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Therapies

Photodynamic therapy

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Description:
Photodynamic therapy (PDT), sometimes called photochemotherapy, is a form of phototherapy using nontoxic light-sensitive compounds that are exposed selectively to light, whereupon they become toxic to targeted malignant and other diseased cells (phototoxicity). PDT has proven ability to kill microbial cells, including bacteria, fungi and viruses. PDT is popularly used in treating acne. It is used clinically to treat a wide range of medical conditions, including wet age-related macular degeneration and malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic.

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Most modern PDT applications involve three key components: a photosensitizer, a light source and tissue oxygen. The combination of these three components leads to the chemical destruction of any tissues which have either selectively taken up the photosensitizer or have been locally exposed to light. The wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce reactive oxygen species. These reactive oxygen species generated through PDT are free radicals (Type I PDT) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen (Type II PDT). In understanding the mechanism of PDT it is important to distinguish it from other light-based and laser therapies such as laser wound healing and rejuvenation, or intense pulsed light hair removal, which do not require a photosensitizer.

Why it is done:
Photodynamic therapy (PDT) was first used in 1905 for the treatment of skin cancers. Since then, it has been further developed and used for the treatment of many kinds of cancers (lung, colon, etc.) as well as certain kinds of blindness. PDT combines a drug (called a photosensitizer) that is preferentially absorbed by certain kinds of cells and a special light source. When used together, the photosensitizer and the light destroy the targeted cells. More recently, however, PDT has been used for photorejuvenation, wrinkles, discoloration, visible veins, and acne. When used for these conditions, the photosensitizer is applied to the face and then the skin is exposed to a light source. Rapidly growing cells, oil glands, and other structures in the skin absorb the photosensitizer and are destroyed by a reaction caused by the light. Cosmetic improvement in wrinkling, age spots, and visible veins has been documented after PDT treatment.

It is a new advance in facial rejuvenation and there are currently different methods in use. For example some physicians use blue light, red light, or intense pulse light. The photosensitizer is applied to the skin and is left on for a variable period of time. The skin is then exposed to the light source and the photosensitizer is then removed. Reported side effects include transient burning, stinging, swelling, and redness. Side effects are variable depending on what is being treated, how long the photosensitizer is left on, and which light source is used. No long-term studies have been performed to evaluate long term side effects.
Procedure:
In order to achieve the selective destruction of the target area using PDT while leaving normal tissues untouched, either the photosensitizer can be applied locally to the target area, or photosensitive targets can be locally excited with light. For instance, in the treatment of skin conditions, including acne, psoriasis, and also skin cancers, the photosensitizer can be applied topically and locally excited by a light source. In the local treatment of internal tissues and cancers, after photosensitizers have been administered intravenously, light can be delivered to the target area using endoscopes and fiber optic catheters....CLICK & SEE

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Photosensitizers can also target many viral and microbial species, including HIV and MRSA. Using PDT, pathogens present in samples of blood and bone marrow can be decontaminated before the samples are used further for transfusions or transplants. PDT can also eradicate a wide variety of pathogens of the skin and of the oral cavities. Given the seriousness that drug resistant pathogens have now become, there is increasing research into PDT as a new antimicrobial therapy.

Photosensitizers:
In air and tissue, molecular oxygen occurs in a triplet state, whereas almost all other molecules are in a singlet state. Reactions between these are forbidden by quantum mechanics, thus oxygen is relatively non-reactive at physiological conditions. A photosensitizer is a chemical compound that can be promoted to an excited state upon absorption light and undergo intersystem crossing with oxygen to produce singlet oxygen. This species rapidly attacks any organic compounds it encounters, thus being highly cytotoxic. It is rapidly eliminated: in cells, the average lifetime is 3 µs.[5]

A wide array of photosensitizers for PDT exist. They can be divided into porphyrins, chlorophylls and dyes. Some examples include aminolevulinic acid (ALA), Silicon Phthalocyanine Pc 4, m-tetrahydroxyphenylchlorin (mTHPC), and mono-L-aspartyl chlorin e6 (NPe6).

