Multidrug Resistance-Associated Protein 2
An overview of Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Protein 2 is a protein found in humans encoded by ABCC2 gene. It is also known as canalicular multiseptic organic anion transporter and belongs to the ATP binding cassette subfamily c member 2. ABC Multidrug resistance family of transporters belongs to one of the largest and oldest with members from extant phyla from prokaryotes and is transported to human beings. In medical field, multidrug resistance is widely used to elaborate resistance mechanism that cells have in response to a wide range of chemotherapeutic drugs used in treatment of cancer.
Function of MRP2
MRP2 is an ATP binding cassette of ABC family superfamily. They transport different molecules across intra and extra cellular membranes. ABC genes are classified into a wide range of distinct subfamilies including MDR/TAP, MRP, OAB, GCN20, White and ABC 1. The drug is therefore widely involved in multi drug resistance.
The protein is also highly expressed in the apical part of hepatocyte and operates in biliary transport. It also includes substrates that include different anticancer medications including vinblastine. Therefore, the protein appears to play a major role in resistance in mammalian cells. MRP2 is also expressed on canalicular membrane of proximal renal tubule endothelial cells. In the cells, they carry out excretion of small organic anions.
Following different studies, MRP2 was included into drug resistance family by Susan Cole and Rodger Deeley in 1996. More members were included into the family afterwards and they were considered as canalicular multispecific organic anion transporter following its cloning. Homology is one of the high MRP2 as it is in the case of MRP1, 3 and MRP6. The MRPs also have similar features of TMD0Lo segment. They also play a role in enhancing pump from eukaryotes such as yeast and leishmanial.
MRP2 in mammals also transport methotrexate and appear to function more in the liver, kidney and the gut.
MRP2 Clinical relevance
MRP2 has a major clinical significance in different cases including Iatrogenic Fanconi Syndrome and Dubin-Johnson syndrome. In the latter, several gene mutations have been discovered in patients. Therefore, there is an autosomal recessive abnormality that is characterized by conjugated hyperbilirubinemia.
MRP2 also enhances elimination of wastes from the body. The organic anions are transferred from the blood to endothelial cells by OAT1 transporter. Waste molecules are transferred into lumen of the tubule by the transporter. More drugs are also eliminated from human body by the mechanism. Therefore, the drugs pass through the MRP2 transporter slowly thus, causing a large buildup of anions in cell cytoplasm.
It is therefore imperative to note that there are different drugs that inhibit MRP2 transporter and they easily cause a buildup of different organic anions in renal proximal tubule cells. If the organic anions inhibit mitochondrial DNA synthesis, they can easily cause iatrogenic Fanconi syndrome. One of the MRP2 inhibitors that has been highly associated or linked to kidney disease is the nucleoside phosphonate adefovir. Cidovir and Tenofovir on the other hand have been linked to Fanconi syndrome.
Multidrug resistance associated protein 2 is also very useful in protection against a wide range of toxic elements and compounds. The availability of various ABC transporters offers a solid defense against toxic elements. Therefore, the discovery of MRP 2 and MRP family at large has enhanced the study of MDR tumor cells. This further led into more interest in the roles and functions of MRP family members in normal metabolism.
Issues related to Multidrug Resistance associated protein 2
There are few issues that have been discovered in MRP2 studies including
- Availability of inhibitors and antibodies that cross react with members of the MRP2 family. However, monoclonal antibodies that act against parts that are not conserved can be generated to address the issue.
- Characterization of MRPs, making them organic anion transporters -Therefore, many substrates for the transporters is highly charged and cannot penetrate cell membrane.
- It is also difficult to get MRP2 transfect-ants therefore; more products are being channeled to cell membrane.
- Last but not least, body cells that are selected for drug resistance in many cases, over express multiple transporter genes. The good thing is that there are several inhibitors that have been utilized to solve this issue.
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The Theory of Natural Selection
As part of the evaluation of human life, numerous researchers have deliberated the concept of natural selection as the focus of the origin of species. The concept supports the adaptations of living things because of environmental conditions. It implies that the biological features are established because of environmental changes (Darwin 23). The concept backs the perceived variation as well as separation of species from their descendants leading to contemporary generation that can change in diverse niches. These changes of numerous features are deliberated as an important feature for existence of the creatures. The concept was established by one of the reputed scientist Charles Darwin in his mission to find the source of living creatures. Via significant evaluation of mechanism, natural selection has been practiced as the solitary tool leading to the evolutionary variations (Darwin 45). This research paper will focus on The Theory of Natural Selection.
