Lungs cancer

•  Lung cancer is the number-one cause of cancer deaths in both men and women in the U.S. and worldwide.
• Cigarette smoking is the principal risk factor for development of lung cancer.
• Passive exposure to tobacco smoke also can cause lung cancer.
• The two types of lung cancer, which grow and spread differently, are the small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC).
• The stage of lung cancer refers to the extent to which the cancer has spread in the body.
• Treatment of lung cancer can involve a combination of surgery, chemotherapy, and radiation therapy as well as newer experimental methods.
• The general prognosis of lung cancer is poor, with overall survival rates of about 16% at five years.
• Smoking cessation is the most important measure that can prevent the development of lung cancer.

What is lung cancer?

Cancer of the lung, like all cancers, results from an abnormality in the body's basic unit of life, the cell. Normally, the body maintains a system of checks and balances on cell growth so that cells divide to produce new cells only when new cells are needed. Disruption of this system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor.
Tumors can be benign or malignant; when we speak of "cancer," we are referring to those tumors that are malignant. Benign tumors usually can be removed and do not spread to other parts of the body. Malignant tumors, on the other hand, grow aggressively and invade other tissues of the body, allowing entry of tumor cells into the bloodstream or lymphatic system and then to other sites in the body. This process of spread is termed metastasis; the areas of tumor growth at these distant sites are called metastases. Since lung cancer tends to spread or metastasize very early after it forms, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs -- particularly the adrenal glands, liver, brain, and bone -- are the most common sites for lung cancer metastasis.

How common is lung cancer?

Lung cancer is the most common cause of death due to cancer in both men and women throughout the world. The American Cancer Society estimated that 222,520 new cases of lung cancer in the U.S. will be diagnosed and 157,300 deaths due to lung cancer would occur in 2010. According to the U.S. National Cancer Institute, approximately one out of every 14 men and women in the U.S. will be diagnosed with cancer of the lung at some point in their lifetime.
Lung cancer is predominantly a disease of the elderly; almost 70% of people diagnosed with lung cancer are over 65 years of age, while less than 3% of lung cancers occur in people under 45 years of age.
Lung cancer was not common prior to the 1930s but increased dramatically over the following decades as tobacco smoking increased. In many developing countries, the incidence of lung cancer is beginning to fall following public education about the dangers of cigarette smoking and the introduction of effective smoking-cessation programs. Nevertheless, lung cancer remains among the most common types of cancers in both men and women worldwide. In the U.S., lung cancer has surpassed breast cancer as the most common cause of cancer-related deaths in women.

What causes lung cancer?

Smoking
The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked and the time over which smoking has occurred; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history. While the risk of lung cancer is increased with even a 10-pack-year smoking history, those with 30-pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.
Pipe and cigar smoking also can cause lung cancer, although the risk is not as high as with cigarette smoking. Thus, while someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.
Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking.
Passive smoking
Passive smoking or the inhalation of tobacco smoke by nonsmokers who share living or working quarters with smokers, also is an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with nonsmokers who do not reside with a smoker. An estimated 3,000 lung cancer deaths that occur each year in the U.S. are attributable to passive smoking.
Asbestos fibers
Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past as both thermal and acoustic insulation. Today, asbestos use is limited or banned in many countries, including the U.S. Both lung cancer and mesothelioma (cancer of the pleura of the lung as well as of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos. Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in workers exposed to asbestos. Asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, but asbestos workers who smoke have a risk that is fifty- to ninetyfold greater than nonsmokers.
Radon gas
Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. Uranium decays to form products, including radon, that emit a type of ionizing radiation. Radon gas is a known cause of lung cancer, with an estimated 12% of lung-cancer deaths attributable to radon gas, or about 20,000 lung-cancer-related deaths annually in the U.S., making radon the second leading cause of lung cancer in the U.S. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings. The U.S. Environmental Protection Agency estimates that one out of every 15 homes in the U.S. contains dangerous levels of radon gas. Radon gas is invisible and odorless, but it can be detected with simple test kits.
Familial predisposition
While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and nonsmoking relatives of those who have had lung cancer than in the general population. Recently, the largest genetic study of lung cancer ever conducted, involving over 10,000 people from 18 countries and led by the International Agency for Research on Cancer (IARC), identified a small region in the genome (DNA) that contains genes that appear to confer an increased susceptibility to lung cancer in smokers. The specific genes, located the q arm of chromosome 15, code for proteins that interact with nicotine and other tobacco toxins (nicotinic acetylcholine receptor genes).
Lung diseases
The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with an increased risk (four- to sixfold the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded.
Prior history of lung cancer
Survivors of lung cancer have a greater risk of developing a second lung cancer than the general population has of developing a first lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs, see below), the risk for development of second lung cancers approaches 6% per year.
Air pollution
Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk for the development of lung cancer similar to that of passive smoking.

 

What are the types of lung cancer?

