the increased use of aspirin to prevent and to treat
various diseases, the associated gastrointestinal injuries also tend to increase (Pilotto, et al., 2004).
Therefore, it is important for nurses to know what is effective to prevent the problem
(gastrointestinal injuries) instead of discontinuing the aspirin regimen. ... Show more content on
Helpwriting.net ...
First, the risk of uncomplicated peptic ulcer linked to acute or chronic use of NSAIDS and/or
aspirin. Secondly, the efficacy of anti–secretory treatment with the use of PPI or H2blockers on
these drug induced ulcers (Pilotto, et al., 2004) The brief literature review provided context and
support for the study, along with gaps from previous studies, such as the efficacy of concomitantly
use of anti–ulcers and aspirin to prevent GI injuries in a short term period (Pilotto, et al., 2004). I
could not find any procedures used to protect the participants during the

Selective Serotonin Reuptake Inhibitor ( Ssri )
Escitalopram is a second generation antidepressant; a selective serotonin reuptake inhibitor (SSRI)
that is used in the treatment of major depressive disorder (MDD) and anxiety related disorders. It is
generic for Lexapro and was approved by the FDA in 2012 for adults and children 12 years and
older who suffer from major depressive disorder and adults who have generalized anxiety disorder.
(FDA, 2012). Since its approval, Escitalopram has also been used in the treatment of Obsessive
compulsive disorder, body dysmorphic disorder, and even premenstrual dysphoric disorder. This
review will discuss the overall effectiveness of Escitalopram, the pharmacokinetic factors of the
medication, the mechanism of action, common adverse reactions, pharmacological effects of the
medication, and its efficacy across different populations. The Pharmacokinetics of Escitalopram
While many selective serotonin reuptake inhibitors (SSRI's) are accepted as first line treatments for
depression and anxiety, they differ greatly in their chemical structure and pharmacokinetic profile.
These differences are especially important when selecting the appropriate antidepressant drug for
the client. It is also important to understand the different drug interactions and pharmacological
profiles when considering an SSRI for a patient as well. An initial starting dose of escitalopram is
usually 10 mg/day. It may be necessary to increase dosage after at least one week of treatment to a
maximum dosage of up to 20

Immune Checkpoint Inhibitors
The Mechanism of Immune Checkpoint Inhibitors
Though there are multiple treatment domains within "cancer immunotherapy," a major source of
excitement has been the discovery and the proven efficacy of immune checkpoint inhibitors –
Ipilimumab, Nivolumab, Pembrolizumab. These drugs operate on the basis that our own immune
cells can recognize and eliminate self–cells (and malignant cells), but are usually inhibited from
doing so by specific receptors and ligand complexes. These mechanisms normally serve to maintain
self–tolerance and limit collateral tissue damage during immune responses, but are exploited by
cancers to evade immune effector cells.[2]
Essentially, immune checkpoints occur during the 1) priming/activation and 2) effector phases ...
IRAEs tend to follow a predictable pattern, with rashes and GI toxicity seen early and liver toxicity
or endocrinopathies seen later in the treatment course. [13] Certain IRAEs appear to be specific to
certain cancers, with pneumonitis being more prevalent in lung cancer patients and higher rates of
vitiligo and colitis observed in melanoma patients receiving infusions immune check point
inhibitors.[14] In general, anti–PD–1 antibodies, Nivolumab/Pembrolizumab, are more tolerable
(10–15% rate of grade 3 [severe] and 4 [life–threatening] AEs) compared to Ipilimumab (20–30%
rate of grade 3–4 AEs) and or combination PD–1 + CTLA–4 blockade therapy (55% rate of AEs).
[14] Immune modulators (IMMs) are employed for high grade IRAEs and most patients achieve
control with steroids or infliximab for steroid–refractory toxicity.[3] Fortunately, it has been shown
that treating IRAEs with steroids/IMMs has yet to show any detrimental effect on the efficacy of
immune check point therapy in terms of OS and

