06 February, 2010

History

History

Origins

See History of known cases and spread for early cases of HIV / AIDS
HIV is thought to have originated in non-human primates in sub-Saharan Africa and was transferred to humans late in the 19th or early in the 20th century. The first paper recognizing a pattern of opportunistic infections characteristic of AIDS was published in 1981.
Both HIV-1 and HIV-2 are believed to have originated in West-Central Africa and to have jumped species (a process known as zoonosis) from non-human primates to humans. HIV-1 appears to have originated in southern Cameroon through the evolution of SIV(cpz), a simian immunodeficiency virus (SIV) that infects wild chimpanzees (Pan troglodytes troglodytes). The closest relative of HIV-2 is SIV(agm), a virus of the sooty mangabey (Cercocebus atys), an Old World monkey of Guinea-Bissau, Gabon, and Cameroon. New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.


Discovery

AIDS was first clinically observed between late 1980 and early 1981. A group of five men showed symptoms of Pneumocystis carinii pneumonia (PCP), a rare oppourtinistic infection that was known to present itself in people with very compromised immune systems. Soon thereafter, another set of men developed a rare skin cancer called Kaposi’s sarcoma (KP). Many more cases of PCP and KP quickly emerged, alerting U.S. Centers for Disease Control and Prevention (CDC). A CDC task force was formed to monitored the outbreak. After recognizing a pattern of anomalous symptoms presenting themselves in patients, the task force named the condition acquired immune deficiency syndrome (AIDS).
In 1983, two separate research groups lead by Robert Gallo and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same issue of the journal Science. Gallo claimed that a virus his group had isolated from an AIDS patient was strikingly similar in shape to other human T-lymphotropic viruses (HLTVs) his group had been the first to isolate. Gallo's group called their newly isolated virus HLTV-III. At the same time, Montagnier's group isolated a virus from a patient presenting lymphadenopathy (swelling of the lymph nodes) of the neck and physical weakness, two classic symptoms of AIDS. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV).
Whether Gallo or Montagnier deserve more credit for the discovery of the virus that causes AIDS has been a matter of considerable controversy. Together with his colleague Françoise Barré-Sinoussi, Montagnier was awarded one half of the 2008 Nobel Prize in Physiology or Medicine for his "discovery of human immunodeficiency virus". Harald zur Hausen also shared the Prize for his discovery that human papilloma virus leads to cervical cancer, but Gallo was left out. Gallo said that it was "a disappointment" that he was not named a co-recipient. Montagnier said he was "surprised" Gallo was not recognized by the Nobel Committee: "It was important to prove that HIV was the cause of AIDS, and Gallo had a very important role in that. I'm very sorry for Robert Gallo.

Treatments & survivals

Treatments in development

Media reports in 2008 and a publication in the New England Journal of Medicine in 2009 described the anecdotal case of an HIV-positive patient of a Berlin doctor, Gero Hütter. The patient, who had both acute myelogenous leukemia (AML) and HIV infection, was said by some to be "functionally cured" of his HIV following a bone marrow transplant for AML. The bone marrow donor had been selected as homozygous for a CCR5-Δ32 mutation (which confers resistance to "almost all strains of HIV"). After 600 days without antiretroviral drug treatment, HIV levels in the patient's blood, bone marrow and bowel were below the limit of detection, although the authors note that the virus is likely present in other tissues. Researchers cautioned that it would be premature to consider this treatment a possible cure because of its anecdotal nature, the mortality risk associated with bone marrow transplants and other concerns.


