The ‘Bacteria’s Movie Out’: cas9 CRISPR in genomic encoding

Rafat Shahriar Islam

DNA (Deoxyribonucleic acid), the genetic blueprint of every living creature including diverse classes of microorganisms has its sole act to carry the inheritance in sequences of generation. A bacteria, much like a prokaryotic tiny microbe, has been used by the researchers of Harvard Medical School after harnessing its DNA  being used as a synthetic raw material to store information digitally in an In vitro(Outside of living cells) process.

CRISPR (Clustered regularly interspaced short palindromic repeats), a prokaryotic DNA of Bacterial genome provides the bacterial genome an acquired immunity against viral phage or plasmid. In a palindromic repeat, having same nucleotide sequence in both directions, there are repeated short spacer DNA segments along with small clusters of cas genes are located next to CRISPR sequences (CRISPR/Cas system).  For clear understanding, in CRISPR/Cas9 system, Cas9 nuclease complexes with a synthetic guide RNA (gRNA) cut the genome of a cell, allowing the introduction of genes or snipping out of them.

The researchers at Harvard Medical School described through ‘Cryo-electron microscopy’ that the CRISPR complex loads target DNA and make it ready for cutting by the Cas3 enzyme. These structures reveal a process with multiple layers of error detection preventing unintended genomic damage. Discovered not so many years ago, CRISPR-Cas is an adaptive defense mechanism against viral invaders. In this process, bacteria capturing portions of viral DNA, which are then integrated into its genome producing short RNA sequences known as crRNA (CRISPR RNA). These small crRNA parts are a tool for detecting “enemy” presence.

Acting like a barcode, crRNA complexes with the CRISPR family of enzymes, which together perform the function of ‘border guards’ that move around the bacteria and checks for foreign code. If crRNA/CRISPR complexes encounter genetic material that matches its crRNA, they slice down that DNA to make it harmless. Likewise, as previously told, CRISPR/Cas9 can be programmed with synthetic RNA (gRNA) in order to cut genomes at a specific locus, allowing researchers to edit genes easier than ever.

Now the question may emerge on what if by using CRISPR/Cas system, large populations of the bacterial genome can be used as a biological hard drive that can record information as megabytes/gigabytes like external drives and that can be accessed anytime? Such a breathtaking approach by the researchers of the Wyss Institute of Harvard Medical School have already created an outstanding dimension after engineering a new memory-recording device via genome of bacteria population in a chronological fashion.

The first approach began recently in 2016 by an Engineering team led by George Church from Harvard Medical School and the Wyss Institute to build the first molecular recorder based on CRISPR system where bacteria are encoded bits of information within their DNA to produce a memory of that information within the genome as a cellular model. The information is stored as an array of sequences in the CRISPR locus which whenever required can be recalled and can be used to reconstruct a still or moving image!

In July 12, 2016, in Nature, the same team showed the first of its kind approach to a whole new level showing that they were able to encode a digitized image of a galloping horse in bacterial living cells which were one of the first ever reminiscent hand-made paintings crafted on the cave wall by ancient humans. It was of one of the first motion pictures ever made by the team successfully!

To explain briefly, the CRISPR system captures viral DNA molecules and generates short, so-called ‘spacer’ sequences from them that are added as new elements continuously in a growing sequence located in the CRISPR locus of bacterial genomes. The CRISPR-Cas9 protein constantly resorts to this memory to destroy the same viruses if relapsed.

In this study, it was shown that two proteins of the CRISPR system, cas1, and cas2 that was engineered into a molecular recording tool enabling the scaled-up potential for acquiring memories in the genome. Natural tissue environments can also be recorded presenting a way to cure different types of living cells where they synthetically create memory hotspots in their genomes.

On much larger scales, the team worked on both still and moving images because they represent clearly defined data were developing this concept for making a movie offers the chance to have bacteria gather information frame-wise over time.

The study’s first author Shipman described that they had translated the digital information contained in each pixel of an image into a DNA code that also incorporated spacers making each frame a collection of these. The author further added that later they had provided spacer collections for each consecutive frame chronologically to a population of bacteria using Cas1/Cas2 activity, adding them to the CRISPR arrays in bacterial genomes after they had retrieved all arrays by DNA sequencing. Finally, a reconstructed image using all frames of the galloping horse movie was screened in a sequential order of appearance.

Another researcher Min Luo, working on CRISPR/cas system stated that these steps must occur in a precise order. Luo further replied that evolutionarily, this mechanism has to ensure that this complex must degrade only invading viral DNA.