Lung cancers, also known as bronchogenic carcinomas, are broadly classified into two types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways and may have different treatment options, so a distinction between these two types is important.
SCLC comprise about 20% of lung cancers and are the most aggressive and rapidly growing of all lung cancers. SCLC are strongly related to cigarette smoking, with only 1% of these tumors occurring in nonsmokers. SCLC metastasize rapidly to many sites within the body and are most often discovered after they have spread extensively. Referring to a specific cell appearance often seen when examining samples of SCLC under the microscope, these cancers are sometimes called oat cell carcinomas.
NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC can be divided into three main types that are named based upon the type of cells found in the tumor:

• Adenocarcinomas are the most commonly seen type of NSCLC in the U.S. and comprise up to 50% of NSCLC. While adenocarcinomas are associated with smoking, like other lung cancers, this type is observed as well in nonsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that frequently develops at multiple sites in the lungs and spreads along the preexisting alveolar walls.
• Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi.
• Large cell carcinomas, sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC.
• Mixtures of different types of NSCLC are also seen.

Other types of cancers can arise in the lung; these types are much less common than NSCLC and SCLC and together comprise only 5%-10% of lung cancers:

• Bronchial carcinoids account for up to 5% of lung cancers. These tumors are generally small (3 cm-4 cm or less) when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumors can metastasize, and a small proportion of these tumors secrete hormone-like substances that may cause specific symptoms related to the hormone being produced. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection.
• Cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response can rarely occur in the lung.

As discussed previously, metastatic cancers from other primary tumors in the body are often found in the lung. Tumors from anywhere in the body may spread to the lungs either through the bloodstream, through the lymphatic system, or directly from nearby organs. Metastatic tumors are most often multiple, scattered throughout the lung, and concentrated in the peripheral rather than central areas of the lung.

What are lung cancer symptoms and signs?

 

Symptoms of lung cancer are varied depending upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. A person with lung cancer may have the following kinds of symptoms:

• No symptoms: In up to 25% of people who get lung cancer, the cancer is first discovered on a routine chest X-ray or CT scan as a solitary small mass sometimes called a coin lesion, since on a two-dimensional X-ray or CT scan, the round tumor looks like a coin. These patients with small, single masses often report no symptoms at the time the cancer is discovered.
• Symptoms related to the cancer: The growth of the cancer and invasion of lung tissues and surrounding tissue may interfere with breathing, leading to symptoms such as cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). If the cancer has invaded nerves, for example, it may cause shoulder pain that travels down the outside of the arm (called Pancoast's syndrome) or paralysis of the vocal cords leading to hoarseness. Invasion of the esophagus may lead to difficulty swallowing (dysphagia). If a large airway is obstructed, collapse of a portion of the lung may occur and cause infections (abscesses, pneumonia) in the obstructed area.
• Symptoms related to metastasis: Lung cancer that has spread to the bones may produce excruciating pain at the sites of bone involvement. Cancer that has spread to the brain may cause a number of neurologic symptoms that may include blurred vision, headaches, seizures, or symptoms of stroke such as weakness or loss of sensation in parts of the body.
• Paraneoplastic symptoms: Lung cancers frequently are accompanied by symptoms that result from production of hormone-like substances by the tumor cells. These paraneoplastic syndromes occur most commonly with SCLC but may be seen with any tumor type. A common paraneoplastic syndrome associated with SCLC is the production of a hormone called adrenocorticotrophic hormone (ACTH) by the cancer cells, leading to oversecretion of the hormone cortisol by the adrenal glands (Cushing's syndrome). The most frequent paraneoplastic syndrome seen with NSCLC is the production of a substance similar to parathyroid hormone, resulting in elevated levels of calcium in the bloodstream.
• Nonspecific symptoms: Nonspecific symptoms seen with many cancers, including lung cancers, include weight loss, weakness, and fatigue. Psychological symptoms such as depression and mood changes are also common.

When should one consult a doctor?
One should consult a health-care provider if he or she develops the symptoms associated with lung cancer, in particular, if they have

• a new persistent cough or worsening of an existing chronic cough
,
• blood in the sputum,
• persistent bronchitis or repeated respiratory infections
,
• chest pain
,
• unexplained weight loss and/or fatigue
,
• breathing difficulties such as shortness of breath or wheezing

What is the treatment for lung cancer?