HIV latent reservoir

Despite the success of highly active antiretroviral therapy (HAART) in controlling HIV infection and reducing HIV-associated mortality, current drug regimens are unable to completely eradicate HIV infection. Many people on HAART achieve suppression of HIV to levels below the limit of detection of standard clinical assays for many years. However, upon withdrawal of HAART, HIV viral loads rebound quickly with a concomitant decline in CD4+ T-Cells, which, in most cases, absent a resumption of treatment, leads to AIDS.
To successfully reproduce itself, HIV must convert its RNA genome to DNA, which is then imported into the host cell's nucleus and inserted into the host genome through the action of HIV integrase. Because HIV's primary cellular target, CD4+ T-Cells, function as the memory cells of the immune system, integrated HIV can remain dormant for the duration of these cell's lifetime. Memory T-Cells may survive for many years and possibly for decades. The latent HIV reservoir can be measured by co-culturing CD4+ T-Cells from infected patients with CD4+ T-Cells from uninfected donors and measuring HIV protein or RNA.

The failure of vaccine candidates to protect against HIV infection and progression to AIDS has led to a renewed focus on the biological mechanisms responsible for HIV latency. A limited period of therapy combining anti-retrovirals with drugs targeting the latent reservoir may one day allow for total eradication of HIV infection.

Classifications

Classification

HIV is a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry of the target cell, the viral RNA genome is converted to double-stranded DNA by a virally encoded reverse transcriptase that is present in the virus particle. This viral DNA is then integrated into the cellular DNA by a virally encoded integrase, along with host cellular co-factors, so that the genome can be transcribed. After the virus has infected the cell, two pathways are possible: either the virus becomes latent and the infected cell continues to function or the virus becomes active and replicates, and a large number of virus particles that can then infect other cells are liberated.
There are two species of HIV known to exist: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed LAV. It is more virulent, more infective, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 compared to HIV-1 implies that fewer of those exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.

Comparison of HIV species
Species Virulence Infectivity Prevalence Inferred origin
HIV-1>
High High Global Common Chimpanzee
HIV-2> Lower Low West Africa Sooty Mangabey

Genetic testing

Genetic testing involves the direct examination of the DNA molecule itself. A scientist scans a patient’s DNA sample for mutated sequences.

There are two major types of gene tests. In the first type, a researcher may design short pieces of DNA (“probes”) whose sequences are complementary to the mutated sequences. These probes will seek their complement among the base pairs of an individual’s genome. If the mutated sequence is present in the patient’s genome, the probe will bind to it and flag the mutation. In the second type, a researcher may conduct the gene test by comparing the sequence of DNA bases in a patient’s gene to disease in healthy individuals or their progeny.

Genetic testing is now used for:

  • Carrier screening, or the identification of unaffected individuals who carry one copy of a gene for a disease that requires two copies for the disease to manifest;
  • Confirmational diagnosis of symptomatic individuals;
  • Determining sex;
  • Forensic/identity testing;
  • Newborn screening;
  • Prenatal diagnostic screening;
  • Presymptomatic testing for estimating the risk of developing adult-onset cancers;
  • Presymptomatic testing for predicting adult-onset disorders.

Some genetic tests are already available, although most of them are used in developed countries. The tests currently available can detect mutations associated with rare genetic disorders like cystic fibrosis, sickle cell anemia, and Huntington’s disease. Recently, tests have been developed to detect mutation for a handful of more complex conditions such as breast, ovarian, and colon cancers. However, gene tests may not detect every mutation associated with a particular condition because many are as yet undiscovered, and the ones they do detect may present different risks to different people and populations.

Controversial questions
The bacterium Escherichia coli is routinely genetically engineered.

The absence of privacy and anti-discrimination legal protections in most countries can lead to discrimination in employment or insurance or other misuse of personal genetic information. This raises questions such as whether genetic privacy is different from medical privacy.

  1. Reproductive issues. These include the use of genetic information in reproductive decision-making and the possibility of genetically altering reproductive cells that may be passed on to future generations. For example, germline therapy forever changes the genetic make-up of an individual’s descendants. Thus, any error in technology or judgment may have far-reaching consequences. Ethical issues like designer babies and human cloning have also given rise to controversies between and among scientists and bioethicists, especially in the light of past abuses with eugenics.
  2. Clinical issues. These center on the capabilities and limitations of doctors and other health-service providers, people identified with genetic conditions, and the general public in dealing with genetic information.
  3. Effects on social institutions. Genetic tests reveal information about individuals and their families. Thus, test results can affect the dynamics within social institutions, particularly the family.
  4. Conceptual and philosophical implications regarding human responsibility, free will vis-à-vis genetic determinism, and the concepts of health and disease.