The, Escape Proof Hiv Inhibitor
NTRODUCTION
An impermeable, escape–proof HIV inhibitor is yet to be discovered, more so engineered; however
many scientists continue to expand the possibilities of HIV inhibition through renowned cutting
edge research. Retroviral pathogenesis of HIV has been targeted at multiple stages of viral entry,
replication, and release, with the most promising points of drug target being the initial interaction
between the CD4 T–cell and the envelope mediated fusion of the HIV virion with the CD4+ Helper
T–cell. Currently, HIV entry (fusion) inhibitors range from small lectins found in algae, to antibody
based peptides, to elemental nanoparticles, and each targets a specific step, or multiple sequential
steps, in the HIV entry process. Currently, ... Show more content on Helpwriting.net ...
Presently, the predominant virus is HIV–1, and generally when people refer to HIV without
specifying the type of virus they will be referring to HIV–1. The relatively uncommon HIV–2 type
is concentrated in West Africa and is rarely found anywhere else. There are currently over 34 million
cases of this disease reported worldwide.3 This disease is very slow to develop and may not cause
any significant symptoms before it causes damage, as it is seen a person can have an HIV infection
for years before it progresses to AIDS. Usually, people infected with HIV progress to AIDS when
their CD4 cell count falls below 200.
VIRAL LIFE CYCLE
The main steps in the viral life cycle are (i) attachment of the viral gp120 to the CD4 T cell receptor,
(ii) binding of the gp120 to CCR5 or CXCR4 co–receptors and (iii) fusion of the viral and cellular
membranes HIV entry into the cell is mediated by its trimeric envelope (Env) glycoprotein
gp120/gp41 complex and it happens in two major steps. [1, 2, 4] First, the surface subunit gp120
binds to the cell receptor (CD4) and a co receptor (CCR5 or CXCR4). Upon receptor binding, the
gp41 which is originally sheltered by gp 120, undergoes a dramatic transition from its native state
into an extended pre–hair pin intermediate. Then, the transmembrane subunit gp41 inserts its fusion
peptide (FP) into the cell membrane and packs

The Benefits Of Irreversible Enzyme Inhibitors
Enzyme inhibitors are molecules that bind to enzymes to decrease their activity. Many drugs are
enzyme inhibitors because by blocking the enzymes activity it can kill pathogens (shpanskaya and
Melechko, 2008) Enzyme inhibitors assist in altering the catalytic action of an enzyme in order to
slow down or stop catalysis (Worthington biochemical corporation, 2015). Inhabitation can either be
reversible or irreversible. During irreversible inhabitation the inhibitor detaches slowly from its
targeted enzyme as it is tightly bound to the enzyme by covalent or noncovalent bonds. Important
drugs such as penicillin are irreversible inhibitors. The penicillin covalently modifies the enzyme
transpeptidase which prevents synthesis of bacterial cell walls consequently killing off the bacteria
(Biochemistry, 2002)
As opposed to irreversible inhibition, reversible inhibition is a rapid detachment of the enzyme
inhibitor because the inhibitors bind to the enzymes with non–covalent bonds. Unlike irreversible
inhibitors, reversible inhibitors do not have chemical reaction and can be broken down easily by
methods such as dilution (shpanskaya ... Show more content on Helpwriting.net ...
This is a hormone that whose main function is to constrict blood vessels. This constriction increases
the amount of energy needed to pump blood around the body and can cause high blood pressure.
This can be dangerous for the heart if it had been weakened by heart attack. By blocking the
production of Angiotensin II with ACE inhibitors this, in turn prevents constriction and lowers blood
pressure (American Heart Association, 2015). ACE inhibitors also help to stop angiotensin I from
converting into angiotensin II. By doing this there is a reduction in dilation of the blood vessels.
There is also a reduction of the amount of water returned to the blood by the kidneys which
ultimately leads to decreased blood pressure (Kenny,

The Effects Of Selective Serotonin Reuptake Inhibitors
Introduction
Feeling empty, hopeless and pessimistic, overwhelmed with guilt and irritability, a loss of interest in
activities and fatigue, these are all symptoms of being a teenager, or perhaps an indication of a
greater issue; childhood depression (Kazdin, 2006). Childhood depression has estimates of a 1–year
prevalence as high as 2.5% in children and 8.3% in adolescence (Valnuck, Libby, Sills, Giese, &
Allen, 2004). This is a tragic suffering experienced by many youths, but in 1987 there was the
introduction of selective serotonin reuptake inhibitors (SSRI's). At first glance, antidepressants may
seem to be the answer to a parent of a depressed child's prayers, however they are accompanied by a
terrifying potential side effect (Isacsson, Holmgren, & Ahlner, 2005). In 2004 the US FDA issued an
advisory warning stating that antidepressant use in youth patients may be linked to an increase in
suicidal behavior (US Food and Drug Administration, 2004). Following this warning there have
been many studies conducted to examine the validity of this "black box" caution, and mixed
findings have arose. When taking this possibility into consideration, and remembering that not all
pharmacotherapy will result in suicide in adolescence, an important question to evaluate is whether
or not there is sufficient evidence to support the increased prevalence of suicide among adolescence
who use SSRI's, and if this risk is outweighed by the potential benefits for the use of
antidepressants,

