A Study on Diseases, Drug Action, and Obesity: Health and Disease

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This report provides a comprehensive overview of several health-related topics. It begins by examining vector-borne diseases, detailing common illnesses like malaria, dengue, and yellow fever, their transmission, and control methods, including traditional and novel approaches such as Wolbachia and gene-limiting chemicals. The report then delves into the mechanisms of drug action, focusing on how drugs interact with receptors and enzymes, highlighting the use of toxins from animals as pharmaceuticals, discussing their advantages and disadvantages, and providing examples like ziconotide and captopril. Finally, the report addresses obesity, exploring its causes, complications, and assessment methods like BMI, along with a brief discussion on the influence of lifestyle and genetics. The report combines scientific explanations, real-world examples, and current research to provide a detailed understanding of these critical health issues.
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Running head: DISEASES, DRUGS, AND COMPLICATIONS 1
Diseases, Drugs and Implications
Student's Name
Institutional Affiliation
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DISEASES, DRUGS, AND COMPLICATIONS 2
Vector-Borne Diseases
Vectors are disease-transmitting parasites such as mosquitoes, tsetse flies, ticks, fleas,
bugs and some snails. These organisms transfer pathogens such as bacteria and viruses from one
organism (termed as carrier) to another. Common vector borne diseases include malaria, plague,
dengue, lyme disease, chikungunya, tularaemia, schistosomiasis, zika, yellow fever, chagas and
others. A study by the World Health Organization (WHO) shows that more than 17% of the
infectious diseases include the vector borne, with an annual death count of more than 700,000
(WHO, 2017). Malaria is the most killer of all of these diseases. It mostly affects infants of under
five years. However, statistics show that dengue fever has been growing faster than any other
vector borne disease.
The population at risk of dengue fever has risen in recent years, surpassing those at risk
from malaria in populated countries. Dengue is spread by female Aedes mosquito which carries
the dengue virus (WHO, 2017). The mosquito sucks blood from an infected human after which
the virus replicates inside it for a period of 88-12 days, called the extrinsic period. After this
period, the virus can be transmitted to another person when the mosquito bites. The most
dangerous fact about this virus is that once the mosquito contacts the virus, it is able to transmit
it to other people for the rest of its lifetime. The virus is of four serotypes, meaning that one can
contract the virus four times (WHO, 2017). Dengue fever can cause a number of diseases such as
subclinical disease, severe bleeding, plasma leakage and organ impairment.
Yellow fever is a viral disease that often causes jaundice. It is also transmitted by
mosquitoes. Some of the symptoms associated with it are fever, headache, jaundice, nausea,
vomiting and muscle pain (WHO, 2017). The disease is prominent it tropical areas such as in
Africa and South America. It is very difficult to successfully diagnose yellow fever especially in
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DISEASES, DRUGS, AND COMPLICATIONS 3
early stages. It is sometimes confused with several other ailments. There is currently no specific
anti-viral drug to cure this mosquito-borne disease (WHO, 2017). However, it can be prevented
by a vaccine. A small amount of the vaccine can lead to a lifetime of immunity.
Chikungunya is another viral infection that is transmitted by infected mosquitoes.
Infected persons may experience some symptoms for example high fever, joint aches, headache
and joint swelling (WHO, 2017). This virus has been found in some parts of Asia, Indian ocean,
Africa,Pacific ocean and Europe.
There are a number of ways of controlling vector borne diseases. Control can be taken
from either the parasite side, intermediate host or from vector control. A number of vaccines
have been developed to curb the spread of these diseases. For instance, Dengvaxia has been in
use for more than three years for improving immunity against dengue fever (WHO, 2017). To
control the vectors, traditional methods such as use of treated bed nets, indoor and outdoor
fumigation, and destruction of vector breeding areas through proper environmental conservation
methods (WHO, 2017). However,a number of issues arise during implementation of these
control methods. During fogging or spraying of houses, the individuals are at risk of being
exposed to the harmful chemicals used. Furthermore, the space sprayed is very limited for
effective vector elimination (WHO, 2017). Efficiency of the methods in use is also of concern.