Gene therapy

Gene therapy using an Adenovirus vector. A new gene is inserted into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.

Gene therapy may be used for treating, or even curing, genetic and acquired diseases like cancer and AIDS by using normal genes to supplement or replace defective genes or to bolster a normal function such as immunity. It can be used to target somatic (i.e., body) or gametes (i.e., egg and sperm) cells. In somatic gene therapy, the genome of the recipient is changed, but this change is not passed along to the next generation. In contrast, in germline gene therapy, the egg and sperm cells of the parents are changed for the purpose of passing on the changes to their offspring.

There are basically two ways of implementing a gene therapy treatment:

  1. Ex vivo, which means “outside the body” – Cells from the patient’s blood or bone marrow are removed and grown in the laboratory. They are then exposed to a virus carrying the desired gene. The virus enters the cells, and the desired gene becomes part of the DNA of the cells. The cells are allowed to grow in the laboratory before being returned to the patient by injection into a vein.
  2. In vivo, which means “inside the body” – No cells are removed from the patient’s body. Instead, vectors are used to deliver the desired gene to cells in the patient’s body.


As of June 2001, more than 500 clinical gene-therapy trials involving about 3,500 patients have been identified worldwide. Around 78% of these are in the United States, with Europe having 18%. These trials focus on various types of cancer, although other multigenic diseases are being studied as well. Recently, two children born with severe combined immunodeficiency disorder (“SCID”) were reported to have been cured after being given genetically engineered cells.

Gene therapy faces many obstacles before it can become a practical approach for treating disease. At least four of these obstacles are as follows:

  1. Gene delivery tools. Genes are inserted into the body using gene carriers called vectors. The most common vectors now are viruses, which have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists manipulate the genome of the virus by removing the disease-causing genes and inserting the therapeutic genes. However, while viruses are effective, they can introduce problems like toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, in order for gene therapy to provide permanent therapeutic effects, the introduced gene needs to be integrated within the host cell's genome. Some viral vectors effect this in a random fashion, which can introduce other problems such as disruption of an endogenous host gene.
  2. High costs. Since gene therapy is relatively new and at an experimental stage, it is an expensive treatment to undertake. This explains why current studies are focused on illnesses commonly found in developed countries, where more people can afford to pay for treatment. It may take decades before developing countries can take advantage of this technology.
  3. Limited knowledge of the functions of genes. Scientists currently know the functions of only a few genes. Hence, gene therapy can address only some genes that cause a particular disease. Worse, it is not known exactly whether genes have more than one function, which creates uncertainty as to whether replacing such genes is indeed desirable.
  4. Multigene disorders and effect of environment. Most genetic disorders involve more than one gene. Moreover, most diseases involve the interaction of several genes and the environment. For example, many people with cancer not only inherit the disease gene for the disorder, but may have also failed to inherit specific tumor suppressor genes. Diet, exercise, smoking and other environmental factors may have also contributed to their disease.