Darwin in his numerous primary papers (Jan 1837-June 1838), commence working on a number of options to expound the change of species via adaptation. In his (notebooks, 12, 62), Darwin postulates that species might be “Created for a definite time” and via a stipulated time frame they experience extinction as well as substituted by another. He rapidly left behind the idea and commence deliberating analytically on Lamarck’s concept of impact of influence of environment on the creature growth.
He recounts that the environment had an effect on the variation of the living organism as can be depicted by the numerous fossil accumulations that were growing from simple shells to compound ruins at higher degrees. As a result, he implied that creatures ate in constant alteration. Via his traditional philosophies. Charles Darwin demonstrated a clear relation between the broad-minded variation of the creatures as well as the environmental effect (Gibson 34).
In his early version of the origin, he looks at the subject of natural selection via “struggle for existence perspective”. He concentrates on how alterations offer creatures with the necessary benefit to fight for life and survive (Gibson 37). This is evident literally on how plants that are developing in arid and semi-arid regions go on to tussle for their survival for them to get the numerous needs for their development. Creatures, for example canine group, tussle for foodstuffs with each other. This description symbolizes the future anticipated change on the creatures’ morphologies that are propagated to their on-going selection. This kind of tussle is ventured to fit in line with the slide scale that is from the most strong to the least strong creatures (Darwin 46).
For a number of years, Bacteria and other microorganisms have shown to be quite essential in the experimentation of natural selection and evolution researches. One of the reputed scientific uses of the idea is the growth of the resistant antibiotic in majority of the living organisms. In year 1982, penicillin antibiotic was exposed to aid in the war against bacteria. The alteration of nature between the huge numbers in this populace is looked at due to mutation as well as evolution. When the creatures are exposed to penicillin antibiotic, people that have rehabilitated themselves will live while the poor people will be eradicated by the activity of the bacteria.
This existence criteria of the bacteria lets them breed as well as increase to the next family lineage. The second generations are invariably known to be alienated with improved features to have more control as well as less vulnerability to the antibiotic. The broad application of a number of forms of antibiotics has been looked at by most of the clinicians and scientist as the core cause of the microorganisms’ control to most of the improved antibiotics for a number of years. This is the usual example of natural selection in activity which bacteria has progressed to make sure that they make less vulnerable to the activity of the antibiotics (Williams 45).
Male procreative variations have shown to be quite vital in the experimental researches to show the substantiation of natural selection. Malte Anderson 1982, judgmental studies the rich morphology that a number of of the dating males species retain. He learns that a number of these noticeable facets have repeatedly developed to rejoice in quite improved breeding (Darwin 55). In this research, he examines the Euplestes Progne birds that have quite long tail. He looks at these birds had grown to hold long tails to court with many females as well as those that short tail experiences high likelihood of extermination over years.
John Endler (1980), in his research on Male guppies as well learned a high alteration on the intriguing spots on these creatures from numerous 15 generations (Williams 45). These spots aided these creatures to offer a higher breeding opportunity as well as restricted them from seize by their killers as they were eye-catching. This showed how a number of beneficial features could as well restrict the creature in their natural environment an occurrence invariably known “as trade of” as illustrated in guppies’ trade-off between evasion of hunters and attaining fruitful breeding (Auletta 23).
Stephen (1992) in his systematic study identifies that “Darwin did wrestle brilliantly and triumphantly with the problem of adaptation,” expounds how Charles Darwin fought to demonstrate the numerous natural various natural existence organisms. He expounds how the Malthus rule of action worked on yeast by clarifying that when this populace is introduced in bread, they typically utilize the opening to apply the bread nutrients as well as surge in demography.
This is because of the promising status that they are offered an undertaking he termed as hitting the “Malthusian ceiling”. He uncovered that the desirable condition reduces and the creature beings tussling on the problem for instance as nutrients, space, light as well as cohabitation. In reply to their effort, he comprehends that only the creatures with encouraging features for instance authority will be able endure in such situation. This is apparently shows how creatures are logically picked in a specified setting (Williams 46).
Eventually, it is guessed that Darwin’s concept will come to live in the greatest place in each learned persons’ mind worldwide. This is due to the fact that its prevalent authority to entice the public attention as it pushes its chief plan of natural selection. This is anticipated to go on offering a chance for the scientists to show a number of battles that may be taking place with respect to the concept of natural selection (Stackpole 50). This well acknowledged mechanism of natural selection will reveal the unknown problems for instance how assortment will endure in the future. The concept fuses all the biology as well as history of living and non-living organisms into a single fascinating account.