Treatment for lung cancer can involve surgical removal of the cancer, chemotherapy, or radiation therapy, as well as combinations of these treatments. The decision about which treatments will be appropriate for a given individual must take into account the location and extent of the tumor as well as the overall health status of the patient.
As with other cancers, therapy may be prescribed that is intended to be curative (removal or eradication of a cancer) or palliative (measures that are unable to cure a cancer but can reduce pain and suffering). More than one type of therapy may be prescribed. In such cases, the therapy that is added to enhance the effects of the primary therapy is referred to as adjuvant therapy. An example of adjuvant therapy is chemotherapy or radiotherapy administered after surgical removal of a tumor in an attempt to kill any tumor cells that remain following surgery.
Surgery: Surgical removal of the tumor is generally performed for limited-stage (stage I or sometimes stage II) NSCLC and is the treatment of choice for cancer that has not spread beyond the lung. About 10%-35% of lung cancers can be removed surgically, but removal does not always result in a cure, since the tumors may already have spread and can recur at a later time. Among people who have an isolated, slow-growing lung cancer removed, 25%-40% are still alive five years after diagnosis. It is important to note that although a tumor may be anatomically suitable for resection, surgery may not be possible if the person has other serious conditions (such as severe heart or lung disease) that would limit their ability to survive an operation. Surgery is less often performed with SCLC than with NSCLC because these tumors are less likely to be localized to one area that can be removed.
The surgical procedure chosen depends upon the size and location of the tumor. Surgeons must open the chest wall and may perform a wedge resection of the lung (removal of a portion of one lobe), a lobectomy (removal of one lobe), or a pneumonectomy (removal of an entire lung). Sometimes lymph nodes in the region of the lungs also are removed (lymphadenectomy). Surgery for lung cancer is a major surgical procedure that requires general anesthesia, hospitalization, and follow-up care for weeks to months. Following the surgical procedure, patients may experience difficulty breathing, shortness of breath, pain, and weakness. The risks of surgery include complications due to bleeding, infection, and complications of general anesthesia.
Radiation: Radiation therapy may be employed as a treatment for both NSCLC and SCLC. Radiation therapy uses high-energy X-rays or other types of radiation to kill dividing cancer cells. Radiation therapy may be given as curative therapy, palliative therapy (using lower doses of radiation than with curative therapy), or as adjuvant therapy in combination with surgery or chemotherapy. The radiation is either delivered externally, by using a machine that directs radiation toward the cancer, or internally through placement of radioactive substances in sealed containers within the area of the body where the tumor is localized. Brachytherapy is a term used to describe the use of a small pellet of radioactive material placed directly into the cancer or into the airway next to the cancer. This is usually done through a bronchoscope.
Radiation therapy can be given if a person refuses surgery, if a tumor has spread to areas such as the lymph nodes or trachea making surgical removal impossible, or if a person has other conditions that make them too ill to undergo major surgery. Radiation therapy generally only shrinks a tumor or limits its growth when given as a sole therapy, yet in 10%-15% of people it leads to long-term remission and palliation of the cancer. Combining radiation therapy with chemotherapy can further prolong survival when chemotherapy is administered. External radiation therapy can generally be carried out on an outpatient basis, while internal radiation therapy requires a brief hospitalization. A person who has severe lung disease in addition to a lung cancer may not be able to receive radiotherapy to the lung since the radiation can further decrease function of the lungs. A type of external radiation therapy called the "gamma knife" is sometimes used to treat single brain metastases. In this procedure, multiple beams of radiation coming from different directions are focused on the tumor over a few minutes to hours while the head is held in place by a rigid frame. This reduces the dose of radiation that is received by noncancerous tissues.
For external radiation therapy, a process called simulation is necessary prior to treatment. Using CT scans, computers, and precise measurements, simulation maps out the exact location where the radiation will be delivered, called the treatment field or port. This process usually takes 30 minutes to two hours. The external radiation treatment itself generally is done four or five days a week for several weeks.
Radiation therapy does not carry the risks of major surgery, but it can have unpleasant side effects, including fatigue and lack of energy. A reduced white blood cell count (rendering a person more susceptible to infection) and low blood platelet levels (making blood clotting more difficult and resulting in excessive bleeding) also can occur with radiation therapy. If the digestive organs are in the field exposed to radiation, patients may experience nausea, vomiting, or diarrhea. Radiation therapy can irritate the skin in the area that is treated, but this irritation generally improves with time after treatment has ended.
Chemotherapy: Both NSCLC and SCLC may be treated with chemotherapy. Chemotherapy refers to the administration of drugs that stop the growth of cancer cells by killing them or preventing them from dividing. Chemotherapy may be given alone, as an adjuvant to surgical therapy, or in combination with radiotherapy. While a number of chemotherapeutic drugs have been developed, the class of drugs known as the platinum-based drugs have been the most effective in treatment of lung cancers.
Chemotherapy is the treatment of choice for most SCLC, since these tumors are generally widespread in the body when they are diagnosed. Only half of people who have SCLC survive for four months without chemotherapy. With chemotherapy, their survival time is increased up to four- to fivefold. Chemotherapy alone is not particularly effective in treating NSCLC, but when NSCLC has metastasized, it can prolong survival in many cases.
Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments usually are given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles. Unfortunately, the drugs used in chemotherapy also kill normally dividing cells in the body, resulting in unpleasant side effects. Damage to blood cells can result in increased susceptibility to infections and difficulties with blood clotting (bleeding or bruising easily). Other side effects include fatigue, weight loss, hair loss, nausea, vomiting, diarrhea, and mouth sores. The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.
Prophylactic brain radiation: SCLC often spreads to the brain. Sometimes people with SCLC that is responding well to treatment are treated with radiation therapy to the head to treat very early spread to the brain (called micrometastasis) that is not yet detectable with CT or MRI scans and has not yet produced symptoms. Brain radiation therapy can cause short-term memory problems, fatigue, nausea, and other side effects.
Treatment of recurrence: Lung cancer that has returned following treatment with surgery, chemotherapy, and/or radiation therapy is referred to as recurrent or relapsed. If a recurrent cancer is confined to one site in the lung, it may be treated with surgery. Recurrent tumors generally do not respond to the chemotherapeutic drugs that were previously administered. Since platinum-based drugs are generally used in initial chemotherapy of lung cancers, these agents are not useful in most cases of recurrence. A type of chemotherapy referred to as second-line chemotherapy is used to treat recurrent cancers that have previously been treated with chemotherapy, and a number of second-line chemotherapeutic regimens have been proven effective at prolonging survival. People with recurrent lung cancer who are well enough to tolerate therapy also are good candidates for experimental therapies (see below), including clinical trials.
Targeted therapy: The drugs erlotinib (Tarceva) and gefitinib (Iressa) are so-called targeted drugs, which may be used in certain patients with NSCLC who are no longer responding to chemotherapy. Targeted therapy drugs more specifically target cancer cells, resulting in less damage to normal cells than general chemotherapeutic agents. Erlotinib and gefitinib target a protein called the epidermal growth factor receptor (EGFR) that is important in promoting the division of cells. This protein is found at abnormally high levels on the surface of some types of cancer cells, including many cases of non-small cell lung cancer.
Other attempts at targeted therapy include drugs known as antiangiogenesis drugs, which block the development of new blood vessels within a cancer. Without adequate blood vessels to supply oxygen-carrying blood, the cancer cells will die. The antiangiogenic drug bevacizumab (Avastin) has also been found to prolong survival in advanced lung cancer when it is added to the standard chemotherapy regimen. Bevacizumab is given intravenously every two to three weeks. However, since this drug may cause bleeding, it is not appropriate for use in patients who are coughing up blood, if the lung cancer has spread to the brain, or in people who are receiving anticoagulation therapy ("blood thinner" medications). Bevacizumab also is not used in cases of squamous cell cancer because it leads to bleeding from this type of lung cancer.
Cetuximab is an antibody that binds to the epidermal growth factor receptor (EGFR).. In patients with NSCLC whose tumors have been shown to express the EGFR by immunohistochemical analysis, the addition of cetuximab may be considered for some patients.
Photodynamic therapy (PDT): One newer therapy used for different types and stages of lung cancer (as well as some other cancers) is photodynamic therapy. In photodynamic treatment, a photosynthesizing agent (such as a porphyrin, a naturally occurring substance in the body) is injected into the bloodstream a few hours prior to surgery. During this time, the agent is taken up in rapidly growing cells such as cancer cells. A procedure then follows in which the physician applies a certain wavelength of light through a handheld wand directly to the site of the cancer and surrounding tissues. The energy from the light activates the photosensitizing agent, causing the production of a toxin that destroys the tumor cells. PDT has the advantages that it can precisely target the location of the cancer, is less invasive than surgery, and can be repeated at the same site if necessary. The drawbacks of PDT are that it is only useful in treating cancers that can be reached with a light source and is not suitable for treatment of extensive cancers. The U.S. Food and Drug Administration (FDA) has approved the photosensitizing agent called porfimer sodium (Photofrin) for use in PDT to treat or relieve the symptoms of esophageal cancer and non-small cell lung cancer. Further research is ongoing to determine the effectiveness of PDT in other types of lung cancer.
Radiofrequency ablation (RFA): Radiofrequency ablation is being studied as an alternative to surgery, particularly in cases of early stage lung cancer. In this type of treatment, a needle is inserted through the skin into the cancer, usually under guidance by CT scanning. Radiofrequency (electrical) energy is then transmitted to the tip of the needle where it produces heat in the tissues, killing the cancerous tissue and closing small blood vessels that supply the cancer. RFA usually is not painful and has been approved by the U.S. Food and Drug Administration for the treatment of certain cancers, including lung cancers. Studies have shown that this treatment can prolong survival similarly to surgery when used to treat early stages of lung cancer but without the risks of major surgery and the prolonged recovery time associated with major surgical procedures.
Experimental therapies: Since no therapy is currently available that is absolutely effective in treating lung cancer, patients may be offered a number of new therapies that are still in the experimental stage, meaning that doctors do not yet have enough information to decide whether these therapies should become accepted forms of treatment for lung cancer. New drugs or new combinations of drugs are tested in so-called clinical trials, which are studies that evaluate the effectiveness of new medications in comparison with those treatments already in widespread use. Experimental treatments known as immunotherapies are being studied that involve the use of vaccine-related therapies or other therapies that attempt to utilize the body's immune system to fight cancer cells.