Several photosensitizers are commercially available for clinical use, such as Allumera, Photofrin, Visudyne, Levulan, Foscan, Metvix, Hexvix, Cysview, and Laserphyrin, with others in development, e.g. Antrin, Photochlor, Photosens, Photrex, Lumacan, Cevira, Visonac, BF-200 ALA. Amphinex. Also Azadipyrromethenes.

Although these photosensitizers can be used for wildly different treatments, they all aim to achieve certain characteristics:

*High absorption at long wavelengths

*Tissue is much more transparent at longer wavelengths (~700–850 nm). Absorbing at longer wavelengths would allow the light to penetrate deeper,[8] and allow the treatment of larger tumors.

*High singlet oxygen quantum yield

*Low photobleaching to prevent degradation of the photosensitizer

*Natural fluorescence

*Many optical dosimetry techniques, such as fluorescence spectroscopy, depend on the drug being naturally fluorescent[10]

*High chemical stability

*Low dark toxicity

*The photosensitizer should not be harmful to the target tissue until the treatment beam is applied.

*Preferential uptake in target tissue

The major difference between different types of photosensitizers is in the parts of the cell that they target. Unlike in radiation therapy, where damage is done by targeting cell DNA, most photosensitizers target other cell structures. For example, mTHPC has been shown to localize in the nuclear envelope and do its damage there. In contrast, ALA has been found to localize in the mitochondria and Methylene Blue in the lysosomes.

To allow treatment of deeper tumours some researchers are using internal chemiluminescence to activate the photosensitiser.

PUVA therapy is using psoralen as photosensitiser and UVA ultraviolet as light source, but this form of therapy is usually classified as a separate form of therapy from photodynamic therapy.

Targeted PDT:
Some photosensitisers naturally accumulate in the endothelial cells of vascular tissue allowing ‘vascular targeted’ PDT, but there is also research to target the photosensitiser to the tumour (usually by linking it to antibodies or antibody fragments). It is currently only in pre-clinical studies.

Applications:
Compared to normal tissues, most types of cancers are especially active in both the uptake and accumulation of photosensitizers agents, which makes cancers especially vulnerable to PDT. Since photosensitizers can also have a high affinity for vascular endothelial cells.

Usage in acne:
PDT is currently in clinical trials to be used as a treatment for severe acne. Initial results have shown for it to be effective as a treatment only for severe acne, though some question whether it is better than existing acne treatments. The treatment causes severe redness and moderate to severe pain and burning sensation. A phase II trial, while it showed improvement occurred, failed to show improved response compared to the blue/violet light alone
Advantages:
There are several advantages of photodynamic therapy over other forms of facial rejuvenation. For example, PDT is less destructive (and therefore less painful) than many of the deeper peels and lasers. There is also minimal recovery time. It is also a proven technique for the treatment of precancerous lesions. Thus, depending on the technique used, there may be an additional benefit of preventing skin cancer.

Disadvantages:
The disadvantage of photodynamic therapy is that it is new. Long-term side effects are unknown, and the benefits are not as well studied. For example, PDT is not known how long the benefits last.

Although PDT is a promising new therapy, you need to discuss the risks, benefits, and alternatives with your physician to decide if PDT is right for you.
Modern development of PDT in Russia:
Of all the nations beginning to use PDT in the late 20th century, the Russians were the quickest to advance its use clinically and to make many developments. One early Russian development was a new photosensitizer called Photogem which, like HpD, was derived from haematoporphyrin in 1990 by Professor Andrey F. Mironov and coworkers in Moscow. Photogem was approved by the Ministry of Health of Russia and tested clinically from February 1992 to 1996. A pronounced therapeutic effect was observed in 91 percent of the 1500 patients that underwent PDT using Photogem, with 62 percent having a total tumor resolution. Of the remaining patients, a further 29 percent had a partial tumor resolution, where the tumour at least halved in size. In those patients that had been diagnosed early, 92 percent of the patients showed complete resolution of the tumour.