Reasons why the Darwin’s theory is discombobulating
The verity is that Charles Darwin was disapproved by numerous known scientists of the 19th century. The most of them doubted the concept of natural selection as well as called it a sketchy procedure scientists’ have uncovered that Darwin’s concept botched the test of time (Darwin 65). He evidently grows his concept founded on a longer duration yet he fails to show the claims of the issue of the gone days. He solitary utilizes estimations of about 30 to 50 billion in the past years (Stackpole 54). As a result, not being able to show the incidences that may have occurred since memorial. A collective protest that has as well been uncovered in the Darwin’s concept is that life of creatures is a difficult subject matter that takes a fairly longer duration to develop. The thought of natural selection could not be seen as an apparent concept only for a short duration of time he offered (Darwin 46).
The next catastrophe of Charles Darwin’s concept is its incompetence to explain precisely the legacy and natural selection of most of animals. Darwin’s tree of life considers that nearly all animals came from one single kind of life as well as a collective descendant, via this tree, he does not report that God had a unique ancestry for every animal (Stackpole 58). Darwin does not comprehend that a number of creatures get these genes from their host as they live in them.
For example, the DNA from retrovirus typically put into the living animal’s lives and they get the genes as part of their lives. He as well experienced the difficult of not being able to expound the parity that were formed in the remains. Problems that may only be ratified by the new technology, for instance carbon dating (Stackpole 58). As he understood that natural selection might not sound significant to numerous person, thus, he came up with numerous evidences regarding the adaptation of a number of living organism that can be utilized for research these days.
Auletta, Gennaro, Marc Leclerc, and Rafael A. Martínez. Biological Evolution: Facts and Theories : a Critical Appraisal 150 Years After “the Origin of Species”. Roma: Gregorian & Biblical Press, 2011. Print. Pp. 1-234
Darwin, Charles. Charles Darwin’s Natural Selection: Being the Second Part of His Big Species Book Written from 1856 to 1858. Cambridge University Press, 1987. Print. Pp. 1-275
Gibson, Walter. Black Americans: Biological Facts and Fancies. New York: Vantage Press, 1983. Print. Pp. 1-70
Stackpole, Michael A. Natural Selection. New York, N.Y: ROC, 1992. Print. Pp. 3-45
Williams, George C. Adaptation and Natural Selection: A Critique of Some Current Evolutionary Thought. Princeton: Princeton University Press, 2001. Internet resource. Pp. 1-291
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What is zika virus? What are the symptoms of zika virus? How how is zika virus transmitted? How is zika virus diagnosed?
This article is about the zika virus.
Following World Health Organization declaration on zika virus as a global emergency, there has been a great thirst for information about the virus. In this article we are going to see What is zika virus? what are the symptoms of zika virus and how is transmitted? how is zika virus diagnosed?
However more information is expected to come out with time as more research is done. By the time of writing this post, no treatment had been found to eradicate or prevent the virus. The virus has been described by scientists as a threat to unborn children because it may cause microcephaly. It may also lead to brain damage of the unborn child. On adults the symptoms and effects vary from one individual to another.
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What is zika virus? what are the symptoms of zika virus, how is zika virus transmitted? how is zika virus diagnosed?
Free Term Paper: Effects of Long-term Benzodiazepine Use
There are many effects of long-term benzodiazepine use. Benzodiazepine refers to a psychoactive drug that has diazepine ring and benzene ring’s fusion as its central chemical structure. It can also be defined as any drug in the minor tranquilizers’ family that works against convulsions and anxiety in order to give the user muscle relaxation and sedation. Benzodiazepines work in a similar way in the human brain but their durations and potencies in terms of their affinities in the receptor site and actions vary. For this reason, there are benzodiazepines that are more effective than others in treating certain conditions.
Uses of benzodiazepines that may lead to effects of long-term benzodiazepine use
Among the common uses of benzodiazepines include:
- Use of sedative-hypnotics to induce sleep
- Use of anesthesia adjuncts to induce amnesia and sleep
- Anxiety reduction
- Treating panic disorders
- Preventing or treating seizures
- Muscle relaxant
- Alcohol withdrawal
Benzodiazepines belong to a large class of drugs and their development history is long. They were first approved by the FDA during the 1990s. Since these drugs are available generically, they are very affordable. Because they are all listed as the DEA schedule IV controlled substances, they have addiction; diversion and abuse potential- drugs.com.