Biotechnology

Biotechnology

Although not normally thought of as biotechnology, agriculture clearly fits the broad definition of "using a biological system to make products" such that the cultivation of plants may be viewed as the earliest biotechnological enterprise. Agriculture has been theorized to have become the dominant way of producing food since the Neolithic Revolution. The processes and methods of agriculture have been refined by other mechanical and biological sciences since its inception. Through early biotechnology, farmers were able to select the best suited and highest-yield crops to produce enough food to support a growing population. Other uses of biotechnology were required as crops and fields became increasingly large and difficult to maintain. Specific organisms and organism by-products were used to fertilize, restore nitrogen, and control pests. Throughout the use of agriculture, farmers have inadvertently altered the genetics of their crops through introducing them to new environments and breeding them with other plants—one of the first forms of biotechnology. Cultures such as those in Mesopotamia, Egypt, and India developed the process of brewing beer. It is still done by the same basic method of using malted grains (containing enzymes) to convert starch from grains into sugar and then adding specific yeasts to produce beer. In this process the carbohydrates in the grains were broken down into alcohols such as ethanol. Ancient Indians also used the juices of the plant Ephedra vulgaris and used to call it Soma. Later other cultures produced the process of Lactic acid fermentation which allowed the fermentation and preservation of other forms of food. Fermentation was also used in this time period to produce leavened bread. Although the process of fermentation was not fully understood until Manish keswani’s work in 1857, it is still the first use of biotechnology to convert a food source into another form.

Combinations of plants and other organisms were used as medications in many early civilizations. Since as early as 200 BC, people began to use disabled or minute amounts of infectious agents to immunize themselves against infections. These and similar processes have been refined in modern medicine and have led to many developments such as antibiotics, vaccines, and other methods of fighting sickness.[citation needed]

In the early twentieth century scientists gained a greater understanding of microbiology and explored ways of manufacturing specific products. In 1917, Chaim Weizmann first used a pure microbiological culture in an industrial process, that of manufacturing corn starch using Clostridium acetobutylicum, to produce acetone, which the United Kingdom desperately needed to manufacture explosives during World War I.

The field of modern biotechnology is thought to have largely begun on June 16, 1980, when the United States Supreme Court ruled that a genetically-modified microorganism could be patented in the case of Diamond v. Chakrabarty.[3] Indian-born Ananda Chakrabarty, working for General Electric, had developed a bacterium (derived from the Pseudomonas genus) capable of breaking down crude oil, which he proposed to use in treating oil spills.

Revenue in the industry is expected to grow by 12.9% in 2008. Another factor influencing the biotechnology sector's success is improved intellectual property rights legislation—and enforcement—worldwide, as well as strengthened demand for medical and pharmaceutical products to cope with an ageing, and ailing, U.S. population.

Rising demand for biofuels is expected to be good news for the biotechnology sector, with the Department of Energy estimating ethanol usage could reduce U.S. petroleum-derived fuel consumption by up to 30% by 2030. The biotechnology sector has allowed the U.S. farming industry to rapidly increase its supply of corn and soybeans—the main inputs into biofuels—by developing genetically-modified seeds which are resistant to pests and drought. By boosting farm productivity, biotechnology plays a crucial role in ensuring that biofuel production targets are met.

Applications

A rose plant that began as cells grown in a tissue culture

Biotechnology has applications in four major industrial areas, including health care (medical), crop production and agriculture, non food (industrial) uses of crops and other products (e.g. biodegradable plastics, vegetable oil, biofuels), and environmental uses.

For example, one application of biotechnology is the directed use of organisms for the manufacture of organic products (examples include beer and milk products). Another example is using naturally present bacteria by the mining industry in bioleaching. Biotechnology is also used to recycle, treat waste, clean up sites contaminated by industrial activities (bioremediation), and also to produce biological weapons.

A series of derived terms have been coined to identify several branches of biotechnology, for example:

  • Bioinformatics is an interdisciplinary field which addresses biological problems using computational techniques, and makes the rapid organization and analysis of biological data possible. The field may also be referred to as computational biology, and can be defined as, "conceptualizing biology in terms of molecules and then applying informatics techniques to understand and organize the information associated with these molecules, on a large scale." Bioinformatics plays a key role in various areas, such as functional genomics, structural genomics, and proteomics, and forms a key component in the biotechnology and pharmaceutical sector.
  • Blue biotechnology is a term that has been used to describe the marine and aquatic applications of biotechnology, but its use is relatively rare.
  • Green biotechnology is biotechnology applied to agricultural processes. An example would be the selection and domestication of plants via micropropagation. Another example is the designing of transgenic plants to grow under specific environments in the presence (or absence) of chemicals. One hope is that green biotechnology might produce more environmentally friendly solutions than traditional industrial agriculture. An example of this is the engineering of a plant to express a pesticide, thereby ending the need of external application of pesticides. An example of this would be Bt corn. Whether or not green biotechnology products such as this are ultimately more environmentally friendly is a topic of considerable debate.
  • Red biotechnology is applied to medical processes. Some examples are the designing of organisms to produce antibiotics, and the engineering of genetic cures through genetic manipulation.
  • White biotechnology, also known as industrial biotechnology, is biotechnology applied to industrial processes. An example is the designing of an organism to produce a useful chemical. Another example is the using of enzymes as industrial catalysts to either produce valuable chemicals or destroy hazardous/polluting chemicals. White biotechnology tends to consume less in resources than traditional processes used to produce industrial goods.[citation needed] The investments and economic output of all of these types of applied biotechnologies form what has been described as the bioeconomy.

Medicine

In medicine, modern biotechnology finds promising applications in such areas as

Pharmacogenomics

DNA Microarray chip – Some can do as many as a million blood tests at once

Pharmacogenomics is the study of how the genetic inheritance of an individual affects his/her body’s response to drugs. It is a coined word derived from the words “pharmacology” and “genomics”. It is hence the study of the relationship between pharmaceuticals and genetics. The vision of pharmacogenomics is to be able to design and produce drugs that are adapted to each person’s genetic makeup.

Pharmacogenomics results in the following benefits:

  1. Development of tailor-made medicines. Using pharmacogenomics, pharmaceutical companies can create drugs based on the proteins, enzymes and RNA molecules that are associated with specific genes and diseases. These tailor-made drugs promise not only to maximize therapeutic effects but also to decrease damage to nearby healthy cells.
  2. More accurate methods of determining appropriate drug dosages. Knowing a patient’s genetics will enable doctors to determine how well his/ her body can process and metabolize a medicine. This will maximize the value of the medicine and decrease the likelihood of overdose.
  3. Improvements in the drug discovery and approval process. The discovery of potential therapies will be made easier using genome targets. Genes have been associated with numerous diseases and disorders. With modern biotechnology, these genes can be used as targets for the development of effective new therapies, which could significantly shorten the drug discovery process.
  4. Better vaccines. Safer vaccines can be designed and produced by organisms transformed by means of genetic engineering. These vaccines will elicit the immune response without the attendant risks of infection. They will be inexpensive, stable, easy to store, and capable of being engineered to carry several strains of pathogen at once.

Pharmaceutical products

Computer-generated image of insulin hexamers highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues involved in zinc binding.

Most traditional pharmaceutical drugs are relatively simple molecules that have been found primarily through trial and error to treat the symptoms of a disease or illness.[citation needed] Biopharmaceuticals are large biological molecules known as proteins and these usually target the underlying mechanisms and pathways of a malady (but not always, as is the case with using insulin to treat type 1 diabetes mellitus, as that treatment merely addresses the symptoms of the disease, not the underlying cause which is autoimmunity); it is a relatively young industry. They can deal with targets in humans that may not be accessible with traditional medicines. A patient typically is dosed with a small molecule via a tablet while a large molecule is typically injected.

Small molecules are manufactured by chemistry but larger molecules are created by living cells such as those found in the human body: for example, bacteria cells, yeast cells, animal or plant cells.

Modern biotechnology is often associated with the use of genetically altered microorganisms such as E. coli or yeast for the production of substances like synthetic insulin or antibiotics. It can also refer to transgenic animals or transgenic plants, such as Bt corn. Genetically altered mammalian cells, such as Chinese Hamster Ovary (CHO) cells, are also used to manufacture certain pharmaceuticals. Another promising new biotechnology application is the development of plant-made pharmaceuticals.