Ssri 's For Selective Serotonin Reuptake Inhibitor
SSRI stands for Selective Serotonin Reuptake Inhibitor. These medications are in a class of drugs
called antidepressants. Antidepressants first started being marketed in the late nineteen nineties to
adults for the treatment of depression and anxiety. Studies done during this time showed that SSRI's
had less negative side effects compared to depression medications that were already being used.
Prozac was the first drug in this classification of antidepressants. Today not only are SSRI's used for
the treatment of depression and anxiety but they also are prescribed to treat post–traumatic stress
disorder, and premenstrual dysphoric disorder. When SSRI's first started being prescribed they were
intended for use in adults only but in the early ... Show more content on Helpwriting.net ...
Physical symptoms can include changes in appetite, changes in sleep, vocal outbursts or crying,
difficulty concentrating, fatigue and low energy, and physical complaints such as stomachaches,
headaches. In most cases there tends to be a reduced ability to function during events and activities
at home or with friends, in school, extracurricular activities, and in other hobbies or interests that are
caused by feelings of worthlessness or guilt (Cummings et al., 2014). It is important to note that not
all children have all of these symptoms. Most children will display different symptoms at different
times and in different settings. Although some children may continue to function reasonably well in
structured environments, most kids with significant depression will suffer a noticeable change in
social activities, loss of interest in school and poor academic performance, or a change in
appearance. It is also common that children may also begin using drugs or alcohol, especially if they
are over the age of twelve. Suicide is a very real concern in today's young depressed population
young, it is a fact that children do attempt suicide (Stone, 2014). Many children may do so
impulsively when they are upset or angry. Girls are more likely to attempt suicide, but boys are
more likely to actually kill themselves

ACE Inhibitor
The first line choice in patients with heart failure is Angiotensin–Converting Enzyme Inhibitors
(ACE Inhibitors). ACE inhibitors can help slow progression of heart failure and improve symptoms.
ACE inhibitors block the action of a protein (enzyme) that causes blood vessels to narrow. As a
result, blood vessels relax and widen. This lowers blood pressure and makes it easier for the heart to
pump blood. These medicines also help body release water and sodium, which also helps lower
blood pressure. ACE inhibitors relieve heart failure symptoms, such as fluid retention and edema.
They may help reduce liver disease and prevent readmission to the hospital. Examples of ACE
inhibitors are Captopril, Enalapril, Lisinopril, Quinapril, and Ramipril. ... Show more content on
Helpwriting.net ...
Amidarone extends the action potential refractory period in the heart. Each time electrical signals
are activated by reaching the action potential. They go through a refractory period where they are
decharged and it is much harder to become reactivated again. Amiderone also inhibits the sodium
channel in the heart and slow inward calcium current. Consequently, the conductivity of the
atriventricular is reduced. Amiderone should not be used in a patient with 2nd or 3rd degree heart
block or sick sinus syndrome without a pacemaker. Common side effects of amiderone include
sensitive to sunlight, fatigue, nausea and vomiting, and taste disturbances. Patients who taking
amiderone should be educated about applying sunscreen and minimize exposing to sunlight. Class
IV antiarrhythmic drugs include cardizem and verapamil. The drugs in this class are used to treat
superventricular arrhythmias which include PSVT, atrial fibrillation, and atrial flutter. The primary
action of the drug in class IV is to inhibit or slow down the movement of calcium through calcium
channels. This relaxes the vessels. The relaxed vessels let blood flow more easily through them,
thereby lowering heart rate. The common side effects of class IV drugs include constipation,
bradycardia, heart block, hypotension, dizziness, and peripheral edema.
(Textbook, p

Hiv-1 In Inhibitors Research Paper
The first notable findings in the development process of the successful HIV–1 IN inhibitor is
development of aryl–β–diketo acids. They provided the first proof of concept for HIV–integrase
inhibitors as antiviral agents in the cell based assay. The aryl–diketoacid containing compounds
(DKAs), exemplified by L–731988 are the most developed biological validated inhibitors. Indeed a
member of this class S–1360 was one of the first IN inhibitors to enter into clinical trials. [46, 47]
Although the diketo functionality, which is believed to chelate two magnesium ions [48], is an
intrinsic feature of the DKAs, it is not sufficient for activity. As typified by the above figure which
appears to be the minimum scaffold required for activity, DKAs ... Show more content on
Helpwriting.net ...
Initial structure activity relationship studies were conducted in order to improve the activity against
integrase, focusing in particular on the basic amine. "This effort led to compounds such as
morpholine 5 and tetrahydropyran 6, both showing low nanomolar activity in the enzymatic assay (5
IC50 =0.003 μM; 6 IC50 = 0.002 μM) and good potency in the antiviral cell based assays in low
serum condition (CIC95=0.250 μM 10% FBS). However, a large potency shift was observed in the
presence of 50% NHS for both analogues, which led us to explore other modifications. The simple
acetamide derivative 7 showed a good potency in all assays and limited shift in high serum
conditions. Various acetamide replacements such as sulfonamide 8, urea 9, and sulfamide 10 were
also prepared. While for all these analogues the potency in the enzyme assay was in the nanomolar
range (IC50= 0.007–0.018 μM), in the antiviral cell based assays, the compounds showed a larger
variability in the activity values, ranging from 0.062 to >1.0 μM in low serum conditions. Only 7
retained activity below 1 μM in high serum conditions (CIC95=0.4 and 0.5 μM 50% NHS for 7."
[17] The amide functionality offered the opportunity to explore very rapidly a large series of
fragments by rapid analogue synthesis. It was discovered that the introduction of an oxalamide
moiety on the scaffold resulted in a very potent compound both in the