Common benzodiazepine drugs
The most common benzodiazepine drugs include Alprazolam, Bretazenil, Bentazepam, Brotizolam, Bromazepam, Camezapam, Cinolazepam, Delorazepam, Diazepam, Clonazepam, Zolpidem, Medazepam, Oxazepam, Pinazepam, Pyrazolapam and Tetrazepam- drugs.com.
Common effects of long-term Benzodiazepine use
The effects of persistence use of benzodiazepines vary among people. However some effects are common among users.
Dependence on the drug
This drug though launched initially as a drug that cannot lead to the formation of a habit or addiction has been rapidly appeared in the scenes of illegal drug use. Benzodiazepine abuse is reportedly high among methadone and heroin abusers. Benzodiazepines are also highly abused by individuals who are highly dependent on alcohol. Cases of individuals with dependence problems have been reported although there is a distinctive feature of the dependence on benzodiazepines. People who develop dependence on the drug do not have classic tolerance. This implies that they do not increase their daily dosage of the drug. Usually, this occurs to users who have a dependence history on the other drugs.
Benzodiazepine causes withdrawal symptoms that are similar to those of other tranquilizer or sedative drugs. Delirium and/or grand-mal seizures can occur if a person stops using the drug at once. Eight out of 200 patients that were admitted at the detoxification unit in McKinnon for primarily using benzodiazepine drugs suffered the withdrawal syndrome. Four experienced delirium while others had seizures- http://www.benzo.org.uk/lennane.htm (follow the link for more details). This indicates that as the effects of long-term benzodiazepine use, withdrawal symptoms have a higher risk of causing seizures than that of alcohol.
Seizures and delirium do not occur when benzodiazepine is withdrawn gradually. However, there are other symptoms that the user suffers. They include insomnia, irritability, gastrointestinal disturbances, anxiety and dysphoria. Other specific symptoms that can occur include perceptual distortions and unduly loud sounds. Others include sight distortion, sight misinterpretation, visual hallucinations, depersonalization and unreality feeling. Patients can also experience taste and smell distortions. Paranoid feelings and thoughts can also occur as well as stiffness in different body parts including the face. Myoclonic jerks can also occur as muscular spasms or fasciculation and local tremors. The symptoms can be distressing and unpleasant and achieving normalcy can take time. For more information about benzodiazepine withdrawal syndrome, follow these links-wikipedia.org, addictionsandrecovery.org.
Cognitive impairment is among the most controversial effects of long-term benzodiazepine use. This drug has been reported to cause impairment in different cognitive domains including processing speed, verbal learning and visuospatial ability. Several papers that were published in the 60s and 70s indicated that benzodiazepine caused short term memory, psychomotor and cognitive function problems.
According to these papers, benzodiazepine cause psychomotor performance and cognitive functioning impairments such as vigilance, reaction time, reasoning, accuracy, speed, judgment and arousal. However, the papers showed that this impairment is gradually reversible with some users improving after 6 years though others suffered permanent and semi-permanent impairment- benzo.org.uk.
A study by Gorenstein, Bernik, Pompeia, and Marcourakis (1995) indicated that there was no significant improvement in performance even after abstaining from the use of benzodiazepine for 10 months- sciencedirect.com. Another study, Tata et al (1994) showed that there were significant memory, verbal learning, visuomotor, visuoconceptual and psychomotor abilities impairments among chronic users of benzodiazepine after six months of successful discontinuation- sciencedirect.com.
Physical and mental health effects of long-term benzodiazepine use
Persistent use of benzodiazepine can cause exacerbation or creation of mental and physical health condition that may improve six months after quitting the use of the drug. Such conditions include anxiety and sleep problems. Improvements on physical and mental wellbeing of the user become apparent between three and six months of abstaining from the drug. For instance, there was a study that indicated hypnotic users experienced less severe anxiety and sleep problems six months after withdrawing from the use of benzodiazepine. They experienced improved health and their distress levels had dropped. Hypnotic users who continued their medication did not show improvement in general health, anxiety and insomnia- wikipedia.org.
Research shows that there is an association between long term benzodiazepine use and increased violent, aggressive and impulsive behavior’s risk. 53 percent of people who persistently used benzodiazepine had violent characteristics. 5.3 percent of those on psychotherapy had aggressive or violent behavioral patterns- wikipedia.org. Those using benzodiazepines on daily basis are highly likely to suffer psychotic symptomatology which includes hallucinations and delusions- wikipedia.org.