In future, the team will focus on inventing a new molecular recorder to memorize biological information in other types of the cell too. Donald Ingber, Wyss founding director addressed this as the ‘groundbreaking technology’ in the field of ‘DNA-based information storage’ aiding the living cells to record, archive and propagate that information to study dynamic biological processes in an in vivo (inside the living body) way which is also another example of ‘bio-inspired engineering’.

In fine, Shipman forecast about their invention, “One day, we may be able to follow all the developmental decisions that a differentiating neuron is taking from an early stem cell to a highly specialized type of cell in the brain, leading to a better understanding of how basic biological and developmental processes are choreographed”.

Rafat Shahriar Islam, is a graduate from Department of Pharmacy, East West University.  He can be reached at rafat.islam46@gmail.com

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Producer of “Werewolf Human” – Hypertrichosis

Bulbul Ahmed

We all know about X-MEN, a very popular Marvel Comics and also a movie series. There is a superhero named Henry Philip (known as Hank; The Beast) who has lots of fur on his face and all the body skin. At the extensive level, hypertrichosis patient becomes similar looking to that superhero but the sad news is that patient doesn’t have any super natural power.

Hypertrichosis is often mistakenly classified as hirsutism. Hirsutism is just a male type hair growth in the female. It can be caused by Increased production of androgens and androstenedione or the increased sensitivity of the skin to them. But hypertrichosis is excessive body hair growth at appropriate sites compared to other persons of the same sex, age, and ethnicity. Not androgen-related. Extensive cases of hypertrichosis have informally been called werewolf syndrome. There are mainly two types of hypertrichosis: Congenital and Acquired. But classification can also be based on the age of onset and site of growth.

Congenital hyperchosis is always present when birth but it is rare. It is generally caused by genetic mutation. But acquired hypertrichosis appears after birth. The multiple causes include the side effects of drugs, associations with cancer, and possible links with eating disorders. There are several types of congenital hyperchosis. In congenital lanuginose hyperchosis infant completely covered with a thin lanugo hair and remains after birth but palms of the hands, soles of the feet, and mucous membranes are not affected. Acquired lanuginose hyperchosis characterized by rapid growth of lanugo hair. Palms and soles are unaffected. The excess hair is commonly referred to as malignant down.This hair is very fine and unpigmented. In Congenital generalized hypertrichosis, hair growth is more prominent on the face, ears, and shoulders. The palms, soles, and mucous membranes are not affected. Acquired generalized hypertrichosis commonly affects the cheeks, upper lip, and chin and rarely affects the forearms and legs. It is mostly vellus hair and rarely lanugo. In terminal hypertrichosis, terminal hair covers the entire body. It also causes gingival hyperplasia. Gingival hyperplasia is an increase in the size of the gingiva or gums. This hypertrichosis is most responsible for “werewolf syndrome” for its thick, dark hair. Nevoid hypertrichosis may be present at birth or appear later. In few cases, more than one patch of hair is present.

The cause of hypertrichosis is unknown. Congenital hypertrichosis is believed to be a genetic disorder that is inherited or occurs as a result of spontaneous mutation. It also caused by reactivation of genes that cause hair growth. The genes which caused extensive hair growth in early man have “shut down” during the course of evolution. By a mistake that still has no known cause, these hair-growth genes “turn on” while a baby is still in the womb.

Acquired hypertrichosis lanuginosa sometimes occurs in people who at a later stage are diagnosed with a cancer of some form. This hair growth, also known as malignant down, is often confined to the face with long fine silky hair noticeable on the nose and eyelids, sites that are normally hairless. It is not known why cancer causes this excessive hair growth.

Treatment options are limited and depend on the patient characteristics and area and amount of hair growth. Some short term treatments that can be used is applying shaving but the hair will grow back, unfortunately. The currently available treatment methods include cosmetic procedures (bleaching, trimming, shaving, plucking, waxing, chemical depilatories, and electrosurgical epilation), and hair removal using light sources and lasers.Laser-assisted hair removal is the most efficient method of long-term hair removal currently available. A novel treatment for slowing excessive hair growth is topical eflornithine, an inhibitor of the enzyme ornithine decarboxylase present in hair follicles that are important in hair growth.

Although this disease rarely occurs in our country, the patient must be neglected by various ways in social. The main thing which is needed to the patient is self-satisfaction.   