 

Introdution to steroids

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone and the anti-inflammatory drug dexamethasone.
The core of steroids is composed of twenty carbon atoms bonded together that take the form of four fused rings: three cyclohexane rings (designated as rings A, B and C in the figure to the right) and one cyclopentane ring (the D ring). The steroids vary by the functional groups attached to this four-ring core and by the oxidation state of the rings. Sterols are special forms of steroids, with a hydroxyl group at position-3 and a skeleton derived from cholestane.^[1]
Hundreds of distinct steroids are found in plants, animals and fungi. All steroids are made in cells either from the sterols lanosterol (animals and fungi) or from cycloartenol (plants). Both lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.^[2]

Structure

Steroids are a class of organic compounds with a chemical structure that contains the core of gonane or a skeleton derived therefrom. Usually, methyl groups are present at the carbons C-10 and C-13 – an alkyl side-chain at carbon C-17 may also be present.

The basic skeleton of a steroid, with standard stereo orientation. R is a side-chain at C-17.

Cholesterol. This steroid is the precursor to other steroids in the steroidogenesis.

Gonane is the simplest possible steroid and is composed of seventeen carbon atoms, bonded together to form four fused rings. The three cyclohexane rings (designated as rings A, B, and C in the figure below) form the skeleton of phenanthrene; ring D has a cyclopentane structure. Hence, together they are called cyclopentaphenanthrene.^[3]

Numbering of rings and of carbon atoms in gonane, the simplest possible steroid.