Continued benzodiazepine use causes immunological disorders. A study conducted on outpatients that were visiting the psychopharmacology department showed that clonazepam and diazepam had long-term impacts though there were temporary immunotoxic impacts on pregnant rats’ fetus. Nevertheless, a high diazepam dose causes permanent immune-suppression in the neonatal rats- wikipedia.org. Further studies have not been conducted to determine the immunotoxic impacts that diazepam has on humans. Nevertheless, high diazepam doses in humans cause a high pneumonia risk on the basis of a study on individuals with tetanus- wikipedia.org.
Suicide and motor vehicle accidents
This is also among the most controversial effects of long-term benzodiazepine use. There is an association of the long-term benzodiazepine use with suicide and motor vehicle accidents. This risk of people driving under the influence of benzodiazepines is high due to the availability of benzodiazepines in generic form. This risk is similar to that of driving under alcohol’s influence though that of alcohol is slightly higher- aafp.org.
Persistent benzodiazepine’s use is also associated with self-harm or suicide. Depressed adolescents are at a higher risk of committing suicide or self-harm while taking benzodiazepine. However, further research is required to determine the extent of similar effects on adults. Due to benzodiazepine dependence, clinical picture deteriorates and this includes deterioration in the social arena causing drug abuse and comorbid alcoholism. Over-dependence on benzodiazepine leads to suicide. Misuse of benzodiazepine increases suicide risk among the drug users. 23 percent of all females and 11 percent of all males who misuse sedative hypnotic tends to commit suicide- wikipedia.org
Hip fracture risk increases among older individuals by about 50 percent due to persistent benzodiazepine use. A study that involved 43,343 participants showed that there was a 2.55 times increase in hip fracture risk among individuals aged 65 years and above who used zolpidem- aafp.org.
Although the effects of long-term benzodiazepine use are underestimated by some people, it is apparent that they are real and severe in some cases. Benzodiazepines increase various risks including the risk of cognitive impairment, drug dependence, withdrawal symptoms as well as physical and mental health problems among others. As such, people should be careful when using benzodiazepines. Effective alternatives which can be considered exist. For instance, antidepressants and psychotherapy can be used to treat anxiety disorders. Anxiety can also be treated using short-term medications that do not cause benzodiazepines’ dependence risk. There are also alternative drugs such as doxepin, ramelteon and trazodone which can be used to treat insomnia without the rebound risk.
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Free Essay: The Main Causes and Types of Ataxia
What is Ataxia?
Ataxia is a condition used to refer to poor or uncontrolled muscle coordination in the body. It can affect motor skills and movement in patients. Most of those who have this disease have no or little control of their movements. This disease affects daily activities such as walking, eye movement, speech, ability to swallow, picking up objects and other voluntary movements.
Ataxia can be hereditary or non-hereditary depending on its cause. Most of the patients who get ataxia suffer from an ataxic gait. This disease can also be an underlying symptom of other ailments affecting the body. The day for ataxia is celebrated every year on 25th September.
What causes Ataxia?
Ataxia can be caused by three main factors:
- Vitamin B12 This when combined with other neurological abnormalities may cause overlapping sensory and cerebellar ataxia.
- Inherited ataxia. This condition can be hereditary and passed on to children from their parents. Depending on the type of ataxia, hereditary ataxia can be in the form of recessive or dominant inheritance. Recessive inheritance ataxia is only passed to the child if both parents carry the faulty gene. An example of this is the Friedrich’s ataxia. For dominant ataxia, the child is at 50% risk of developing ataxic condition if one of their parents has the defective gene. A case in point is the Spinocerebellar ataxia. In some cases inherited ataxia may worsen from one generation to the next and the onset age may become younger with each generation.
- Non-inherited ataxia. In some cases, patients may develop ataxia due to damages of certain important body parts which control motor skills and coordination of muscles. There are circumstances and procedures that may cause ataxia in people who do not have any family history of ataxia. These include: brain tumor, brain surgery, head injury, alcohol abuse, exposure to toxic chemicals, malformation of the cerebellum while the baby is still in the womb, infections such as chicken pox, drug abuse and multiple sclerosis, cerebral palsy, and some other neurological conditions.
What are the types of Ataxia?
There are different types of ataxia. These include:
- Cerebellar ataxia. This is usually caused by dysfunction of the cerebellum which is the part of the brain responsible for coordination and control of motor skills. This type of ataxia is characterized by poor movement, lack of coordination in movement between organs, limbs and muscles. There is also difficulty in movement of the eye as well as comprehending distance and time components.