Bulbul Ahmed is an undergrad student of Department of Pharmacy East West University, Dhaka, Bangladesh. He can be reached at i.bulbulahmed99@gmail.com

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“Refugees and Neighbors: Rohingya migration crisis and the Bangladesh experience”

Suma Haque

Most of the constitution of the neighboring countries of Bangladesh have incorporated human rights as fundamental rights. There is a well developed and upward body of jurisprudence on constitutional rights in such countries. Many neighboring countries have rectified or acceded to human rights treaties but the existing state of upbringing by these countries with such international human rights standards is not adequate. International Law of Refugees is a twig of International Human Rights Law. International refugee law mainly comprises of international apparatus that define basic standards for treatment of refugee. Now one of the most labored challenges confronting the world that is the problem of refugees, migrants, stateless persons and internally displaced persons.

The Rohingyas, a stateless tribal group loathe by many of Myanmar’s Buddhist majority, were strained to leave their homes since a Crimson crushing by the army in their home state of Rakhine. They are both stateless and refugees. The 1951 Refugee Convention defends refugees. It defines a refugee as an individual who is outside his or her country of nationality, has a well- founded anxiety of being persecuted because of religion, nationality, membership of a particular ethnic group and is not willing to avail him of the shelter of that country for fear of persecution. People who carry through this definition are eligible to the rights and bound by the duties contained in the 1951 Convention. The refusal of citizenship rights, denial of freedom of movement, expulsion campaigns, violence and physical agony imparted to the making of the Rohingya stateless and refugees.

Protecting refugees is the special obligation of States. Countries that have signed the 1951 Convention is obliged to protect refugees on their territory and treat them according to internationally recognized standards. Bangladesh cannot refuse to admit the Rohingya refugees seeking protection, though Bangladesh has not signed the 1951 convention. Because the principle of nonrefoulement forbid the return of a refugee to a territory where his life is vulnerable. This principle is binding to all States whether they have acceded to the 1951 Convention or 1967 Protocol.

To figure out the issue of Rohingya refugees these are not plain tasks. The case of Rohingya refugees in Bangladesh is one of the most tangled refugee situations in the world has been containing for more than three decades. It seems that Myanmar has acknowledged the persecution of its stateless Muslim minority and is considering giving citizenship to thousands of members of the group as a first step to finding a solution to the conflict with local  Rohingya Buddhists. A perdurable status for refugee is one of the ends the rhythm of displacement by resolving their pledge so that they can lead standard lives. The Traditionally, three stable solutions has been practiced to ending refugee crisis. The focuses on three aspects for the existing Rohingya-

  1. voluntary repatriation
  2. local integration
  3. resettlement.

The refugees are currently living in Bangladeshi camps but they may be moved to Thengar Char Island, which remains underwater for much of the year. It will be “terrible and crazy”. The government of Bangladesh may take an initiative to adopt a specific charter on human rights at the inter-governmental level to create a regional mechanism. This regional mechanism can address widespread human rights issues and concerns and provide remedies for cross border human rights violation. Establishment of such a mechanism can lead to greater harmonization and unification of human rights laws of the region, which can ultimately contribute much towards the goal of South Asian cooperation.

Suma Haque is a final year Law student of South East University, Dhaka, Bangladesh. She can be reached at Sumahaquesu@gmail.com

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Meal Skipping: Smartness or Diet Disaster?

Sabera

Are you very much conscious of being overweight? Do you think that skipping meal will help you to reduce some weight? Sometimes it’s a prestigious issue for some teenagers and youngsters who think that meal skipping is a part of smartness. In fact, there are several myths about meal skipping that are being believed by many people. For example, some people think that skipping meal can help to reduce  weight, some may even think that everything eaten late night turns to fat!

There are many people who skip breakfast or lunch by saying that they were too busy to have it. Even some people replace their lunch with snacks or fast food items. They may go for heavy dinner in the evening to minimize the effects of unhealthy eating throughout the day. Such type of meal skipping if continued for a long period of time can take a toll on body.

Researchers showed that meal skipping can help to reduce weight but there are certain conditions that are need to be fulfilled. Increasing only eating frequency (e.g. 6 times a day) will not help to reduce extra fat of the body as it can improve body’s metabolism rate. But this is not true all the time. Eating frequency can minimize cravings for food but it has little to do with metabolism. Quality and quantity of food should be the main consideration for a person who wants to reduce weight. Eating foods late night will not hamper the diet if proper calories are taken.