The structure of cholestane, one of the comparatively simpler steroids.

The more complex structure of cholic acid, a bile acid.

Commonly, steroids have a methyl group at the carbons C-10 and C-13 and an alkyl side chain at carbon C-17. Further, they vary by the configuration of the side chain, the number of additional methyl groups, and the functional groups attached to the rings. For example, sterols have a hydroxyl group attached at position C-3.
Some exemplary steroids with their structures:

The anabolic steroid testosterone, the principal male sex hormone.

Progesterone, a steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis.

Medrogestone, a synthetic drug with similar effects as progesterone.

An example of functional groups is the hydroxyl group at C-3 common to sterols.

β-Sitosterol, a phytosterol showing the hydroxyl group at C-3.

 

7 benefits of regular physical activity

 Want to feel better, have more energy and perhaps even live longer? Look no further than exercise. The health benefits of regular exercise and physical activity are hard to ignore. And the benefits of exercise are yours for the taking, regardless of your age, sex or physical ability. Need more convincing to exercise? Check out these seven ways exercise can improve your life.

 

No. 1: Exercise controls weight

Exercise can help prevent excess weight gain or help maintain weight loss. When you engage in physical activity, you burn calories. The more intense the activity, the more calories you burn. You don't need to set aside large chunks of time for exercise to reap weight-loss benefits. If you can't do an actual workout, get more active throughout the day in simple ways — by taking the stairs instead of the elevator or revving up your household chores.

No. 2: Exercise combats health conditions and diseases

Worried about heart disease? Hoping to prevent high blood pressure? No matter what your current weight, being active boosts high-density lipoprotein (HDL), or "good," cholesterol and decreases unhealthy triglycerides. This one-two punch keeps your blood flowing smoothly, which decreases your risk of cardiovascular diseases. In fact, regular physical activity can help you prevent or manage a wide range of health problems and concerns, including stroke, metabolic syndrome, type 2 diabetes, depression, certain types of cancer, arthritis and falls.

No. 3: Exercise improves mood

Need an emotional lift? Or need to blow off some steam after a stressful day? A workout at the gym or a brisk 30-minute walk can help. Physical activity stimulates various brain chemicals that may leave you feeling happier and more relaxed. You may also feel better about your appearance and yourself when you exercise regularly, which can boost your confidence and improve your self-esteem.

No. 4: Exercise boosts energy

Winded by grocery shopping or household chores? Regular physical activity can improve your muscle strength and boost your endurance. Exercise and physical activity deliver oxygen and nutrients to your tissues and help your cardiovascular system work more efficiently. And when your heart and lungs work more efficiently, you have more energy to go about your daily chores.

No. 5: Exercise promotes better sleep

Struggling to fall asleep? Or to stay asleep? Regular physical activity can help you fall asleep faster and deepen your sleep. Just don't exercise too close to bedtime, or you may be too energized to fall asleep.

No. 6: Exercise puts the spark back into your sex life

Do you feel too tired or too out of shape to enjoy physical intimacy? Regular physical activity can leave you feeling energized and looking better, which may have a positive effect on your sex life. But there's more to it than that. Regular physical activity can lead to enhanced arousal for women. And men who exercise regularly are less likely to have problems with erectile dysfunction than are men who don't exercise.

No. 7: Exercise can be fun

Exercise and physical activity can be a fun way to spend some time. It gives you a chance to unwind, enjoy the outdoors or simply engage in activities that make you happy. Physical activity can also help you connect with family or friends in a fun social setting. So, take a dance class, hit the hiking trails or join a soccer team. Find a physical activity you enjoy, and just do it. If you get bored, try something new.

The bottom line on exercise

Exercise and physical activity are a great way to feel better, gain health benefits and have fun. As a general goal, aim for at least 30 minutes of physical activity every day. If you want to lose weight or meet specific fitness goals, you may need to exercise more. Remember to check with your doctor before starting a new exercise program, especially if you have any health concerns.

Typhoid fever

Typhoid fever, also known simply as typhoid,^[1] is a common worldwide bacterial disease transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica enterica, serovar Typhi.^[2]
The disease has received various names, such as gastric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever and pythogenic fever. The name typhoid means "resembling typhus" and comes from the neuropsychiatric symptoms common to typhoid and typhus.^[3] Despite this similarity of their names, typhoid fever and typhus are distinct diseases and are caused by different species of bacteria.^[4]
The impact of this disease fell sharply in the developed world with the application of 20th-century sanitation techniques.^{[citation needed]}

Signs and symptoms

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. Over the course of these stages, the patient becomes exhausted and emaciated.^[5]
In the first week, the temperature rises slowly, and fever fluctuations are seen with relative bradycardia, malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. There is a decrease in the number of circulating white blood cells (leukopenia) with eosinopenia and relative lymphocytosis; blood cultures are positive for Salmonella typhi or paratyphi. The Widal test is negative in the first week.^{[citation needed]}
In the second week of the infection, the patient lies prostrate with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. There are rhonchi in lung bases. The abdomen is distended and painful in the right lower quadrant, where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green, comparable to pea soup, with a characteristic smell. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transaminases. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage. (The major symptom of this fever is that the fever usually rises in the afternoon up to the first and second week.)
In the third week of typhoid fever, a number of complications can occur:

• Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually not fatal.
• Intestinal perforation in the distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
• Encephalitis
• Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.
• Metastatic abscesses, cholecystitis, endocarditis and osteitis

The fever is still very high and oscillates very little over 24 hours. Dehydration ensues, and the patient is delirious (typhoid state). One third of affected individuals develop a macular rash on the trunk.
By the end of third week, the fever starts subsiding (defervescence). This carries on into the fourth and final week.