P-Glycoprotein Inhibitor
P–glycoprotein Inhibitor Improvement: Verapamil
There are plenty of drugs that are targeting P–glycoprotein (p–gp), which is typically located in
intestinal epithelial cells where drugs absorption occurring. The p–gp controls in and out of most of
foreign substrates from the blood stream. It contributes to balancing out the concentration of drugs
in the blood vain through reuptake process, especially efflux pump in this case. Therefore, this
protein has been called as multidrug resistance because it is able to excrete the drugs into the lumen.
Accordingly, the p–gp inhibitor has an important role for the drug bioavailability and transportation.
As the p–gp inhibitor works in the vivo, the reuptake of drug will be decreasing which means
decreasing the ... Show more content on Helpwriting.net ...
Keisuke Yusa and Takashi Tsuruo, AACR[online], 1989, 49, 5002 – 5006
2. Manuel G., Lluis M. MIR, Stephane Orlowski, EJB, 1996, 244, 664 – 673
3. Sean Ekins, et al, ASPET[online], 2002, 61, 974 –

Serotonin Reuptake Inhibitors: An Argumentative Analysis
Doctors also prescribe Selective Serotonin Reuptake Inhibitors(SSRI) to individuals suffering from
depression, but the same ailment can be treated with amino acid supplements. Some examples of
SSRIs are Prozac, Paxil, Zoloft and Celexa. SSRIs increase the amount of serotonin in the synapse
by blocking its reabsorption, helping the symptoms of depression improve. According to the
American Academy of Family Physicians, benzodiazepines lose their therapeutic anti–anxiety effect
after 4 to 6 months of regular use. Dr. White, clinical psychologist and a certified neurotherapist,
compares antidepressants to a foreign chemical. She is completely against the use of SSRIs because
it blocks the reuptake of the serotonin into the neuron. In simple words, ... Show more content on
Helpwriting.net ...
ADHD is a behavioral disorder that includes difficulty paying attention, hyperactivity and
impulsiveness, and the common drugs Adderall and Ritalin are often prescribed for Attention Deficit
Hyperactivity Disorder. The goal of ADHD medication is to increase dopamine levels in the brain
and to help reduce symptoms of hyperactivity, inattentiveness and impulsivity. Dopamine is a
neurotransmitter associated with motivation, pleasure, attention, and movement. CNN reports that "
The Centers for Disease Control and Prevention notes that fewer than 1 in 3 children with ADHD
receive both medication treatment and behavioral therapy"(Drexler). The new research, published as
two reports in the Journal of Clinical Child & Adolescent Psychology, found that children who
began treatment with approaches –– such as instruction in basic social skills, based on a simple, but
specific, system of rewards and consequences –– fared significantly better than those whose
treatment began with a pharmaceutical, even if both treatments were ultimately combined into one
therapy (Drexler). Restructuring and modifying a child's environment can reduce a child's stress and
reduce many of the symptoms associated with ADHD. Behavior management strategies can help a
child make sense of their world so that they can better understand cause–and–effect and be able to
better predict consequences. An emphasis