Around this time, Russian scientists also collaborated with NASA medical scientists who were looking at the use of LEDs as more suitable light sources, compared to lasers, for PDT applications.

Modern development of PDT in Asia:
PDT has also seen considerably development in Asia. Since 1990, the Chinese have been developing specialist clinical expertise with PDT using their own domestically produced photosensitizers, derived from Haematoporphyrin, and light sources. PDT in China is especially notable for the technical skill of specialists in effecting resolution of difficult to reach tumours
Resources:
http://en.wikipedia.org/wiki/Photodynamic_therapy
http://www.dermanetwork.org/information/pdt.asp

Categories
Ailmemts & Remedies

Yellow Fever

TEM micrograph: Multiple yellow fever virions ...
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Definition:
Yellow fever (also called yellow jack, black vomit or sometimes American Plague) is an acute viral disease. It is an important cause of hemorrhagic illness in many African and South American countries despite existence of an effective vaccine. The yellow refers to the jaundice symptoms that affect some patients.It is a viral infection transmitted by mosquitoes.

Yellow fever is a viral hemorrhagic fever caused by the yellow fever virus. The yellow fever virus is a single-stranded enveloped virus that belongs to the flavivirus group. The disease can result in mild symptoms or severe illness and death (mortality rate 5-70%). Yellow fever derives its name from the yellowing of the skin and whites of the eyes (jaundice) that occur in some people infected with the virus. Jaundice is caused by the presence of bile pigment (bilirubin) in the bloodstream and results from damage to liver cells (hepatocytes) during severe infection.…click & see

The yellow fever virus infects mainly monkeys and humans: monkeys are the animal reservoir. Infection is transmitted from human to human, monkey to monkey, monkey to human, and human to monkey by daytime-biting mosquitos. Several species of Aedes and Haemoagogus mosquitos can serve as vectors, transmitting the virus during a blood meal.

Three types of transmission cycles exist for yellow fever: sylvatic (jungle), intermediate and urban. Although all three transmission cycles occur in Africa, only sylvatic and urban transmission cycles occur in South America.

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Sylvatic yellow fever (monkey to human)

* Occurs in monkeys infected by wild mosquitos in tropical rainforests

* Infected monkeys pass the virus to mosquitos during feeding
* Infected wild mosquitos bite humans entering the rainforest (accidental infection)

Intermediate yellow fever (monkey to human; human to monkey)
* Small-scale epidemics that occur in humid or semi-humid grasslands of Africa
* Separate villages experience simultaneous infections transmitted by semi-domestic mosquitos that infect both monkey and human hosts
* Most common type of outbreak in Africa

Urban yellow fever (human to human)

* Large epidemics occurring when the virus is introduced into high human population areas by migrants
* Domestic mosquitos of one species (Aedes aegypti) transmit the virus from person to person
* Monkeys are not involved in transmission
* Outbreaks spread from one source to cover a wide area

Yellow fever has been a source of several devastating epidemics. Yellow fever epidemics broke out in the 1700s in Italy, France, Spain, and England. 300,000 people are believed to have died from yellow fever in Spain during the 19th century. French soldiers were attacked by yellow fever during the 1802 Haitian Revolution; more than half of the army perished from the disease. Outbreaks followed by thousands of deaths occurred periodically in other Western Hemisphere locations until research, which included human volunteers (some of whom died), led to an understanding of the method of transmission to humans (primarily by mosquitos) and development of a vaccine and other preventive efforts in the early 20th century.

Despite the costly and sacrificial breakthrough research by Cuban physician Carlos Finlay, American physician Walter Reed, and many others over 100 years ago, unvaccinated populations in many developing nations in Africa and Central and South America continue to be at risk. As of 2001, the World Health Organization (WHO) estimates that yellow fever causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations.

Causes :-
Yellow fever is caused by a small virus that is spread by the bite of mosquitoes. This disease is common in South America and in sub-Saharan Africa.

……………You may click to see pictures of  mosquitoes  causing yellow fever.….