 

Transmission

The bacterium that causes typhoid fever may be spread through poor hygiene habits and public sanitation conditions, and sometimes also by flying insects feeding on feces. Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling spread of the disease. According to statistics from the United States Centers for Disease Control and Prevention (CDC), the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S.A.

Cystic fibrosis

It has been hypothesized that cystic fibrosis may have risen to its present levels (1 in 2,500 in the UK) due to the heterozygous advantage that it confers against typhoid fever.^[6] The CFTR protein is present in both the lungs and the intestinal epithelium, and the mutant cystic fibrosis form of the CFTR protein prevents entry of the typhoid bacterium into the body through the intestinal epithelium. However, the heterozygous advantage hypothesis was proposed in one review in which the author himself writes, "Although cellular/molecular evidence presently is not available for this hypothesis, the CF mutation may be one of several mutations that have spread in European populations because they increased resistance to infectious diseases." Since no molecular experimental evidence has been presented in support of this theory, this theory is not accepted by the majority of the scientific community.

Diagnosis

Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and cultures of the blood and stool.^[7]
The Widal test is time-consuming, and often, when a diagnosis is reached, it is too late to start an antibiotic regimen.
The term enteric fever is a collective term that refers to typhoid and paratyphoid.^[8]

 

Prevention

Sanitation and hygiene are the critical measures that can be taken to prevent typhoid. Typhoid does not affect animals, and therefore, transmission is only from human to human. Typhoid can only spread in environments where human feces or urine are able to come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid.
There are two vaccines licensed for use for the prevention of typhoid:^[9] the live, oral Ty21a vaccine (sold as Vivotif Berna) and the injectable Typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are 50% to 80% protective and are recommended for travellers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form. There exists an older, killed-whole-cell vaccine that is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has a higher rate of side effects (mainly pain and inflammation at the site of the injection).^[9]

Treatment

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.
Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin.^[8][10] Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice.^[11][12][13] Cefixime is a suitable oral alternative.^[14][15]
Typhoid fever, when properly treated, is not fatal in most cases. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology (Baron S et al.). Treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.^[16]
When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases.^[17] In some communities, however, case-fatality rates may reach as high as 47%.^{[citation needed]}

Surgery

Surgery is usually indicated in cases of intestinal perforation. Most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations.
If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is not always successful in eradicating the carrier state because of persisting hepatic infection.

Resistance

Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, and these agents have not been used as first–line treatment for almost twenty years.^{[citation needed]} Typhoid that is resistant to these agents is known as multidrug-resistant typhoid (MDR typhoid).
Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are therefore moving away from using ciprofloxacin as the first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. For these patients, the recommended first line treatment is ceftriaxone. It has also been suggested that azithromycin is better at treating typhoid in resistant populations than both fluoroquinolone drugs and ceftriaxone.^[10] Azithromycin significantly reduces relapse rates compared with ceftriaxone.
There is a separate problem with laboratory testing for reduced susceptibility to ciprofloxacin: current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analysis of 271 isolates showed that around 18% of isolates with a reduced susceptibility to ciprofloxacin (MIC 0.125–1.0 mg/l) would not be picked up by this method.^[18] It is not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent on disk testing and cannot test for MICs.

 

Epidemiology

 

Best Diet Foods For Men

Many ways to diet. Especially men, diet is an important thing for the health of the body. Best diet foods for men is necessary, in order to be successful diet and do not require a long time. Certainly must be balanced with exercise and enough sleep. Because if not, then the diet will fail. 

Best diet foods for men are greatly help men get a healthy diet. Because with a healthy diet, the diet will also be organized according to the needs of the body. It is necessary to consider what kinds of best diet foods for men are an important food needed by our bodies. Below are some examples of best diet foods for men that can be consumed daily :

1. Green vegetables

Green vegetables contain lots of antioxidants. Vegetables can neutralize free radicals in the brain. In addition, the vegetables could prevent the effects of aging on mental activity. Spinach and kale are examples of vegetables that are very helpful. Yes, kale and spinach are rich sources of vitamins A, C, K, calcium, and magnesium. Greens is perfect for us who are on a diet, because the greens are low in calories. cancer risk can be avoided because green vegetables low in fat, rich in folic acid, vitamin C.potassium, magnesium.

2. Nuts

Bean contains many nutrients needed by the body. Almonds and walnuts is one example peanuts are good for the diet.By consuming almonds, can burn fat as much as 18 percent compared with those not consuming almonds. Almonds contains 26% carbohydrate, vitamin E, unsaturated fatty acids that can lower cholesterol, vitamin B and potassium. Almonds also have benefits to strengthen the resilience of collapse, protecting the liver and anti-inflammatory.