Other risks like contamination of drinking water may arise. In general, it has been rather difficult
to limit the spread of dengue fever due to reliance of a high public compliance, high cost of
chemicals such as ovitraps and resistance of insecticides by mosquitoes.
Novel methods of dengue control include the use of a bacterium called Wolbachia
pipientis. This drug is used to regulate the spread of dengue by curbing breeding of mosquitoes
with dengue virus. Specifically, when male mosquitoes with Wolbachia mate with female
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DISEASES, DRUGS, AND COMPLICATIONS 4
mosquitoes without it, the female can lay eggs but the eggs wont hatch (WHO, 2017). As long
as a female mosquito has Wolbachia, their offspring would also have Wolbachia. the presents of
the chemical Wolbachia inside the mosquito effectively result in shortening of its lifespan,
priming its immune system and prevents pathogen replication by limiting the cellular resources.
Another method is the introduction of gene limiting chemicals. GM mosquitoes work by
sterilizing male mosquitoes. When these males mate with wild females, the eggs hatched won’t
develop beyond larvae stage hence the population of mosquitoes is effectively limited (WHO,
2017). More males need to be “sterilized” in order to continuously control mosquito population.
2.
Receptors and enzymes have structures that only allow substances which precisely fit into
them to attach. Drugs work by matching themselves into the receptor structures and hence could
control the physiological action by blocking the proteins or mimicking their effects (Harvey,
2014). Other drugs focus on enzymes which regulate chemical reactions. Together with protein
receptors, ion channels and transporters they are commonly referred to as drug targets.
The effectiveness of a drug highly depends on its ease of controlling the target. It is
therefore important to know the structure and behaviour of a target before formulating a drug
(Harvey, 2014). A good drug target is the one that is very active and plays and important role in
a physiological process. It should have a unique structure such that the drug can specifically lock
on it and not other substances (Harvey, 2014). This property also aids in coming up of specific
drugs through computer- aided methods. A good drug should not be toxic as it may bring about
side effects. The intake into the bloodstream should not require complex means; that is, a drug
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DISEASES, DRUGS, AND COMPLICATIONS 5
should be easily absorbed for quick action. It should have uniform capillary distribution and
should be easily removed from the body by simple metabolic actions to avoid accumulation.
It has been discovered that a number of toxins could be used as effective drugs. These
toxins are extracted from animals such as scorpions, spiders, snakes, conus snails, centipedes and
sea anemones (Tibbetts, 2015). Protein toxins from venom are seen to be effective in binding
with receptors. Since these toxins are mainly made up of proteins, they have high binding
affinity to drug targets such as protein receptors. They are more specific since they mimic protein
structures in the targets. They therefore cause minimal side effects. For instance, the drug
ziconotide is obtained from conus snail and it has ability to interrupt the pain signal,most
especially the pain signal on the spinal cord (Tibbetts, 2015). It has mechanisms of action which
involve the potent and the selective calcium channels. Another advantage of toxins is that they
have a wide range of molecular composition therefore they can be used to come up with a
number of drugs. The many toxin components can have different effects and can target many
receptors hence treating a number of ailments. Captopril, for example, is used for hypertension,
heart failure, diabetes and a number of other defects. Venom toxins effect diverse biological
processes hence finding use in a spectrum of treatment areas such as as neurotoxins, hemotoxins,
cardiotoxins, cytotoxins and necrotoxins (Tibbetts, 2015). Furthermore, toxins with a network of
disulphide bridges are very stable.
Some of the disadvantages of toxins in their application as pharmaceuticals include the
tedious and complex process of obtaining these toxins. Their availability is also limited since
most of them are not orally secreted rather they are secreted inside bodies of the animals
(Harvey, 2014). Toxins introduce the risk of immune response as some of them can block
important proteins. Also, the toxins have short half-life in blood. It has been cumbersome to
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DISEASES, DRUGS, AND COMPLICATIONS 6
manufacture drugs from toxins as the process of separating the toxins and limited solubility of
proteins for large scale production.