Meal skipping is also related to weight gain. Though it may sound surprising but the fact is people who remain hungry for a long time eventually develop cravings for food. And in this situation, the spicy, frozen, fried and oily foods seems to be more attracting. Thus craving leads to insensible and overeating resulting in weight gain. This type of larger meals after ‘no meals’ stretches the belly that makes it full. This stretched stomach pressurize the lower esophageal sphincter (LES). LES is the muscle ring of stomach that prevent back direction of acid that moves through the stomach. But too much pressure sends the stomach acid back up to the throat and cause heartburn.

Again, remain hungry for a long time can cause acidity, ulcers and gastroenteritis. Production of digestive enzymes is also hampered with meal skipping that causes poor food digestion resulting in gas, bloating, irritable bowel syndrome or diarrhea.  

When the body do not get food for a long period then chemical reaction of ketoacidosis starts that breakdown body chemicals and develop unpleasant smell. Not only this, empty stomach also reduces the amount of saliva production. Saliva normally flushes away unwanted bacteria but in absence of saliva dry mouth results that is also associated with bad breath.

Skipping meal can cause many disease conditions in long run. Generally it is obvious that when a person do not eat for a long time then the blood glucose level falls below normal. To compensate this some hormones are released that increases the blood pressure and cause headache. Again, when a heavy meal (including more carbohydrate and grains than normal level) is taken after remaining hungry for long period, it increases blood glucose level and delay insulin response. Is the situation continues it might cause diabetes in the long run.

Not only the physical health is hampered but also mental health is affected due to meal skipping. Researchers found that those who skip lunch turn to bad performers in professional life. They face lack of self-confidence, lack of focus, difficulty in concentrating, depression, irritation, frustration, decrease in patience, anxiety, slower pace of making decisions and emotionally drained feeling. Sometimes it has been observed that when the brain do not get adequate supply of glucose then it trigger muscular convulsions. Epilepsy and seizures are common in that case.

It is always desired to have a healthy body to live a healthy life. Proper diet and physical activity is very important to lead a balanced life. Skipping meal can prove to be a diet disaster. If meal is skipped (sometimes but not often), then diet should be planned with fresh fruits and vegetables and sufficient amount of water should be taken. Frequently meal skipping should be avoided as it has many short and long-term side effects on body.

Sabera Rahman is a master’s student of pharmaceutical science, she has completed her graduation under the department of Pharmacy, East West University. Sabera is a student correspondent at Association of Life Science and Engineering Writers (ALSEW). She can be reached at sabera.rahman@ymail.com

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Ovarian Cancer: Women Health is Precious!

sristy

To be a woman is not so easy. In different religious views, women are considered respectfully than others. We have born from a woman who is our mother. A woman has to play many roles in her family. But often we become careless about their health; sometimes we do not realize that the person who is always beside us may have some physical problem. Nowadays one of the most common problems among women is ovarian cancer.

In a straight, when cells in the body begin to grow abnormally cancer starts. Ovarian cancer has become a threat to women who have reached to menopause mainly. From the name, it can be understood that ovarian cancer occurs in ovaries. These organs are very fundamental for reproduction as they produce eggs and female hormones estrogen and progesterone.

Now if these ovaries play a vital role in women’s life then shouldn’t we care about the disease of ovaries? The answer must be yes from most of the person who can feel the pain of being a mother. But an awful fact is that our women most of the time do not know about that they might have ovarian cancer. A letter diagnosis of this serious issue can be even more harmful than earlier diagnosis.

Ovarian cancer has four main symptoms:

  • Persistent stomach pain
  • Difficulty eating or feeling full more quickly
  • Persistent bloating
  • Needing to urination more frequently

According to World Cancer Research Fund International, Ovarian cancer is the seventh most common cancer in women worldwide among 18 most common cancer, with 239,000 new cases diagnosed in 2012.

The countries with the highest incidence of ovarian cancer in 2012 are:

  • Fiji had the highest rate of ovarian cancer, followed by Latvia and Bulgaria.
  • The highest incidence of ovarian cancer was in Europe and Northern America; and the lowest incidence in Africa and Asia.
  • About 58% of ovarian cancer cases occurred in less developed countries.

Stage determination of ovarian cancer is done by International Federation of Gynecology and Obstetrics (FIGO) system. This system determines-

  • extent of the primary tumor (mainly denoted by the letter T)
  • absence or presence of metastasis to nearby lymph nodes (mainly denoted by the letter N)
  • absence or presence of distant metastasis (mainly denoted by the letter M)

After categorizing of T, N and M of a patient ovarian cancer is staged into four main categories-

Stage I:

The cancer is only within the ovary or ovaries. It has not extended to organs and tissues in the abdomen or pelvis, lymph nodes or to distant areas. Stage I has the sub-categories:

  • IA: Cancer has developed in one ovary and the tumor is confined to the inside of the ovary. There is no cancer on the external surface of the ovary.
  • IB: Cancer has developed in both of the ovaries but has not spread on their outer surfaces.
  • IC: Cancer has been developed one or both of the ovaries and tissues surrounding the tumor broke during surgery, whereas the outer surface of the diseased ovary is ruptured before surgery.