3. Eggs  

Eggs as a source of protein. egg is able to maintain stamina while we do a healthy diet program. The scientists say that the protein content in the egg can make you feel full longer than eating protein in the cereal. One large egg contains 70 calories, 6 grams protein, 5 grams of fat, and 186 milligrams of cholesterol. Therefore, when we have breakfast, eat eggs better than rice. Due to consume eggs, hunger can persist longer, and diet will go smoothly.
Eating 2 eggs a day, enough to maintain a healthy body and heart.

4. Fruit 

Basically, all the fruit is healthy, but if we're on a diet there are some pieces that should be avoided because they contain high levels of sugar, and of course very detrimental. It could even ruin our diet. Fruits are good for diet: berries, cherries, apples, pears, peaches. These fruits contain a lot of fiber and antioxidants, and also has a low sugar content. Besides fruit and vegetable consumption in high quantities, it can also keep us from heart attacks and cancer.

That's some of the best diet foods for men that can be consumed every day. Besides, there are some other things that should be avoided. Among which avoid eating foods with saturated fat, eating lean meats, limiting sodium intake, and 3 servings of low-fat milk every day. Surely it must be balanced with regular exercise activities, adequate rest and stress management so that the body metabolism can be maintained.

8 Tips for Healthy, White Teeth

1. Go on a white-teeth diet.

If you're quaffing red wine and black tea, or smoking cigarettes or cigars, expect the results to show up as not-so-pearly whites. Other culprits to blame for dingy teeth include colas, gravies, and dark juices. Bottom line: If it's dark before you put it in your mouth, it will probably stain your teeth. Brush immediately after eating or drinking foods that stain teeth and use a good bleaching agent, either over-the-counter or in the dentist's office. For convenient teeth-cleaning action, eat an apple.

2. Chuck your toothbrush...

...or change the head of your electric toothbrush at least every two to three months. Otherwise, you're just transferring bacteria to your mouth. According to Beverly Hills dentist Harold Katz, D.D.S., the best way to brush is by placing your toothbrush at a 45-degree angle against your gums and gently moving it in a circular motion, rather than a back-and-forth motion. Grip the toothbrush like a pencil so you won't scrub too hard.

3. Clean your tongue.

Use a tongue scraper every morning to remove tongue plaque and freshen your breath. One major cause of bad breath is the buildup of bacteria on the tongue, which a daily tongue scraping will help banish. Plus, using a tongue scraper is more effective than brushing your tongue with a toothbrush, says Dr. Katz.

4. Eat 'detergent' foods.

Foods that are firm or crisp help clean teeth as they're eaten. We already mentioned apples (otherwise known as nature's toothbrush); other choices include raw carrots, celery, and popcorn. For best results, make 'detergent' foods the final food you eat in your meal if you know you won't be able to brush your teeth right after eating.

5. Gargle with apple cider vinegar.

Do this in the morning and then brush as usual. The vinegar helps help remove stains, whiten teeth, and kill bacteria in your mouth and gums.

6. Brush your teeth with baking soda once a week

This will remove stains and whiten your teeth. Use it just as you would toothpaste. You can also use salt as an alternative toothpaste. Just be sure to spit it out so it doesn't count as sodium intake! Also, if your gums start to feel raw, switch to brushing with salt every other day.

7. Stay fresh.

To check the freshness of your breath, lick your palm and smell it while it's still wet. If you smell something, it’s time for a sugar-free breath mint. Shopping for mouthwash? Make sure it is alcohol-free. Most over-the-counter mouthwashes have too much alcohol, which can dry out the tissues in your mouth, making them more susceptible to bacteria.

8. Practice flossing with your eyes shut.

If you can floss without having to guide your work with a mirror, you can floss in your car, at your desk, while in bed, and before important meetings. In which case, buy several packages of floss and scatter them in your car, your desk, your purse, your briefcase, your nightstand.

Dengue Fever

Dengue fever , also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.
Dengue is transmitted by several species of mosquito within the genus Aedes, principally A. aegypti. The virus has four different types; infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. As there is no commercially available vaccine, prevention is sought by reducing the habitat and the number of mosquitoes and limiting exposure to bites.
Treatment of acute dengue is supportive, using either oral or intravenous rehydration for mild or moderate disease, and intravenous fluids and blood transfusion for more severe cases. The incidence of dengue fever has increased dramatically since the 1960s, with around 50–100 million people infected yearly. Early descriptions of the condition date from 1779, and its viral cause and the transmission were elucidated in the early 20th century. Dengue has become a global problem since the Second World War and is endemic in more than 110 countries. Apart from eliminating the mosquitoes, work is ongoing on a vaccine, as well as medication targeted directly at the virus.

Typically, people infected with dengue virus are asymptomatic (80%) or only have mild symptoms such as an uncomplicated fever.^[1][2][3] Others have more severe illness (5%), and in a small proportion it is life-threatening.^[1][3] The incubation period (time between exposure and onset of symptoms) ranges from 3–14 days, but most often it is 4–7 days.^[4] Therefore, travelers returning from endemic areas are unlikely to have dengue if fever or other symptoms start more than 14 days after arriving home.^[5] Children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea)^[6] and have a greater risk of severe complications,^[5][7] though initial symptoms are generally mild but include high fever.^[7]

Most cases in the United States occur in people who contracted the infection while traveling abroad. But the risk is increasing for people living along the Texas-Mexico border and in other parts of the southern United States. In 2009, an outbreak of dengue fever was identified in Key West, Fla.