ACE Inhibitors
ACE, which stands for Angiotensin Converting Enzyme, is an enzyme that is classified as a kinase
II compound (1). ACE inhibitors are antihypertensive agents that work to slow down the activity of
the ACE enzyme. ACE inhibitor medications are used to help patients with high blood pressure as
well as those who are high risk of getting coronary artery disease, post heart attack, kidney disease
and diabetes (2). ACE inhibitors are membrane–bound dipeptidyl carboxypeptidases that regulate
the renin–angiotensin system (RAS) (3). There are two forms of ACE in humans, somatic ACE and
testis ACE, which regulate blood pressure (3). ACE Inhibitors are found in endothelial, epithelial or
neuroepithelial cells as well as the brain (1). The physiological ... Show more content on
Helpwriting.net ...
While captopril is the only ACE inhibitor that contains a sulfhydryl group, fosinopril contains a
phosphate group. The remaining ACE inhibitors are dicarboxyl–containing compounds as seen in
Figure 2. Captopril has duration of 6 to 12 hours, while most other ACE inhibitors last for
approximately 24 hours (2). The oral bioavailability of captopril is 75%; the elimination half–life is
less than 2 hours. Approximately 50% of the dose of captopril is excreted in the urine without any
changes to the structure; the remaining 50% is converted into a disulfide dimer. For enalapril, the
oral bioavailability is 60% and the elimination half–life is 11 hours. The metabolism and elimination
of this form of the drug is done by hydrolyzing the compound to form a more portent compound,
enalaprilat. After, no further metabolism is required and both the enalapril and enalprilat go through
renal excretion (2). Drugs that contain carboxyl groups, like enalapril, are esterified with an alcohol
to make them more lipophilic, increasing absorption. After the drug is absorbed, it is hydrolyzed by
carboyxlesterase and enaliprilat is released. While enalapril is an inactive prodrug, enalprilat is the
active ACE inhibitor metabolite. Lastly, fosinopril has an oral bioavailability of 36% and a half–life
of 12 hours. Fosinopril is hydrolyzed to form fosinoprilat and is eventually excreted in the urine and
bile (2). A comparison of these values can be seen in Table

The Efficacy Of Ck2 Inhibitors Essay
AML xenograft model: For the proposed studies to test the efficacy of CK2 inhibitor in AML, we
have transduced the human AML cell line, U937 and human APML cell line, HL60 with a lentiviral
vector carrying the luciferase gene. The luciferase–producing U937 and HL60 cells were injected
via the tail–vein into NOD.Cg–Rag1 Il2rg/SzJ (NRG) mice. After 3–5 days, engraftment of AML
cells was confirmed by bioluminescence imaging documenting one log increase in quantitative
signal measured by the IVIS Xenogen reader. Pilot results in two animals demonstrate that both
U937 and HL60 luciferase–producing cells successfully established leukemia (Fig 6). Thus, we have
demonstrated the feasibility of the proposed experiments by establishing two luciferase tagged AML
murine xenografts models in which to assess therapeutic efficacy of CX–4945. Experimental
approach: 2.1) Test the therapeutic efficacy of CX–4945 in AML cell line derived murine xenograft
model We will use 4–6 weeks old female, NOD.Cg–Rag1tm1Mom Il2rgtm1Wjl/SzJ (NRG) mice to
create AML xenograft models. Ten mice per treatment group will be injected with 2x106 luciferase
expressing U937 cells via tail vein. After confirming engraftment by using bioluminescence
imaging, treatment with CX4945 will be initiated. Visible signal or one log increase in signal will be
used as indication of engraftment. The treatment group will receive CX4945 at 100mg/ kg via oral
gavage, five days a week for three weeks and the control group will

Class V : Kmt 4 Inhibitors
CLASS V: DPP 4 INHIBITORS
The DPP 4 inhibitors come in the class of incretin based therapies for type 2 diabetes. The incretin
effect is generally blunted in type 2 diabetes patients.16 The two main incretin hormones
responsible for blood glucose regulation are GLP–1 (glucagon like peptide–1) and GIP ( glucose
dependent insulinotropic peptide). These two hormones are secreted when carbohydrates and fats
are consumed and they result in increased glucose dependent insulin secretion or postprandial
insulin release and decreased glucagon secretion. Both of these hormones tend to be rapidly
metabolized in the circulation by the enzyme DPP 4 (dipeptidyl peptidase). Type 2 diabetes mellitus
is characterized by decreased insulin sensitivity and progressive loss of pancreatic beta cell insulin
secretion .The DPP 4 inhibitors block the breakdown of naturally occurring GLP 1 by competitively
inhibiting the binding of GLP 1 to DPP .The DPP 4 inhibitors decrease the acitivity of the enzyme
dipeptidyl peptidase by greater than 80% for up to 24 hours, thereby augmenting the meal related
circulating concentrations of both GLP–1 and GIP.19The duration of effect of GLP 1 is thereby
increased, thus resulting in a reduction in hepatic glucose output and increase in insulin production.
DPP 4 inhibitors currently approved in the US:
Generic name Trade name Dosage Combinations
Sitagliptin Januvia 25 to 100 mg once daily Janumet( Sitagliptin+Metformin)
Saxagliptin Onglyza 2.5 to 5 mg once daily