3.
Malaria is a disease that is caused by a plasmodium which is transmitted to humans
beings by a female mosquito known as the Anopheles mosquito. The life cycle of the parasite is
indirect and is therefore characterized by two host stages that is a definitive host and an
intermediate host with the Anopheles mosquito being an intermediate host and humans as
definitive hosts. When a mosquito infected by malaria bites a human, it releases sporozoites
which are transmitted into the blood of humans.These sporozoites are the ones that infect the
cells of the liver and afterwards mature becoming schizonts. These rupture releasing
merozoites which lead to an infection on the blood cells(red). These parasites in the blood lead
to the disease.
Malaria has several symptoms which include high fever, profuse sweating, bloody stools,
diarrhea, convulsions, headache, nausea, vomiting, abdominal pain, shaking chills and muscle
pain among others. These symptoms can develop within days or weeks after the infection.
The current prevention measures against Malaria include chemoprophylaxis as well as
individual protection against the mosquito bites. Chemoprophylaxis is given to those travellers
who are visiting malaria endemic countries.The drug administered depends on destination of
travel, duration of the exposure to the malaria parasite, resistance of the parasite, the level of the
transmission of the disease,one’s age and if someone is pregnant. In countries that are endemic,
chemoprophylaxis is normally administered to young children as well as the pregnant women.
This will be dependant on the level of the transmission and the seasonality of the transmitted
parasites.
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DISEASES, DRUGS, AND COMPLICATIONS 7
A physician based in German known as Johann Friedrich Meckel was the first one who
saw P. falciparum though he did not know that it was the parasite. He reported the presence of
some black pigment granules from a sample of blood of a patient as well as the spleen of a the
same patient who succumbed to malaria in 1847. An Army physician of french origin, Charles
Louis Alphonse Laveran, in his time at Bône Hospital also identified the same parasite as a
pathogen which causes malaria. This was in 1880.
An understanding of the genetic mechanism that causes a disease can contribute to new
control methods of the parasite or the said disease. Some knowledge of gene structure of the
parasite Plasmodium falciparum and that of the Anopheles gambiae can offer a new perspective
on malaria therapy, the vaccines as well as control of the transmissions by the mosquitos. In a
genetic study of Malaria, an observation was made that Duffy antigen–negative individuals were
resistant to infections of P.vivax. This led to a vaccine against the said P. vivax which is
currently undergoing some trials. These understandings can also solve some questions which are:
how can the infected individuals rid the malaria parasites from their bloodstream? And why
malaria parasites could cause some cerebral complications in one person and not in another
person.
4.
Obesity is a widely spoken subject that has attracted a number of social myths and
scientific explanations. In the movie “Wall-E”, obesity has been associated with eating cultures
as well as inactivity of human race (Stanton et al., 2008). That staying indoors all day without
exercise and eating a lot is the main cause of obesity- a worry for the world. It is true that obesity
can cause a number of complications such as cancer, kidney failure, respiratory disorders,
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DISEASES, DRUGS, AND COMPLICATIONS 8
problems with movement, infertility and reproductive defects, cardiovascular disorders and
psychiatric complications.
Obesity is caused by factors such as the kind of diet and levels physical activity. There
are also genetic causes as well as environmental factors that contribute to high risks of obesity.
This is a condition that is associated more with kind of lifestyle. It is said that one is obese when
their body-mass index is above 30. It is as a result when the body is unable to burn excess fat in
the body. It can therefore be viewed in terms of how much fat is taken in, what effort is put in
exercising to burn the taken-in fat and normal operation of metabolic activities inside the body
that burn fat (Gray et al., 2018). There are some inherited genes that dictates the amount of fat
that the body stores. They also dictate where these fats are stored. Another factor is the eating
habits of an individual. A healthy diet should balance the amounts of sugar, fiber, fat salt, energy
and other minerals. Specifically, the types of fats such as monounsaturated fatty acids,
polyunsaturated acids, trans-fatty acids and saturated fatty acids have different rates of
metabolism (Gray et al., 2018). Those that are hard to be broken down ends up being deposited
in the body.