- Sensory ataxia. This is where the patient loses proprioception which is the ability to sense the neighboring parts of the body especially during coordination or basic movement. Basically such patients have difficulty in moving and also coordination of limbs, pharynx, larynx and eyes.
- Vestibular ataxia. This occurs when the vestibular system is affected. In this case, the patient may experience vertigo, nausea and sometimes vomiting in severe conditions. Patients also experience giddiness and unsteadiness.
While this is not an exhaustive list of the types of ataxia, there are other types of this condition. Each may exhibit similar symptoms like lack of coordination but have a particular distinctive feature of the disease.
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Free Essay: What is Fragile X Syndrome?
Fragile X syndrome is a condition that is genetically transferred and results in developmental disabilities such as cognitive impairment and learning disabilities. Fragile X syndrome occurs when there are mutations or changes in the X chromosome. This happens when the X chromosome fails to produce enough protein that aids in work cells communication and hence leading to overproduction of CCG. It is estimated that 1 in 8000 females are affected by the Fragile X Syndrome in comparison to 1 in 4000 males. Additionally, this genetic problem is likely to have more adverse effects on the males because they have only one X chromosome as compared to the females who by nature have two X Chromosomes.
What are the Symptoms of Fragile X Syndrome?
There are several signs that can tell when a patient has Fragile X Syndrome. This varies for males and females. The common symptoms of this condition in males include:
- Significant intellectual disabilities. Most males who suffer from this condition possess high levels of intellectual disability. This may range between moderate to severe intellectual disability and is sometimes referred to as mental retardation.
- Moderate to severe learning disabilities is common in males
- Long face and large ears
- Large testicles or a condition called macroorchidism during puberty and post puberty periods is experienced
- Double jointed fingers
- Hyper flexible joints
- High arched palate
- Flat feet
- Behavioral conditions such as autism, ADD, social anxiety, poor eye contact, sensory disorders and risk of aggression.
For females the symptoms are not as severe as those experienced by males. They range from:
- Moderate levels of intellectual disability. Only a third of the females affected by this condition experience extreme intellectual disabilities.
- Mild learning disorders
- General anxiety and behavioral disorders
- Milder physical representation of the Fragile X Syndrome features experienced in the males
The reason why most males experience severe symptoms of the Fragile X Syndrome is because males only have one X chromosome as compared to females who have two X chromosomes. In fact, in some rare cases, there are females who do not exhibit any of the above symptoms until a test is carried out or their family members found to have the Fragile X Syndrome.
What is the Treatment for Fragile X Syndrome?
Unfortunately, Fragile X Syndrome is not a curable condition. To date, no drug has been found to cure this condition. Those with this condition therefore have to learn to live with it and minimize its effects. Amongst the major forms of treatment include:
- Physical therapy. This is usually administered for the patients with severe cognitive impairment which hinders movement and coordination. It is done at the early stages so as to ensure the patient is able to move.
- Behavioral therapy. Most of the patients who suffer from Fragile X Syndrome usually exhibit behavioral disorders such as ADD, ADHD, autism and many other anti-social behaviors. These can be controlled through behavioral therapy.
- Pharmaceutical drugs. Pharmaceutical drugs are normally administered in rare cases and for control purposes as opposed to curing the problem. Any drugs administered to such patients must be prescribed by professional doctors.
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Free Essay: Penicillin Binding Protein and how it Works in the Body
Defining penicillin binding proteins
Penicillin binding proteins are a group of proteins found in different organisms that have high affinity for penicillin and bind themselves to penicillin. These proteins are made up of many types of bacteria. They bind themselves in different ways and as such there are both cytoplasmic bound penicillin binding proteins and membrane bound ones.
Penicillin binding proteins are also different in size and scientists state that up to six different types of these proteins can be found in one bacterium strain. These proteins may range anywhere between 40000 to 91000 in molecular weight. Additionally, these proteins in occur in varying numbers for every cell and each protein has a different affinity for penicillin. There are also two different categories of the penicillin binding proteins and these include the high molecular weight and low molecular weight penicillin binding proteins.
The roles of penicillin binding protein
Despite their differences, each penicillin binding protein helps in synthesizing peptidoglycan. Basically peptidoglycan is a major component of bacterial cell walls and the penicillin binding proteins are involved in the final stages of its synthesis. The essence of this is that bacterial walls when synthesized promote growth of cells as well as cell division which eventually leads to reproduction. Synthesis of these bacterial walls also helps in maintenance of the cellular structure in bacteria.