Anyone can get yellow fever, but the elderly have a higher risk of severe infection. If a person is bitten by an infected mosquito, symptoms usually develop 3 – 6 days later.

Yellow fever has three stages:
1.Early stage: Headache, muscle aches, fever, loss of appetite, vomiting, and jaundice are common. After approximately 3 – 4 days, often symptoms go away briefly (remission).

2.Period of remission: After 3 – 4 days, fever and other symptoms go away. Most people will recover at this stage, but others may move onto the third, most dangerous stage (intoxication stage) within 24 hours.

3.Period of intoxication: Multi-organ dysfunction occurs. This includes liver and kidney failure, bleeding disorders/hemorrhage, and brain dysfunction including delirium, seizures, coma, shock, and death.

Symptoms :-
*Arrhythmias, heart dysfunction
*Bleeding (may progress to hemorrhage)
*Coma
*Decreased urination
*Delirium
*Fever
*Headache
*Jaundice
*Muscle aches (myalgia)
*Red eyes, face, tongue
*Seizures
*Vomiting
*Vomiting blood

Although viral replication begins in cells at the site of the mosquito bite, symptoms of infection are not usually noted for a period of three to six days when the acute phase of infection presents. Acute yellow fever infection is characterized by high fever, muscle pain, backache, headache, shivers, loss of appetite, nausea and/or vomiting. Most people infected improve after three to four days.

However, within 24 hours of the disappearance of symptoms, up to 15% of those infected enter a toxic phase during which fever resumes, and the yellow fever virus quickly spreads to the kidneys, lymph nodes, spleen, bone marrow and liver. Liver invasion of one of the last stages to occur: as the liver is increasingly damaged, patients develop jaundice as bilirubin is released from damaged liver cells, experience abdominal pain and vomiting, and develop coagulopathies (inability of the blood to clot) characterized by bleeding from the mouth, nose, eyes and stomach, and presence of blood in vomit and stool. Up to 50% of people who enter the toxic phase die within two weeks of infection.

Diagnosis:-
Yellow fever may be difficult to diagnose, especially during the early stages, and may be confused with malaria, typhoid, other hemorrhagic fevers (dengue, Rift Valley, Venezuelan, Bolivian, Argentine, Lassa, Crimean-Congo, Marburg and Ebola), rickettsial infection, leptospirosis, viral hepatitis, other causes of liver failure and toxic hepatitis (e.g. carbon-tetrachloride poisoning).

Exams and Tests
A person with advanced yellow fever may show signs of liver failure, renal failure, and shock.

If you have symptoms of yellow fever, tell your doctor if you have traveled to areas where the disease is known to thrive. Blood tests can confirm the diagnosis.

Treatment :-

There is no specific treatment for yellow fever. Treatment for symptoms can include:

*Blood products for severe bleeding
*Dialysis for kidney failure
*Fluids through a vein (intravenous fluids)

The treatment for yellow fever is supportive: control of fever, fluids to treat dehydration, and intensive support related to organ damage.

The World Health Organization estimates 200,000 cases of yellow fever per year with approximately 30,000 deaths.

CLICK TO READ ..>: Early sign of yellow fever could lead to new treatment

Prognosis: :-

Yellow fever ranges in severity. Severe infections with internal bleeding and fever (hemorrhagic fever) are deadly in up to half of cases.

Historical reports have claimed a mortality rate of between 1 in 17 (5.8%) and 1 in 3 (33%). CDC has claimed that case-fatality rates from severe disease range from 15% to more than 50%. The WHO factsheet on yellow fever, updated in 2001, states that 15% of patients enter a “toxic phase” and that half of that number die within ten to fourteen days, with the other half recovering

Possible Complications :-

*Coma
*Death
*Disseminated intravascular coagulation (DIC)
*Kidney failure
*Liver failure
*Parotitis
*Secondary bacterial infections
*Shock

Prevention :-

If you will be traveling to an area where yellow fever is common:

*Sleep in screened housing
*Use mosquito repellents
*Wear clothing that fully covers your body
*There is an effective vaccine against yellow fever. Ask your doctor at least 10 – 14 days before traveling if you should be *vaccinated against yellow fever.