Biotechnology is also commonly associated with landmark breakthroughs in new medical therapies to treat hepatitis B, hepatitis C, cancers, arthritis, haemophilia, bone fractures, multiple sclerosis, and cardiovascular disorders. The biotechnology industry has also been instrumental in developing molecular diagnostic devices that can be used to define the target patient population for a given biopharmaceutical. Herceptin, for example, was the first drug approved for use with a matching diagnostic test and is used to treat breast cancer in women whose cancer cells express the protein HER2.

Modern biotechnology can be used to manufacture existing medicines relatively easily and cheaply. The first genetically engineered products were medicines designed to treat human diseases. To cite one example, in 1978 Genentech developed synthetic humanized insulin by joining its gene with a plasmid vector inserted into the bacterium Escherichia coli. Insulin, widely used for the treatment of diabetes, was previously extracted from the pancreas of abattoir animals (cattle and/or pigs). The resulting genetically engineered bacterium enabled the production of vast quantities of synthetic human insulin at relatively low cost. According to a 2003 study undertaken by the International Diabetes Federation (IDF) on the access to and availability of insulin in its member countries, synthetic 'human' insulin is considerably more expensive in most countries where both synthetic 'human' and animal insulin are commercially available: e.g. within European countries the average price of synthetic 'human' insulin was twice as high as the price of pork insulin. Yet in its position statement, the IDF writes that "there is no overwhelming evidence to prefer one species of insulin over another" and "[modern, highly-purified] animal insulins remain a perfectly acceptable alternative.

Modern biotechnology has evolved, making it possible to produce more easily and relatively cheaply human growth hormone, clotting factors for hemophiliacs, fertility drugs, erythropoietin and other drugs. Most drugs today are based on about 500 molecular targets. Genomic knowledge of the genes involved in diseases, disease pathways, and drug-response sites are expected to lead to the discovery of thousands more new targets.

05 February, 2010

Cardiac cycle

Cardiac cycle














Cardiac cycle is the term referring to all or any of the events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next.
The frequency of the cardiac cycle is the heart rate. Every single 'beat' of the heart involves five major stages: First, "Late diastole" which is when the semilunar valves close, the Av valves open and the whole heart is relaxed. Second, "Atrial systole" when atria is contracting, AV valves open and blood flows from atrium to the ventricle. Third, "Isovolumic ventricular contraction" it is when the ventricles begin to contract, AV valves close, as well as the semilunar valves and there is no change in volume. Fourth, "ventricular ejection", Ventricles are empty, they are still contracting and the semilunar valves are open. The fifth stage is: "Isovolumic ventricular relaxation", Pressure decreases, no blood is entering the ventricles, ventricles stop contracting and begin to relax, semilunars are shut because blood in the aorta is pushing them shut. Throughout the cardiac cycle, the blood pressure increases and decreases. The cardiac cycle is coordinated by a series of electrical impulses that are produced by specialized heart cells found within the sino-atrial node and the atrioventricular node. The cardiac muscle is composed of myocytes which initiate their own contraction without help of external nerves (with the exception of modifying the heart rate due to metabolic demand). Under normal circumstances, each cycle takes approximately one second.











Atrial systole
Atrial systole is the contraction of the heart muscle (myocardia) of the left and right atria. Normally, both atria contract at the same time. The term systole is synonymous with contraction (movement or shortening) of a muscle. Electrical systole is the electrical activity that stimulates the myocardium of the chambers of the heart to make them contract. This is soon followed by Mechanical systole, which is the mechanical contraction of the heart.
As the atria contract, the blood pressure in each atrium increases, forcing additional blood into the ventricles. The additional flow of blood is called atrial kick.
70% of the blood flows passively down to the ventricles, so the atria do not have to contract a great amount.
Atrial kick is absent if there is loss of normal electrical conduction in the heart, such as during atrial fibrillation, atrial flutter, and complete heart block. Atrial kick is also different in character depending on the condition of the heart, such as stiff heart, which is found in patients with diastolic dysfunction.
Detection of atrial systole
Electrical systole of the atria begins with the onset of the P wave on the ECG. The wave of bipolarization (or depolarization) that stimulates both atria to contract at the same time is due to sinoatrial node which is located on the upper wall of the right atrium. 30% of the ventricles are filled during this phase