This makes penicillin binding proteins very important in the reproduction and growth of every organism. When these penicillin binding proteins are inhibited, the cell wall experiences irregularities such as elongation, loss of selective permeability, redundant growth, lesions and eventual death. This can interfere with the functioning of the body.
In addition to this, penicillin binding proteins are used in catalyzing several reactions which are triggered by synthesis of peptidoglycan. These include catalyzing synthesis of cross linked peptidoglycan from lipid intermediates. The proteins also catalyze the removal of D-alanine from the peptidoglycan’s precursor.
There has been much debate about the link between penicillin binding proteins and their role in antibiotic and drug resistance in the body. Several researches have been carried out to determine how penicillin binding proteins may become ineffective leading to antibiotic resistance in the body.
When a patient is treated with small doses of penicillin, the drug attacks the bacteria and changes its shapes causing it to elongate and lose turgidity. As the dosage increases, the bacterial cells completely lose integrity and eventually burst. This helps in killing bacteria and fending off the bacterial diseases.
However, there have been cases where penicillin binding proteins have failed to execute their role in binding certain antibiotics effectively. Basically there are three main ways through which the body of the patient may develop resistance. There are cases where the bacteria change the penicillin binding proteins so that even when they perform their functions, they do not bind themselves to the drugs and hence cannot catalyze the reaction necessary to fight off the bacteria.
Another method in which the body may develop resistance is where bacteria develop effective ways of shielding sensitive enzymes from the antibiotics administered. This method may include the bacteria pumping the penicillin bound drugs away from the cell hence evading destruction.
The last and most effective method of penicillin resistance developed by the bacteria is creation of a special enzyme which is called pecillinase or beta-lactamase. This enzyme seeks out the drugs administered and destroys them.
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Free Essay: Rett Syndrome- Causes, Symptoms, Diagnosis and Treatment
What is Rett Syndrome?
Rett Syndrome is a neurodevelopmental disorder which was discovered by and named after an Austrian scientist called Andreas Rett in mid 1960s. It is a rare condition that almost exclusively affects 1 out of 10000-15000 girls around the world. This disorder interferes with growth and may lead to severe motor skills damage as well as intellectual disability.
Rett Syndrome is extremely rare in boys because it mostly affects the X chromosome. In fact, the few number of boys who have this disorder develop complications and die shortly after birth because they do not have two X chromosomes like girls.
This disorder can also occur in certain girls who do not exhibit the symptoms of the disease. In this case, the disorder is referred to as the atypical Rett Syndrome.
What Causes Rett Syndrome?
Even though this disorder is a genetic one, only 1% of the patients have gotten it through hereditary means. The Rett Syndrome is caused by mutation of genes in the X chromosome. This disorder occurs when methyl CpG binding protein 2 or MECP2 becomes mutated. This gene plays a huge role in brain development because it carries instructions responsible for the synthesis of methyl cytosine binding protein 2, which is an important protein for brain development.
Rett Syndrome thus occurs when the MECP2 gene fails to function properly hence producing insufficient amount of protein or abnormally structured forms of protein. This ultimately interferes with brain development.
However, despite the mutation of MECP2 being attributed as the main cause of Rett Syndrome, it is not always the case. Scientists have discovered that in patients with atypical or congenital Rett Syndrome, there could be other causes such as the mutation of FOXG1 and CDKL5 genes. This hypothesis is still being researched and is yet to be concluded.
What are the Symptoms of Rett Syndrome?
While most patients of Rett syndrome are born normally, they experience slowing down of growth and development at a young age. Symptoms often differ with each stage of development and this is why it is difficult to diagnose the disorder early enough. The following are some of the symptoms that may be seen in a girl with Rett Syndrome:
- Slowed growth especially from the 6th month onwards
- Loss of body muscle
- Small head due to slow brain development
- Difficulty in crawling, walking and sitting
- Poor eye contact and concentration in babies as young as six months
- Wringing and rubbing of hands
- Loss of purposeful use of hands
- Lack of interest in toys, people and surroundings
- The child may have a wide berth in their walking gait
- Breathing problems
- Intellectual disability
How can Rett Syndrome be Diagnosed and Treated?
Rett syndrome can only be diagnosed through the symptoms and genetic testing. Unfortunately, there is no known cure for this disorder yet. However, most patients undergo management therapy. This may include a combination of therapies such as:
- Physical therapy to assist in movement
- Occupational therapy to develop essential skills
- Behavioral therapy for the children who develop anti-social behavior
In addition to this, medication may be administered for certain Rett syndrome patients especially those with breathing problems.