The Use Of Rggt Inhibitors Doesn 't Exhibit Any Toxicity...
The use of RGGT inhibitors doesn't exhibit any toxicity in mouse models (Taylor et al., 2011). This
is supported by comparison to gunmetal mice that harbour a RGGT mutation leading to 80%
reduction of RGGT function. There are mild dysfunctional phenotypes such as hypopigmentation
and altered platelet synthesis. This suggests that a decreased RGGT activity, such that Rab proteins
would be hypoprenylated, would not be lethal if targeted (Recchi and Seabra, 2012). The decrease in
RGGT activity is only specific to certain tissues, leading to the idea that this mutation does not
affect all Rabs equally (Hume, et al. 2001).
NE10790 is a phosphonocarboxylate analogue of the more potent bisphosphonate risedronate (BP
RIS), and contains a carboxylate group instead of a phosphonate group. NE10790 is a specific
inhibitor of RGGT, whereas BPs are non–specific inhibitors of Rab prenylation. They act on
farnesyl diphosphate synthase to inhibit prenylation of a variety of proteins such as Rho and Ras,
seen in Figure 9 (Gong, Altman and Klein, 2011). The use of BPs in clinical trials has been
successful in decreasing mortality from lytic bone disease in multiple myeloma. There is also
evidence of anti–tumour effects, such as apoptosis and arresting the cell cycle, as well as in other
tumour cell types associated with bone. BPs have also been investigated in vitro on breast and
prostate cancers, as they commonly metastasise to bone. Studies show inhibition of invasion and
adhesion to bone,

Norepinephrine Reuptake Inhibitor Case Study
As a psychiatrist I, Dr. Anna Morgan, feel that the best methods for treating mood and anxiety
disorders follow the biological approach. There are several different forms of medications that I
recommend to my patients that are suffering from a wide variety of disorders. Selective Serotonin
Reuptake Inhibitors (SSRIs) are widely used for depressive symptoms and also work well for
anxiety disorders. SSRIs have fewer side effects that lead to patients discontinuing their use. They
are also safer in the case of an overdose. Potential side effects include gastrointestinal symptoms,
tremors, nervousness, insomnia, daytime sleepiness, and decreased sex drive. Some familiar trade
names include Paxil, Zoloft and Prozac. SSRIs could be recommended for disorders including
PTSD, Social Anxiety Disorder, Panic Disorder, General Anxiety Disorder, Separation Anxiety
Disorder, Obsessive–Compulsive Disorder, and Bipolar ... Show more content on Helpwriting.net ...
Side effects are similar to those of SSRIs. Some familiar trade names are Effexor and Cymbalta.
SNRIs are used in treating Social Anxiety Disorder, Panic Disorder, Generalized Anxiety Disorder,
and Bipolar Disorder. Benzodiazepines are typically used for phobias and General Anxiety
Disorders. It has shown some benefits, although to a lesser extent, for PTSD. Some forms of
Benzodiazepines have been used for treatment of Bipolar Disorder. Side effects can include
drowsiness, dizziness, gastrointestinal symptoms, confusion, grogginess, change in heart rate and
nightmares. Some common trade names are Valium and Xanax. Some additional medications used
for the treatment of mood disorders include anticonvulsants, Monoamine Oxidase Inhibitors
(MOAIs), and Lithium. Each type of medications has their own side effects that need to be

Essay On BACE1 Inhibitors
Introduction: Figure 1: Formation of Aβ due to cleavage of APP by β–secretase. The first generation
inhibitors for BACE1 were peptidomimetics, compounds in which the scissile amide bond has been
replaced with a tetrahedral intermediate isostere, typically a secondary alcohol. However, the earlier
peptidomimetics have proved to be too large, polar and had no CNS availability.10 The second
generation inhibitors were substrates of P–glycoprotein which effluxes compound out of the cell and
leads to poor CNS distribution. While first generations inhibitors such as BI 1181181, failed in
Phase I trials because of low oral bioavailability and low blood–brain barrier penetration, second ...
204 analogs of this hit was screened to find compound 2 which had improved binding affinity
compared to 1 (Kd=15M). BACE1 is an aspartyl protease which has an acid–base catalysis
mechanism. It uses two aspartates to deprotonate a water molecule in the active site, which then
adds to the substrate. The isothiourea functionality of 2 engaged in hydrogen bond donor−acceptor
interactions with the catalytic dyad of BACE1 (Asp32/Asp228). It also interacts with Ile118 and
Gly230 in the S1 region and Gly34 in the S1′ region. For further optimization, the isothiourea was
replaced by an iminoheterocyclic core to get 3. Compound 3 was developed into the highly ligand
efficient diphenyl iminohydantoin lead compound 4. Figure 3: Lead optimization of the hit 1.
Compound 4 was then further modified to gain drug like properties by core ring expansion and
maximizing structural diversity by incorporating a iminopyrimidinone core with a thiopene and a
pyridine to get compound 5. The iminothiadiazine analog of compound 5 was explored to find
compound 7 with better ligand efficiency. Further SAR studies on compound 6 showed that a
fluorophenyl attached to the iminothiadiazine connected a picolinamide with a fluorophenyl
substituents showed improved biochemical activity and ligand