In 1937, Max Theiler, working at the Rockefeller Foundation, developed a safe and highly efficacious vaccine for yellow fever that gives a ten-year or more immunity from the virus. The vaccine consists of a live, but attenuated, virus called 17D. The 17D vaccine has been used commercially since the 1950s. The mechanisms of attenuation and immunogenicity for the 17D strain are not known. However, this vaccine is very safe, with few adverse reactions having been reported and millions of doses administered, and highly effective with over 90% of vaccinees developing a measurable immune response after the first dose.

click to see the picture

Although the vaccine is considered safe, there are risks involved. The majority of adverse reactions to the 17D vaccine result from allergic reaction to the eggs in which the vaccine is grown. Persons with a known egg allergy should discuss this with their physician prior to vaccination. In addition, there is a small risk of neurologic disease and encephalitis, particularly in individuals with compromised immune systems and very young children. The 17D vaccine is contraindicated in infants, pregnant women, and anyone with a diminished immune capacity, including those taking immunosuppressant drugs.

According to the travel clinic at the University of Utah Hospital, the vaccine presents an increased risk of adverse reaction in adults aged 60 and older, with the risk increasing again after age 65, and again after age 70. The reaction is capable of producing multiple organ failure and should be evaluated carefully by a qualified health professional before being administered to the elderly.

Finally, there is a very small risk of more severe yellow fever-like disease associated with the vaccine. This reaction occurs in 1~3 vaccinees per million doses administered. This reaction, called YEL-AVD, causes a fairly severe disease closely resembling yellow fever caused by virulent strains of the virus. The risk factor/s for YEL-AVD are not known, although it has been suggested that it may be genetic. The 2`-5` oligoadenylate synthetase (OAS) component of the innate immune response has been shown to be particularly important in protection from Flavivirus infection. In at least one case of YEL-AVD, the patient was found to have an allelic mutation in a single nucleotide polymorphism (SNP) of the OAS gene. People most at risk of contracting the virus should be vaccinated. Woodcutters working in tropical areas should be particularly targeted for vaccination. Insecticides, protective clothing, and screening of houses are helpful, but not always sufficient for mosquito control; people should always use an insecticide spray while in certain areas. In affected areas, mosquito control methods have proven effective in decreasing the number of cases.

Recent studies have noted the increase in the number of areas affected by a number of mosquito-borne viral infections and have called for further research and funding for vaccines

Current research:-
In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective early treatment of many pathological features of the disease. Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in target organs (liver and spleen), prevented hepatocellular steatosis, and normalized alanine aminotransferase (a liver damage marker) levels. The results of this study suggest that ribavirin may be effective in the early treatment of yellow fever, and that its mechanism of action in reducing liver pathology in yellow fever virus infection may be similar to that observed with ribavirin in the treatment of hepatitis C, a virus related to yellow fever. Because ribavirin had failed to improve survival in a virulent primate (rhesus) model of yellow fever infection, it had been previously discounted as a possible therapy.

In 2007, the World Community Grid launched a project whereby computer modelling of the yellow fever virus (and related viruses), thousands of small molecules are screened for their potential anti-viral properties in fighting yellow fever. This is the first project to utilize computer simulations in seeking out medicines to directly attack the virus once a person is infected. This is a distributed process project similar to SETI@Home where the general public downloads the World Community Grid agent and the program (along with thousands of other users) screens thousands of molecules while their computer would be otherwise idle. If the user needs to use the computer the program sleeps. There are several different projects running, including a similar one screening for anti-AIDS drugs. The project covering yellow fever is called “Discovering Dengue Drugs – Together.” The software and information about the project can be found at: World Community Grid web site

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.
Resources:
http://en.wikipedia.org/wiki/Yellow_fever
http://www.nlm.nih.gov/medlineplus/ency/article/001365.htm
http://microbiology.suite101.com/article.cfm/yellow_fever

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