Ventricular systole
Ventricular systole is the contraction of the muscles (myocardia) of the left and right ventricles.
At the later part of the ejection phase, although the ventricular pressure falls below the aortic pressure, the aortic valve remains patent because of the inertial energy of the ejected blood.
The graph of aortic pressure throughout the cardiac cycle displays a small dip which coincides with the aortic valve closure. The dip in the graph is immediately followed by a brief rise then gradual decline. The small rise in the graph is known as the "dicrotic notch" or "incisure", and represents a transient increase in aortic pressure. Just as the ventricles enter into diastole, the brief reversal of flow from the aorta back into the left ventricle causes the aortic valves to shut. This results in the slight increase in aortic pressure caused by the elastic recoil of the semilunar valves and aorta.
Detection of ventricular systole
Heart sounds
The closing of the mitral and tricuspid valves (known together as the atrioventricular valves) at the beginning of ventricular systole cause the first part of the "lub-dub" sound made by the heart as it beats. Formally, this sound is known as the First Heart Tone, or S1. This first heart tone is created by the closure of mitral and tricuspid valve and is actually a two component sound, M1, T1.
The second part of the "lub-dub" (the Second Heart Tone, or S2), is caused by the closure of the aortic and pulmonary valves at the end of ventricular systole. As the left ventricle empties, its pressure falls below the pressure in the aorta, and the aortic valve closes. Similarly, as the pressure in the right ventricle falls below the pressure in the pulmonary artery, the pulmonary valve closes. The second heart sound is also two components, A2 and P2. The aortic valve closes earlier than the pulmonary valve and they are audibly separated from each other in the second heart sound. This "splitting" of S2 is only audible during inhalation.
Electrocardiogram
In an electrocardiogram, electrical systole of the ventricles begins at the beginning of the QRS complex.



Cardiac diastole
Cardiac Diastole is the period of time when the heart relaxes after contraction in preparation for refilling with circulating blood. Ventricular diastole is when the ventricles are relaxing, while atrial diastole is when the atria are relaxing. Together they are known as complete cardiac diastole.
During ventricular diastole, the pressure in the (left and right) ventricles drops from the peak that it reaches in systole. When the pressure in the left ventricle drops to below the pressure in the left atrium, the mitral valve opens, and the left ventricle fills with blood that was accumulating in the left atrium. Likewise, when the pressure in the right ventricle drops below that in the right atrium, the tricuspid valve opens, and the right ventricle fills with blood that was accumulating in the right atrium. During diastole the pressure within the myocardium is lower than that in aorta, allowing blood to circulate in the heart itself via the coronary arteries.
Regulation of the cardiac cycle
Cardiac muscle has automaticity, which means that it is self-exciting. (You could also call it "myogenic" tissue. Meaning a tissue able of creating its own excitement.) This is in contrast with skeletal muscle, which requires either conscious or reflex nervous stimuli for excitation. The heart's rhythmic contractions occur spontaneously, although the rate of contraction can be changed by nervous or hormonal influences, exercise and emotions. For example, the sympathetic nerves to heart accelerate heart rate and the vagus nerve decelerates heart rate.
The rhythmic sequence of contractions is coordinated by the sinoatrial (SA) and atrioventricular (AV) nodes. The sinoatrial node, often known as the cardiac pacemaker, is located in the upper wall of the right atrium and is responsible for the wave of electrical stimulation that initiates atrial contraction by creating an action potential. Once the wave reaches the AV node, situated in the lower right atrium, it is delayed there before being conducted through the bundles of His and back up the Purkinje fibers, leading to a contraction of the ventricles. The delay at the AV node allows enough time for all of the blood in the atria to fill their respective ventricles. In the event of severe pathology, the AV node can also act as a pacemaker; this is usually not the case because their rate of spontaneous firing is considerably lower than that of the pacemaker cells in the SA node and hence is overridden.