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Free Essay: An Overview of the sex Hormone Binding Globulin
Sex hormone binding globulin is a glycoprotein that binds itself to androgen, estrogen and sex hormones. It is also referred to as the sex-steroid binding globulin and is found in all vertebrate living creatures except birds. However, the sex hormone binding globulin does not bind steroid hormones such as cortisol, progesterone or other corticosteroids. These are bound by transcortin.
Structure of the sex hormone binding globulin
The sex hormone binding globulin is mainly produced by the liver. It can also be produced by the uterus, placenta, testes and the brain before being released into the bloodstream. Where the testes produce sex hormone binding globulin, the result is androgen-binding proteins.
There is a specific gene that carries the sex hormone binding globulin and this is found on chromosome 17 and is called the Shbg. Structurally, the sex hormone binding globulin has two identical peptide chains which make it homodimeric. Even though it has the same amino acid sequence androgen binding protein, they have different oligosaccharides are also produced in different parts of the body.
In addition, the sex hormone binding globulin has double laminin domains. These G-like domains form pockets which bind hydrophobic molecules. These pocket like domains contain a serine residue which attracts two different types of steroids at differing intervals. This changes the orientation of the steroids in the domains.
The sex hormone binding globulin also has calcium ion which is necessary for linking two elements of a dimer together. Where part of the peptide chain forming the sex hormone binding globulin is disorganized, a zinc ion is used in orientating it.
The role of sex hormone binding globulin
The sex hormone binding globulin is used in transportation of the sex hormones such as testosterone and estradiol through the blood stream. The sex hormones are attached to the sex hormone binding globulin and transported to the right places. It can also be used in inhibiting or enhancing the production of sex hormones. Inhibition and enhancement depend on the amount of certain substances in the body. For instance, an increase in thyroxine and estrogen can lead to high levels of the sex hormone binding globulin. On the other hand, prolactin, transcortin, insulin, growth hormone and androgens can lower the levels of the sex hormone binding globulin. There are also certain conditions that can trigger decrease or increase in the sex hormone binding globulin.
Conditions such as obesity, hypothyroidism, acromegaly, polycystic ovary syndrome and Cushing’s syndrome can reduce levels of the sex hormone binding globulin. Puberty also reduces these levels with boys experiencing a much lower level of the sex hormone binding globulin as compared to girls. Anorexia nervosa, hyperthyroidism, pregnancy, oral contraceptives, certain drugs and cirrhosis can increase the sex hormone binding globulin levels in the body. There are different effects of high or low levels of the sex hormone binding globulin. For instance people with very low levels of this hormone binding globulin have high risk of getting type 2 diabetes. Tests can always be done to determine the levels in the body.
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Crucial Factors Researcher Must Consider in Choosing Research Design
Research design presents a structure of given scientific work by providing systematic process and directions of the research. The researcher, first and foremost is supposed to note the research method they choose will affect the conclusion and findings of the results. The main objective of the research is to obtain reliable observations that can help in comprehension of the phenomenon.
There are 3 research designs to pick from and these include qualitative and quantitative methods or combination of both. However, the researcher has to consider the kind of information they are looking for and the purpose of the study before they make a decision on which of these methods to use (Andrew & Halcomb, 2009). Advanced practice of nursing employs the two designs to carry out health care research with quantitative methods used in experiments that require cultural and social perspectives in terms of frequencies or trend while the qualitative techniques are used to describe phenomenon. The research designs above are umbrella bodies from which other designs arise.
The researcher is supposed to understand the nature of the phenomenon, whether it is ideal for data collection and whether data collected would be reliable or valid (Walker & SAS Institute, 2010). For example, if the purpose of the research is describing or observing, the researcher can employ descriptive designs like case study, naturalistic survey or observation. In the case where the goal is to predict, they can employ correlation techniques like cross sectional study or case control study.
Another factor worth considering would be just how reliable the information is supposed to be and ethical conduct of study, which at all stages of the research need to be applied (Walker & SAS institute, 2010). For example, an advanced Nursing Practice Researcher is supposed to avoid risks that could harm respondents.
They are supposed to take into consideration costs they will incur with their choice of design and whether there is any current scientific literature and theory on the study subject (Walker & SAS Institute 2010).
Andrew, S., & Halcomb, E. (2009). Mixed methods research for nursing and the health sciences. Chichester, U.K: Wiley-Blackwell Pub.
Walker, G. A., & SAS Institute. (2010). Common statistical methods for clinical research with SAS examples. Cary, N.C: SAS Institute.
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