Stage II:

The cancer is developed in either one or both ovaries and spread in other organs but with the exception of lymph nodes or distant sites. There are two sub-categories of stage II:

  • IIA: Cancer that started in the ovaries has invaded the uterus or the fallopian tubes, or both.
  • IIB: Invasion of cancer into other nearby pelvic organs for instances the bladder, the sigmoid colon or the rectum.

Stage III:

The cancer is in one or both ovaries and following consequences occur:

  • Cancer has spread beyond the pelvis to the lining of the abdomen
  • Cancer has spread to lymph nodes in the back of the abdomen (retroperitoneal lymph nodes)

This stage has been divided into many of sub-divisions for the ease of treatment procedures. This stage is very serious for ovarian cancer patients. Appropriate treatment is critically required for the betterment of patient.

Stage IV:

This is the most progressed stage of ovarian cancer in which cancer has spread to the inside of the spleen, lungs, liver or other organs located outside the peritoneal cavity. Two sub-categories have been found for this stage:

  • IVA: Cancer cells are found in the fluid around the lungs. This is called a malignant pleural effusion.
  • IVB: Cancer has reached to the inside of the spleen or liver to lymph nodes also the retroperitoneal lymph nodes and to further organs or tissues outside the peritoneal cavity.

The main treatments for ovarian cancer are:

Surgery:

The main treatment for ovarian cancer is surgery which has mainly two goals:

  1.  Finding out how far the cancer has spread (staging)
  2. Removing as much of the cancer as possible (debulking)

For ovarian cancer, the most common operation includes the removal of ovaries, Uterus and both of the fallopian tubes. A layer of fatty tissue that covers the stomach area, called Omentum is removed as well.

Chemotherapy: To kill the cancer cells or minimize the size of tumors chemotherapy is employed which refers to the use of many chemotherapeutic agents or drugs through vein or mouth as well as abdomen. This treatment is mainly useful when the disease has spread ahead of the ovaries.

Targeted therapy: Targeted therapy has brought newer development in the treatment of ovarian cancer which has a selective effect on the cancer cell and causes reduced destruction of normal cells. Radiation therapy: While Radiation therapy is rarely used in developed countries due to its side effects. Radiation therapy includes high energy X-rays to destroy cancer cells or tumors.

As ovarian cancer patients are increasing day by day, alertness programs should be designed and executed for the betterment of treatment and minimizing the percentages of severing stage patients. Because it is about women health who brought us to the world!

Farzana Khan Sristy is a pharmacy student, has completed her graduation under the department of Pharmacy, East West University. She has interest on recent development of treatment methods and drugs. She is doing her research on Phytochemical activities. Farzana is a student correspondent at Association of Life Science and Engineering Writers (ALSEW). She can be reached at farzana_sristy@yahoo.com
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My experience regarding Sleep Paralysis: A Confusing Scientific Act of Sleep

Tahiya

All of us dream, right? I am not talking about day dreams and imaginations. I am indicating the dreams and nightmares that we go through while we are asleep. Usually, in my nightmares, either someone is chasing me, or trying to cut my throat, or harassing me, or creating such pressure on my body that I can’t even move my arms and legs. The last one, in particular, used to bother me the most. There was a phase when I used to really feel scared to go to sleep. When I discussed this with my closed ones, they suggested some technics of sleeping. I usually used to sleep on my back, but I was suggested to sleep side by side. I tried that but there was no positive result.

Some people told me that it is related to some demonic possession and invasion. I got more scared because I do watch a lot of horror movies. As, I was going through this experience on a regular basis, while sleeping and was not able to come out of it, I went to Google and searched “Why does my body feel numb during sleep and why do I feel intense pressure on my chest?”. Google was wise enough to direct me to the link of sleep paralysis. It was totally a new term to me. Then I researched on this topic and was able to figure out the scientific explanation behind this horrific experience.