Its also important to track the energy taken into the body. There must be a balance
between intake and release. When the body is not engaged in energy-requiring activities, it gets
into risk of obesity. As depicted in the movie, it is true that staying glued to television screens,
especially by children, is the explanation of high obesity rates (Stanton et al., 2008). It is also
important to indicate that the type and intensity of exercise engaged in matters in fat-burning.
5.
Introduction
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DISEASES, DRUGS, AND COMPLICATIONS 9
TTF-1 refers to Thyroid transcription factor which is also referred to as thyroid specific
binding protein or NKx2.1.It generally weighs 32.8 kilodaltons i.e. gene encodes a protein and is
present at the site of chromosome 14Q13. TTF-1 is generally exhibited in the region of lung,
diencephalon and thyroid during the process of embryogenesis. The factor contributes a major
role towards lung and thyroid morphogenesis and development during the stage of
embryogenesis. The role of TTF-1 in development of lung cancer in humans is yet to be fully
explored.
Body
Research evidences indicates the progress of cancer is promoted by TTF-1. Cell
proliferation and its regulation result in formation of vessels and is most commonly observed
with adenocarcinoma condition which results in increase the cell proliferation rate.TTF-1 is most
often associated with adenocarcinoma in comparison with other carcinoma types. It is rarely
associated with small cell lung cancer as compared to squamous type of lung cancer. The role of
prognosis with reference to TTF-1 for lung cancer survival was assessed in several research
studies. It indicated incorporation of non-small lung cancer carcinoma at different stages of local
and regional areas. Results obtained showed conflict and did not provide conclusive evidences.
TTF-1 is generally referred to as a vital prognostic factor with reference to survival in
non-small lung cancer. There are several research evidences with references to prognostic studies
associated with lung cancer and all these studies mainly focused on identification of biological
parameters. The influence was mainly disease stage and strategy for therapeutics. TTF-1 is
considered as a critical marker and is mainly used in clinical research in order to differentiate
between adenocarcinoma related with lung and metastatic type of lung adenocarcinoma.
Research studies also confirm that TTF-1 is also found to express in squamous carcinoma
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DISEASES, DRUGS, AND COMPLICATIONS 10
associated with lungs. The role and function of TTF-1 associated with lungs is still not clear but
several research studies indicate different explanations. Some of the studies indicate detrimental
effects associated with TTF-1 which include both negative and positive tumors and other studies
indicate with the help of literature that a meta-analysis is required to be carried out. Results from
meta-analysis studies indicate a Positive for TTF-1 which is integrated with non-small lung
cancer cells survival. This is most commonly explained during the early disease stages. The
positiveness of TTF-1 is mainly related with better rate of survival in non-small lung cell
carcinoma and it is specific to local and early stages especially with adenocarcinoma.
TTF-1 is considered as a major transcription factor for specific genes associated with
tissues. Over expression of TTF-1 is associated with patient prognosis. The reason for
prognostic ability is mainly associated with epidermal growth factor receptor as it indicates
positive correlation between mutations of EGFR and expression of TTF-1. It plays a major role
in functioning of respiratory cells present at terminal end by means of controlling proteins
associated with surface. The functioning of TTF-1 will extend further with reference to adults as
it plays a major role in functioning of cells present at respiratory region and it is considered as a
lineage marker which is used to carry out diagnosis specifically for lung adenocarcinoma type
and small cell cancer type.
In conclusion, TTF-1 expression showed positive response for stage 1 lung
adenocarcinoma type. However, there are limitations such as size of sample and status of
mutation. The survival of lung cancer patients is found to increase at initial stages associated
with expression of TTF-1 and is considered as a better prognostic factor for patients suffering
from lung cancer. The impact of prognosis with reference to expression of TTF-1 will depend on
EFGR mutation status in patients suffering from lung adenocarcinoma.