Selective Inos Inhibitor
Specific Aims
We propose to modify the recently discovered natural product terpenoids to develop a selective
iNOS inhibitor with improved in vivo properties.
Specific Aim #1: To confirm and enhance bonding of terpenoids to iNOS. A SILAC experiment will
allow the action of the small molecule on iNOS, eNOS, and nNOS to be confirmed. SAR studies
will then be performed to enhance selectivity towards iNOS and improve pharmacological
properties.
Specific Aim #2: To study the effects of iNOS inhibition on angiogenesis. The development of
vessels from human umbilical stem cells in the presence of either one of our terpenoids, a traditional
iNOS inhibitor, a genetic knockdown, or a control will be studied to determine the effect of iNOS
inhibition ... Show more content on Helpwriting.net ...
Provided the natural product does not simply quench nitric oxide, further testing will be performed.
Alternatively, if the natural product does show activity towards nitric oxide, it will be modified to a
moiety less sensitive to the radical before further testing is performed. To test for the selectivity of
these molecules SILAC testing will be performed. Using the computer dock data from the terpenoid
paper, a bead will be attached to the small molecule near the isopropyl group, which does not seem
to be involved in any major interactions in the active site. This bead placement will need to be
confirmed experimentally by testing the nitric oxide production of cells in the presence of the
compound and the compound with the bead are similar. After the location of bead placement is
determined, one set of cells will be grown with the small molecule in heavy medium and another
control set of cells in regular medium with no compound. After incubation, the proteins that have
attached to the small molecule can be determined through mass spectroscopy will be

Anti Anxiety : Selective Serotonin Reuptake Inhibitors (...
Medication provides long–term or short–term treatment for patients; it is commonly paired with
therapy to help with physical symptoms or help patients relax during sessions and other activities.
There are four major classes of medications used to treat anxiety: selective serotonin reuptake
inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), benzodiazepines, and
tricyclic antidepressants. Anti–anxiety medication slows down the central nervous system, giving
the user a calm and relaxing feeling. Xanax, Valium, and Klonopin are popular anti–anxiety
medications. These types of medication (benzodiazepines) are classified as tranquilizers.
Medications are fast acting and commonly used to alleviate anxiety episodes or panic attacks. The
effects wear off after a certain period of time and taking these medications comes with drawbacks.
More than one in five adults uses at least one of the previously mentioned medication in 2010
(America's State of Mind; Medco). This figure is an increase of 22 percent from statistics collected
ten years earlier. Use of medication is more commonly seen among females. One in ten people in
Iceland take antidepressants daily while in the United States forty percent of people diagnosed with
mental health issues received treatment in the form of medication. Medications treat physical and
psychological symptoms of mental illness, as opposed to therapy which can only treat psychological
symptoms. National Health Service (NHS) UK offers

Azacitidine are DNA Methyltransferase Inhibitors
Azacytidine or 5 AZC
Trade Name : Vidaza
Introduction:
Azacitidine are DNA Methyltransferase inhibitors. Azacitidine being an analog for cytidine gets
integrated into the DNA sequence of the DNMT gene, the gene turns dysfunctional, inhibiting the
DNA methyltransferase enzymes which normally methylate DNA.
Azacitidine is used primarily for the treatment of myelodysplastic syndromes or MDS– a blood
disorder which affects the bone marrow leading to a low or ineffective production of blood cells.
The cancerous overgrowth of a number of immature cells or blasts and the abnormally developed or
dysplastic cells increase, thereby reducing the cell count of normal red blood cells, white blood
cells, and platelets.
Azacitidine as a chemotherapeutic drug (in low doses) prevents the body from making nucleic acids
required for cell growth of the cancerous cells. This stops the growth of cancer cells and leads to cell
death. Azacitidine also appears to help restore normal growth and differentiation (cell specialization)
in the cells of the bone marrow. This betters the bone marrow production of normal blood cells.
Discovery:
Azacitidine was first synthesized by Piskala and Sorm in 1964 [Piskala A, Sorm F. (1964). Collect
Czech Chem. Commun., 29: 2060–2076]. It was developed as a nucleoside antimetabolite
specifically used for the treatment of acute myelogenous leukemia (Cihak, 1974;Sorm et al., 1964).
But studies later revealed that this drug inhibited cell mitosis with high