The whole experience can be divided into three different factors- an intruder, Incubus, and unusual body experiences. Intruder normally refers to someone who makes an unwanted appearance in an individual’s life. This is the first feeling that is experienced in sleep paralysis. The second one comes with breathing problems and intense pressure over the chest area. Both intruder and incubus like feeling are considered to be a result of fear and insecurity in someone’s life. The final factor is the unusual body experiences which comprise of a blissful feeling of floating on air in some cases, and in other cases; the feeling comes as more of a scary situation.

Usually, when a person sleeps, s/he gets into the phase of rapid eye movement (REM) of sleep. It is a kind of sleep that occurs at intervals during the night and is characterized by rapid eye movements, more dreaming and bodily movement, and faster pulse and breathing.The brain remains active during the REM phase of sleep but the voluntary muscles of the body like arms, legs, fingers, anything that is under conscious control, are paralyzed.

This REM sleep contributes to the loss of muscle tone in the body so that we can’t move our bodies during dreams and nightmares and physically hurt ourselves. But it gets complicated when our brains get awakened in the middle of sleep but our bodies do not. This is termed as sleep paralysis, the mysterious term of suffering during sleep.

When I went through this on a regular basis, I used to experience the similar occurrences every time including- unable to move, the feeling of being held down, pressure on the chest, feeling someone’s presence in the room, breathing difficulties and obviously fear. Till now I did not consult any doctor but found out the possible causes for this problem. At that time, I was overusing caffeine, my sleeping time was irregular, my anxiety levels were immensely high and I used to sleep on my back.

Various neurotransmitters continuously pass important signals from the brain to the body. When the presence of certain neurotransmitter like acetylcholine increases in the brain during sleep, then this condition may occur. The research conducted by John Peever and Patricia Brooks, researchers of the University of Toronto focused on two different nerve receptors in the voluntary muscles- GABAB and GABAA/glycine. The latter receptor responds to both glycine and a different communication chemical called gamma-aminobutyric acid, or GABA, while the first response to GABA and not glycine.The researchers used drugs to “switch off” these receptors in rats and discovered that the only way to prevent sleep paralysis during REM was to shut both types off at the same time.

Consultation with the doctor is the most appropriate way to resolve this sleep disorder but self-measures can also be taken to get rid of this problem. Maintaining a specific sleeping schedule, breathing deeply, clenching feasts and wiggling of toes, trying to relax instead of fighting and most importantly, as the brain remains awake in that moment, try convincing you that it is just a sleep paralysis and it will be alright.

 

Tahiya Islam completed her graduation under Department of Pharmacy, East West University. She is an International student correspondent at Association of Life Science and Engineering Writers (ALSEW). Tahiya can be reached at tahiya945@gmail.com

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Addiction or Prescription

Niloy

Do you know about 48 million (older than 12) people are using prescription drugs for a nonmedical reason according to National Institute of Drug Abuse? It happens when a prescribed drug is being used for pleasure. Today it is becoming major and health concern in the USA and several European countries. Most common drugs that are used for being abused such as opioids, tranquilizers, sedatives, and stimulants. From BBC, it was found that the number of prescribed opioid rose from 76 million to 210 million, and also the number of prescribed sedative drugs increased from 4 million to 45 million during the same timeline. Addiction is considered as a brain illness and a form of dangerous physical dependence. You might have a question “why people are addicted toward prescription drugs?” Some proofs stated that nervousness, depression, genetic link, alcoholism, loneliness and peer pressure are considered as factors.

According to National Institute on Drug Abuse, these are three types of classes which indicate the prescription drugs that are being abused

  1. a) Opioids drugs(Morphine, Methadone,etc.) are used for pain treatment. It can also produce drowsiness, nausea, slow breathing. It may also create recreational by affecting the brain.
  2. B) CNS depressant drugs (Xanax, Valium,etc. ) (are often treated for anxiety, panic attack and also in sleep disorder . It also induce slow normal brain function to produce calming effect
  3. c) Stimulant drugs are (Concerta, Daytrana,etc.) used to treat attention, narcolepsy, depression and hyperacidity disorder. It stimulates the activity of norepinephrine and dopamine which increases the blood pressure and heart rate. They also have the ability to induce the euphoric effect.

People who are separated from family and friends and want to spend a lot of time alone are very prone to drug addicted.  They want to feel good or get high to rid of this loneliness. Besides opioids, CNS depressant and stimulant drugs have recreational effect and dependence.

They use prescribed medication in huge quantity. If a physician does not intend to prescribe a refill, then addicted patient tend to go from one to another to search for remedies. Withdrawal symptoms are associated with nervousness, nausea, sweating, vomiting, and dilated the pupil and skin goosebumps, etc. They seem to be extreme mood swing or appearing to be high or sedated. Losing their prescription is a common way so that more prescription will be written. Duration of sleeping might be increased or decreased due to abusing drugs.