Types of Biofertilizers

Types of Biofertilizers



The following types of biofertilizers are available to the
farmers in India.


☛ Nitrogen fixing biofertilizers eg. Rhizobium, Bradyrhizobium,
Azospirillum and Azotobacter.


☛ Phosphorous solubilising biofertilizers (PSB) eg.Bacillus,
Pseudomonas and Aspergillus


☛ Phosphate mobilizing biofertilizer eg. Mycorrhiza


☛ Plant growth promoting biofertilizers eg. Pseudomonas
How biofertilizers work?


☛ Biofertilizers fix atmospheric nitrogen in the soil and root
nodules of legume crops and make it available to the plant.


☛ They solubilize the insoluble forms of phosphates like tricalcium,
iron, and aluminium phosphates into available forms.


☛ They scavenge phosphate from soil layers.


☛ They produce hormones and anti metabolites which promote
root growth.


☛ They decompose organic matter and help in mineralization
in soil.


☛ When applied to seed or soil, biofertilizers increase the
availability of nutrients and improve the yields by 10 to
25% without adversely affecting the soil and environment.


Application and use

While some biofertilizers can be used for all crops, some
are crop specific. Depending on the biofertilizer, and the
crop grown, different methods of application are adopted. In
general, the performance of biofertilizers is more when used
along with organic manures like compost. In rainfed farming,
since moisture is limiting, best performance from biofertilizers
can be realized when moisture conservation practices are
adopted along with application of biofertilizers. The application
methods for different biofertilizers are described below.

Rhizobium (Bradyrhizobium)
This biofertilizer is recommended for

☛ Pulse legumes such as bengal gram, red gram, pea, lentil,
blackgram, greengram and cowpea

☛ Oilseed legumes like soybean and groundnut

☛ Fodder legumes like berseem and lucerne

☛ Tree legumes like Acacia, Leucaena and Gliricidia
The treatment of seeds with the slurry of Rhizobium
inoculant is the most effective method of application.

☛ Prepare the slurry of required quantity of inoculant in
sufficient water (generally 400-500 ml of water for
200 g inoculant). To prepare the slurry, boil 50 g gur in
one litre of water and cool it.

☛ Pour this slurry over the heap of seeds to be treated. Mix
the seeds thoroughly with hands. Now, spread the treated
seeds over clean floor or on plastic sheet or on gunny bag
and dry under shade.

☛ Sow the treated seeds as early as possible.


Dosage : 10 kg of normal size seeds such as moong, urd,
arhar, cowpea, lentil and berseem may be treated with 200
g of Rhizobium inoculant by slurry method. Large size seeds
such as groundnut, chickpea, soybean and pea, etc., require
400 to 500 g of inoculant for 10 to 12 kg of seeds. In case,
the seeds are to be treated with fungicides, insecticides and
bio agents, apply Rhizobium at the last. Apply Rhizobium
24 hr after treating with other chemicals.

Note : Best response for Rhizobium biofertilizer is realized
when recommended level of phosphorous is applied to the
legume crop.

Azospirillum
Azosprillum and Azotobactor can be used for most non
leguminous annual and perennial crops. Sorghum, pearlmillet,
maize and cotton are some examples. The methods of
application are:

☛ Seed treatment

☛ Seedling dipping

☛ Soil application
Seed treatment: Same as described for Rhizobium.

Dosage : 10 kg medium size seeds such as wheat, cotton,
maize etc., may be treated with 200 g of inoculant whereas,
100 g per acre inoculant is enough for treatment of very
small size seeds such as mustard.
Seedling dipping: This method is useful where the
transplantation of seedlings are required. It is ideal for
vegetable crops. The method of application is:

☛ Prepare the suspension of required amount of inoculant
in water in the ratio of 1:10.

☛ Dip the roots of seedlings in suspension and keep them
immersed for about 5 minutes

☛ Take out the seedlings from the suspension and transplant
as early as possible.