Medication : Selective Serotonin Reuptake Inhibitors ( Ssri )
Medication is often used for both long–term and short–term treatment; it is commonly paired with
therapy to help with physical symptoms or help patients relax during sessions and other activities.
There are four major classes of medications used to treat anxiety: selective serotonin reuptake
inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), benzodiazepines, and
tricyclic antidepressants. Antianxiety medication is used to slow down the central nervous system,
giving the user a calm and relaxing feeling. Popular antianxiety medication includes Xanax, Valium,
and Klonopin. These types of medication (benzodiazepines) are considered tranquilizers. They are
fast acting and are commonly used during anxiety episodes or panic attacks. The effects wear off
after a certain period of time and taking these medications comes with drawbacks. More than one in
five adults uses at least one of the previously mentioned medication in 2010 (America's State of
Mind; Medco). This figure is an increase of 22 percent from statistics collected ten years earlier. Use
of medication is more commonly seen among females. One in ten people in Iceland take
antidepressants daily while in the United States forty percent of people diagnosed with mental health
issues received treatment in the form of medication. Medications can be used to treat physical and
psychological symptoms of mental illness, as opposed to therapy which can only treat psychological
symptoms. National Health Service

Acetylcholinesterase Enzyme Inhibitors
Acetylcholinesterase enzyme Inhibitors, preventing acetylcholine degredation through inhibition of
Acetylcholinesterase enzyme. That would cause the accumulation of acetylcholine in synaptic cleft
therefore prolong the neurotransmitter action. Acetylcholinesterase enzyme inhibitors action can be
reversible and irreversible. The reversibility or irreversibility of the inhibitory action depends on the
functional group available in the agent.
Carbamates are derived from carbamic acid, the structure activity relation of carbamates are:
X: can be Sulphur (Thiocarbamate) or oxygen
R1 and R2 : Substitute can by alkyl or hydrogen
R3 : mostly should be organic substitution and sometimes metal
Carbamtes has been used as theraputic agents for ... Show more content on Helpwriting.net ...
Mechanism of action of organophosphorus compounds used in pesticides and nerve agents is the
same however, the compounds in pesticides are developed to be more specific on insects than
warm–blooded organisms, such compound are thio forms of OP , while nerve agents contain oxo
form of Op. In addition OP, acetylcholine esterase inhibitors used in insecticides degrades and
hydrolysis rapidly once comes in contact to sunlight, air and soil. However, in case of prolong and
or repeated exposure to the Ops insecticides can be very toxic and may cause the same result as
acute exposure.
After exposing to organophosphorus compounds, prevention of serine aging and release of
phosphate group is a vital step for survival. Hydroxylamine (NH2OH) is a potent nucleophilic
compound which is able to cleave phosphate esters, therefore it helps hydrolyzing phosphorylated
Ach Esterase enzyme. That leads to develop hydroxylamine derivatives such as; oxime and followed
by pralidoxim as a antidote for phosphorylated acetylchilone esterase enzyme. Pralidoxim chloride
is the only known antidote.
The treatment can be in form of parasymatholytics administration; such as

Rust Inhibitors In The Connecticut
Did you realize that living in Connecticut could cause you to come to a violent end? It's true, and for
a reason you may never expect. One would think road salt would help them during the winter to
reduce slippery conditions, but it also has a very horrid opposite effect.
The Connecticut D.O.T. needs to start putting rust inhibitors back into the road salt. The state uses
magnesium chloride to de–ice the roads, which is especially corrosive. Rust inhibitors work by
reducing corrosion by consuming some of the oxygen that that is necessary to cause rust. Some
officials claim that if it gets into streams, it could lower oxygen levels, killing some fish or other
aquatic animal.
The rust inhibitors were taken out of road salt in CT in 2007 when wastewater treatment workers
reported low oxygen levels outside the plant. Nobody knows that rust inhibitors had anything to do
with it. State officials are too quick, in my opinion, to jump to conclusions. The cars in this state,
one of them possibly owned by you, will most likely experience rust in its near future, if it has not
already. ... Show more content on Helpwriting.net ...
The next victim could be your car! I feel a rust inhibitor should be added before the situation
worsens! Cars are not the only victims,

Prediction Of Selective Serotonin Reuptake Inhibitor...

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