Abusing medication can lead to several problems and even to the death. Prescription drugs can be harmful when are taken in higher doses or combined with drugs or consumed alcohol. Complication can be divided into two groups one is medical, and another one is physical.

In medical consequences opioids, drugs cause low blood pressure, slower breathing, and coma. Sedative and anti-anxiety drugs cause poor memory and slower breathing. Overdose may induce coma or death. Stimulant drugs cause dangerously high blood temperature, heart problems, seizures, hallucination, aggressiveness, etc.

These drugs stimulate the brain’s reward center result from by developing physical dependence and addiction. People who have tolerance need the higher dose for the activity.There are available treatments for counteracting by using non-addictive medications that can help interfere the symptoms of prescription drug addiction and regain control. The user may enter into a drug treatment facility and take the contribute to getting over with withdrawal symptoms may rise again into the new life. Counteracting the drug addiction is not a short process. It consists of two stages such as detoxification and rehabilitation. The first step in rehab to wean the patient slowly off the drugs. This process run till the dose is so low that complete withdrawal is no longer causes painful by using less addictive drugs at a decreasing amount of narcotics or derivatives under the same class.

When the first step is done, then the user is ready to undergo in second stages by entering into a prescription drug abuse rehabilitation facility. The service is run toward keeping the user about clear of medication while the user is going into intensive one on one and group therapy session with licensed physicians.

Regrettably, drugs have become the most prominent coping mechanism that people use to deal with life’s problems. It’s vital to remove anything from life which causes clear harms to both mental and physical health. Drug taking becomes a spiritual phenomenon of our society, which is indicating addiction rather than a way to heal or health recovering process. When you are looking for drug redhibition, then you are doing an important thing. But more fact is that you are taking over your life in lieu of letting the drugs to take control upon you. 

Niloy Ranjan Mondal is an undergrad student at department of Pharmacy in East West University, Dhaka Bangladesh. He can be reached at niloy12074@gmail.com

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Maraviroc

Tanjila

Acquired immunodeficiency syndrome (AIDS) was recognized as a disease in 1981 due to human immunodeficiency virus 1 (HIV-1). Soon, AIDS became a worldwide the biggest infectious disease globally due to its high progressive nature and lethality. For treatment, the first approach was nucleoside reverse transcriptase inhibitors, (NRTIs), then came the non-nucleoside reverse transcriptase inhibitors (NNRTIs), and in the mid-1990s, the first HIV-1 protease inhibitors. The highly active antiretroviral therapy (HAART) combination dosing regimens came that currently includes oral antiretroviral agents targeting host CD4 T-cells after HIV infection, the replication of HIV and the assembly stages. The recent development in HIV research is drugs targeting virus before the entry into the host cell, in attachment, fusion and penetration stages. Maraviroc is the drug preventing HIV1 from entry into the host cell, introducing a new class of drug therapy called chemokine co receptor antagonist or entry inhibitor.

During research work of HIV, scientists tried to find drugs targeting HIV entry to host cell.

The first licensed drug in this class, enfuvirtide, acted by binding to the viral envelope protein gp41 and preventing a post attachment of the viral entry. The drug had excellent efficacy in treatment experienced patients, but the mode of administration and cost of goods associated with a complex peptide drug had restricted its use.

Efforts had focused on small-molecule HIV-1 entry disrupters to enable oral delivery. It included the discovery of gp120-CD4-binding inhibitors and blockade of CXCR4 via antagonism but met challenges in efficacy and significant side effects, respectively.

The greatest success in targeting HIV-1 entry as a new mechanism has been developed as chemokine co receptor CCR5 antagonist.  

The chemokine receptors most commonly utilized by HIV-1 are CCR5 and/or CXCR4, with CCR5 being almost exclusively the essential and sole co receptor for infection of a person previously uninfected.

In 1996, CCR5 was identified as the predominant and essential coreceptor for HIV-1 cell entry, thereby triggering a widespread search for finding new therapeutic agents that targeted a host rather than a viral factor. The rationale for targeting viral entry as a novel approach to HIV therapy arose from the discovery of commonly occurring CCR5 mutation known as delta 32 mutation on chromosome 3.

Each CCR5 mutated gene results in the production of non-functional CCR5 co receptors (known as delta 32 homozygotes) that are not susceptible to HIV1 infection like typical CCR5 receptors. Delta 32 heterozygotes can be affected but the disease progression in delayed than normal CCR5 co receptors.