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DISEASES, DRUGS, AND COMPLICATIONS 11
6.
Western blot test is generally employed in the detection of specific proteins which are
contained in a sample and separate them. The SDS-PAGE(polyacrylamide gel electrophoresis) is
used in the separation of the proteins in the said sample. The proteins that are separated are
afterwards transferred to a matrix which is generally either nitrocellulose or the PVDF
membrane.These have the antibodies specific to the protein that is targeted.
The steps that are involved in the process of the western blot and the detection assay
include transfering, blocking,the primary antibody incubation, the secondary antibody incubation
and the protein detection as well as analysis. In the process of transferring,the proteins are
transfered from the polyacrylamide gel to the membrane with a high intensity electric field which
is produced by an electrode plate that is in parallel with a sandwich. The blocking is important
because the sites that did not react are blocked and this reduces the amount of the nonspecific
binding of the proteins which occurs in the steps that follow and this happens in the assay in the
presence of nonionic detergent or inert protein. In the incubation of primary antibodies process,
the antibody is bound to the proteinthat is targeted which is found on the membrane. Rinsing of
the membrane is then done to remove the antibody that did not bind.Exposing it to a secondary
antibody is the following step. The antibody(secondary) then binds to the antibody(primary)
which will have reacted with the target protein. In protein detection, a substrate is used in the
reaction of the enzyme which is bound to the antibody(secondary). This generates a substance
that is colored otherwise known as a visible protein band. The levels of proteins in the cells are
evaluated using methods such as densitometry and also locating the protein bands. The sample is
then analyzed and the specific proteins in the sample are detected.
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DISEASES, DRUGS, AND COMPLICATIONS 12
7.
GADPH refers to Glyceraldehyde 3-phosphate dehydrogenase. It is a key enzyme in
glycosis. GADPH is also a housekeeping protein and most tissues have high amounts of it that is
why it is used in Western blotting as a loading control.When performing western blotting, a
control protein is needed as it indicates the proper transfer of the proteins to the membrane.
8.
Molecular weight markers are mainly used to estimate the molecule size that run on gel
during the process of electrophoresis (Magdeldin et.al,2014). Western blotting bands show in
one lane with intense or with low intense levels but the loads present can have identical amounts
of lysate on gel for both patient and healthy individual.That is why the lanes for both the patient
and healthy individual look identical. SDS-PAGE separates proteins by mass. The Sodium
dodecyl sulphate acts as a detergent that is ionic and binds to the proteins. This results in
formation of negatively charged particles (Mishra, Tiwari & Gomes, 2017). Application of a
current will result in proteins getting bound to a SDS-PAGE present in a sample. They then
migrate towards the gel and from there they move further towards the positively charged
electrode.
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DISEASES, DRUGS, AND COMPLICATIONS 13
References
Gray, C. L., Messer, L. C., Rappazzo, K. M., Jagai, J. S., Grabich, S. C., & Lobdell, D. T.
(2018). The association between physical inactivity and obesity is modified by five
domains of environmental quality in U.S. adults: A cross-sectional study. PloS One,
13(8), e0203301. Doi: https://dx.doi.org/10.1371%2Fjournal.pone.0203301
Harvey, A. L. (2014). Toxins and drug discovery. Toxicon, 92(15), 193-200.
https://doi.org/10.1016/j.toxicon.2014.10.020
Stanton, A., Morris, J., Lasseter, J., Reardon, J., Docter, P., Newman, T., Eggleston, R.,..(2008).
WALL-E. Buena Vista Home Entertainment.
Tibbetts, J. H. (2015). Turning Toxins into Treatments: Researchers use new tools to identify
therapeutic ingredients in animal venom. BioScience, 65(10), 957-962.
https://doi.org/10.1093/biosci/biv123
World Health Organization. (2017, October 31). Vector-borne diseases. Who.org. Retrieved from
https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases
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