Dengue fever is transmitted by the bite of an Aedes mosquito infected with a dengue virus. The mosquito becomes infected when it bites a person with dengue virus in their blood. It can’t be spread directly from one person to another person.

Symptoms of Dengue Fever

Symptoms, which usually begin four to six days after infection and last for up to 10 days, may include

• Sudden, high fever
• Severe headaches
• Pain behind the eyes
• Severe joint and muscle pain
• Nausea
• Vomiting
• Skin rash, which appears three to four days after the onset of fever
• Mild bleeding (such a nose bleed, bleeding gums, or easy bruising)

Sometimes symptoms are mild and can be mistaken for those of the flu or another viral infection. Younger children and people who have never had the infection before tend to have milder cases than older children and adults. However, serious problems can develop. These include dengue hemorrhagic fever, a rare complication characterized by high fever, damage to lymph and blood vessels, bleeding from the nose and gums, enlargement of the liver, and failure of the circulatory system. The symptoms may progress to massive bleeding, shock, and death. This is called dengue shock syndrome (DSS).

People with weakened immune systems as well as those with a second or subsequent dengue infection are believed to be at greater risk for developing dengue hemorrhagic fever.

Diagnosing Dengue Fever

Doctors can diagnose dengue infection with a blood test to check for the virus or antibodies to it. If you become sick after traveling to a tropical area, let your doctor know. This will allow your doctor to evaluate the possibility that your symptoms were caused by a dengue infection.

Treatment for Dengue Fever

There is no specific medicine to treat dengue infection. If you think you may have dengue fever, you should use pain relievers with acetaminophen and avoid medicines with aspirin, which could worsen bleeding. You should also rest, drink plenty of fluids, and see your doctor. If you start to feel worse in the first 24 hours after your fever goes down, you should get to a hospital immediately to be checked for complications.

Clinical course

The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. The alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains.^[1][9] The course of infection is divided into three phases: febrile, critical, and recovery.^[8]
The febrile phase involves high fever, potentially over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days.^[8][9] Nausea and vomiting may also occur.^[7] A rash occurs in 50–80% of those with symptoms^[9][10] in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash.^[10][11] Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point,^[8] as may some mild bleeding from the mucous membranes of the mouth and nose.^[5][9] The fever itself is classically biphasic in nature, breaking and then returning for one or two days, although there is wide variation in how often this pattern actually happens.^[11][12]
In some people, the disease proceeds to a critical phase around the time fever resolves^[7] and typically lasts one to two days.^[8] During this phase there may be significant fluid accumulation in the chest and abdominal cavity due to increased capillary permeability and leakage. This leads to depletion of fluid from the circulation and decreased blood supply to vital organs.^[8] During this phase, organ dysfunction and severe bleeding, typically from the gastrointestinal tract, may occur.^[5][8] Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue,^[5] however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk.^[5][13] This critical phase, while rare, occurs relatively more commonly in children and young adults.^[7]
The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream.^[8] This usually lasts two to three days.^[5] The improvement is often striking, and can be accompanied with severe itching and a slow heart rate.^[5][8] Another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by peeling of the skin.^[7] During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures.^[5] A feeling of fatigue may last for weeks in adults.^[7]

Laboratory tests

The diagnosis of dengue fever may be confirmed by microbiological laboratory testing.^[28][34] This can be done by virus isolation in cell cultures, nucleic acid detection by PCR, viral antigen detection (such as for NS1) or specific antibodies (serology).^[14][31] Virus isolation and nucleic acid detection are more accurate than antigen detection, but these tests are not widely available due to their greater cost.^[31] Detection of NS1 during the febrile phase of a primary infection may be greater than 90% however is only 60–80% in subsequent infections.^[7] All tests may be negative in the early stages of the disease.^[5][14] PCR and viral antigen detection are more accurate in the first seven days.^[7] In 2012 a PCR test was introduced that can run on equipment used to diagnose influenza; this is likely to improve access to PCR-based diagnosis.^[35]
These laboratory tests are only of diagnostic value during the acute phase of the illness with the exception of serology. Tests for dengue virus-specific antibodies, types IgG and IgM, can be useful in confirming a diagnosis in the later stages of the infection. Both IgG and IgM are produced after 5–7 days. The highest levels (titres) of IgM are detected following a primary infection, but IgM is also produced in reinfection. IgM becomes undetectable 30–90 days after a primary infection, but earlier following re-infections. IgG, by contrast, remains detectable for over 60 years and, in the absence of symptoms, is a useful indicator of past infection. After a primary infection IgG reaches peak levels in the blood after 14–21 days. In subsequent re-infections, levels peak earlier and the titres are usually higher. Both IgG and IgM provide protective immunity to the infecting serotype of the virus.^[9][14][36] The laboratory test for IgG and IgM antibodies can cross-react with other flaviviruses and may result in a false positive after recent infections or vaccinations with yellow fever virus or Japanese encephalitis.^[7] The detection of IgG alone is not considered diagnostic unless blood samples are collected 14 days apart and a greater than fourfold increase in levels of specific IgG is detected. In a person with symptoms, the detection of IgM is considered diagnostic.^[36]