A decade later, CCR5 antagonist drug class included a number of investigational agents. The most advanced of these is Maraviroc, discovered in 2005 by Pfizer team and received approval by EMA in 2007 for treating CCR5 tropic HIV1 patients.

After 2 years, it was approved by FDA and current research is ongoing to develop Maraviroc related analogs with improved pharmacokinetics.

Amide substituent interacts with the predominantly lipophilic binding site on CCR5 and cyclobutyl amide analog was the most potent of the series.

Further studies established that S enantiomer of the cyclobutyl amide was the active isomer.

By keeping cyclobutyl substituent constant, piperadine analogs were studied, among them, tropane derivatives were highly potent inhibitors.

Cyclohexyl group and difluoro moiety give potent antiviral profile with lack affinity to hERG channel, resulting Maraviroc.

Maraviroc contains tertiary amine, two hydrophobic groups, one heteroaryl group, these are main elements of CCR5 antagonists.

The chemokine co receptors of the host cell are of g-protein coupled receptor (GPCR) super family. They are mainly of 2 variants, for interacting with HIV 1 variant – CCR5 and CXCR4. Some HIV variant selectively binds to CCR5 (CCR5 tropic variant), some use CXCR4 (CXCR4 tropic variant) and some use both (dual-tropic strain) to infect the host.

To inhibit the interaction of HIV with the host cell, CCR5 antagonist needs to bind specifically to the CCR5 molecule of the host. So bound CCR5 is blocked from binding the viral gp120 that prevents the conformational change of gp41, which prevents viral particle entry to the host cell. Without penetration, HIV can’t replicate and infect the host.  

Unlike reverse transcriptase inhibitor and protease inhibitors, co receptor antagonists act outside the infected cell. They are unique because they target host cells like T cell or macrophages rather than viral component having clinical advantages. Maraviroc is the only HIV-1 CCR5-based entry inhibitor to date approved by FDA and research and development of other CCR5 inhibitors are going on.

Tanjila Islam is a graduated pharmacist from East West University, Dhaka, Bangladesh. She can be reached at tanjila1524@gmail.com

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‘Importance of Memorialization in response to the aftermath of Bangladesh Liberation War 1971’

Mustak Ahmed Shimul

Memorialization, in general, refers to the method of conserving memories of people and incident. Memorialization is an ideal opportunity for us to show our appreciation for those who were prepared to sacrifice their lives for their country. Memorialization is used to honor the victims of human rights abuses and it ensures transitional justice. The importance of memorialization in post conflict society is necessary. Within this global context, remembering is a way to continue the struggle against forces of bigotry, dogmatism, hatred, and violence. Memorialization is an ongoing process, one of learning that can open up many narratives and should have room for many personal perspectives.

The history of memorialization in Bangladesh begins from the Language Movement in 1952 and finally get motion in the climactic event of Liberation War in 1971, through which Bangladesh was liberated.Rayerbazaar Boddhobhumi was fabricated to memorialize the death of many of the countries shrewd intellectuals, who were killed by the Pakistani military services. The Memorial was planned by designer Farid Uddin Ahmed and architect Zami Al Shafi. National Martyrs’ Memorial located at Savar, symbolizes the heroism of the martyrs who dedicated their lives for the liberation of Bangladesh.

Memorialization also includes Roads, e.g. Bir Uttam Shaheed Khaza Nizam Uddin Bhuiyan. Trophy, e.g. Birshreshto Matiur Rahman trophy named after Birshreshto Matiur Rahman is awarded for the top-grade Individual Research Paper of Air Wing in Defense Services Command and Staff College. Museum, e.g. Liberation War Museum. Books e.g. Shahzaman Mozumder’s The Guerrilla: A Personal Memorandum of 1971. We have a couple of books written by participating fighter. These books are also the part of memorialization.

Memorialization process is going on in different countries. The Tuol Sleng Genocide Museum is a museum in the capital of Cambodia, put down the Cambodian genocide. In Rwanda, there are eight killing memorials which containing the memories of Genocide war of 1994.

Only memorialization is not the means to conserving the memories rather its uses in practical life can play an indispensable role. Publicity of memorialization by the institution is extremely essential. A basal component for successful memorialization is the collaboration between the authorities, citizens and civil society, especially representatives of those directly affected by past events. Memorialization processes should be centered on the victims and designed to empower them.

Mustak Ahmed Shimul is a student of  Department of Law, South-East University. He can be reached at shimulahmed52@gmail.com.

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