One Drug, Many Targets: Is This The Future?

Potential molecular targets of the anti-HIV drug nelfinavir have been identified, and may explain why the drug is also effective as a cancer therapy. Findings will be published in the open-access journal PLoS Computational Biology on 28th April 2011.
Nelfinavir is a protease inhibitor that prevents replication of the HIV virus. It has also been found to have a positive effect on a number of solid tumor types but the mechanism of how the drug worked in humans was unclear. Researchers from the University of California San Diego and the City University of New York (CUNY) combined a wide array of computational techniques to investigate the molecular mechanisms underlying nelfinavir's observed anti-cancer effect and found that there are weak interactions with a multitude of molecular targets, rather than a strong interaction with a single target.
While drug molecules are designed to bind to targeted proteins in order to achieve a therapeutic effect, small drug molecules can also attach to off-target proteins with similar binding sites. The result may be unwanted side effects or, as in the case of nelfinavir, a secondary and positive effect. Philip E. Bourne, professor of pharmacology at UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, and his colleagues suggest that it is the collective effect of these weak interactions that leads to the clinical efficacy of nelfinavir.
The computational methods used by the researchers are a useful way of searching for potential drug targets: "Computer analysis allows us to search for other binding sites that match a particular drug-binding site - like looking for other locks that can be opened by the same key," said Lei Xie, associate professor at Hunter College, CUNY. However, it is a particularly complex route to validation of drug targets. Prof. Bourne adds "This is indeed challenging, but it is hard not to believe that this broad-based systems approach represents the future of drug discovery, at least as far as small-molecule drugs are concerned."
Funding: NIH, GM078596. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Source:Medicalnewstoday

Breast Reconstruction

Anatomy and Physiology:

A woman's breasts are composed of glandular tissue and ducts, fat, connective tissue, blood vessels, and lymph vessels. The glands produce and secrete milk for breastfeeding an infant.
Changes in the breast are common. A woman's breast tissue changes over the course of her lifetime. It also changes during her menstrual cycle or if she is taking hormones.
Treatments:
Breast reconstruction may be performed using one of three techniques: A breast implant filled with a salt solution, or saline, a tissue flap, in which skin and other tissue is transferred from another part of the body to build a new breast, a combination of a breast implant and a tissue flap.
Breast reconstruction can be done at the time of a mastectomy, known as immediate reconstruction, or after a period of time, known as delayed reconstruction. You should discuss the decision to proceed with immediate versus delayed reconstruction with your surgeons.
Not all women who undergo a mastectomy choose breast reconstruction. Some decide to wear a breast form, or prosthesis, inside their bra. Breast forms come in a variety of shapes, sizes, and materials such as foam, cotton, and silicone.
Procedure:
Preparations for breast reconstruction generally include: a complete physical exam, blood tests, Electrocardiogram mammogram.
In the days leading up to your procedure: Arrange for a ride to and from the hospital and for help at home as you recover. The night before, eat a light meal and do not eat or drink anything after midnight. If you regularly take medications, herbs, or dietary supplements, your doctor may recommend temporarily discontinuing them. Do not start taking any new medications, herbs, or dietary supplements before consulting your doctor. Additionally, you may be asked to shower with special antibacterial soap the morning of the procedure.
For breast reconstruction using an implant, your surgeon will first place a balloon expander beneath the chest wall and close up the skin with stitches. Over the next several weeks, your surgeon will add a salt solution to the expander, which will stretch the skin and other tissues in the area.
For women having immediate reconstruction, a tissue expander may not be necessary and the final implant can be placed at the time of the mastectomy. If a tissue expander is used, it is later removed and replaced with a permanent implant.
The two most common tissue flap procedures are transverse rectus abdominus muscle flap, or TRAM, and latissimus dorsi flap, which refers to a muscle in the upper back.
In a TRAM reconstruction technique called a pedicle flap, your surgeon will take the flap and slide it under the skin to the breast area. Your surgeon will then shape the tissue into a natural looking breast and sew it into place. The flap remains attached to the original blood supply. An implant may be added to enhance the shape of the breast.
In another TRAM technique called a free flap, your surgeon will remove the flap and reattach it to the blood vessels in the chest area. This procedure takes longer because blood vessels need to be reconnected in their new location. An implant may be added to enhance the shape of the breast.
In a latissimus dorsi flap procedure, your surgeon will take a flap from the upper back and slide the tissue around through a tunnel under the skin to the breast area. He or she will then shape the tissue into a natural-looking breast and sew it into place.
If your surgeon needs to cut blood vessels, which is a rare occurrence, he or she will reattach them in the chest area using a microscope. Because tissue from the upper back contains little excess fat, your surgeon will likely insert an implant as well.
Immediate breast reconstruction begins during a mastectomy. Delayed reconstruction starts later. In either case, many patients undergoing reconstruction will require additional surgery to: add a nipple and areola; revise the shape or size of the reconstructed breast; perform surgery on the opposite breast to make them appear even.
Risks and Benefits:
Possible complications of breast reconstruction include: bleeding, infection, hardening, rupturing, or leaking of the implant, abnormal scarring, painful and/or restricted arm motion, uneven appearance to the breasts, and/or lack of sensation.
Another potential disadvantage is that an implant makes it more difficult to detect cancer via a mammogram or breast self exam.
Breast reconstruction offers the following benefits: restores natural appearance of breast shape, reduces self-consciousness and improves self-esteem.
In breast reconstruction surgery, or any procedure, you and your doctor must carefully weigh the risks and benefits to determine whether it's the most appropriate treatment choice for you.
After the Procedure:
Immediately following surgery you: May have one or more drains temporarily left in place at your incision sites; will have some discomfort during the first few days, which usually responds to pain medication; will receive IV fluids for 1-2 days.
The length of your hospital stay will depend on the type of reconstruction procedure that you have. Patients who receive implants typically stay 1-2 days, while flap procedures require a stay of 3-6 days. Total recovery time also varies depending on type of procedure, but 4-6 weeks is average.
After your procedure, contact your doctor if you experience any of the following symptoms: fever or chills, redness, swelling, increasing pain, excessive bleeding, or discharge at the incision site, a feeling that the implants are hardening or leaking, nausea and/or vomiting that's uncontrolled with medications given by the hospital, cough, shortness of breath, or chest pain, pain or swelling in the feet, calves, or legs.

Anatomy Of The Breast

The breast consists of a mixture of:

• Fat
• Milk glands - lobules that secrete milk during pregnancy and breastfeeding
• Mammary ducts – canals that carry milk from the lobules to the nipple openings
• Fibrous connective tissue
• Nerves
• Blood vessels
• Lymph vessels – delicate vessels that collect lymph fluid from tissues and drain it back into the bloodstream
• Small amounts of muscle tissue

In the nipple to allow it to become erect in response to sexual stimulation or breastfeeding
Around the lobules to help squeeze milk into the ducts.
Key muscles support the breasts rom behind and underneath.
Breast size and shape is unique to each woman and is determined by heredity and body size. However, breast tissue changes throughout a woman’s lifetime depending on hormonal changes.
Breasts develop at puberty as hormones stimulate the system to form and enlarge lobules and ducts. Full development can occur any time between the ages of 12 and 19.
A woman’s monthly menstrual cycle causes breast granularity to change. Swelling and tenderness of both breasts may occur during the second half of the menstrual cycle. Cysts may grow and then shrink.
During pregnancy, the lobules multiply and begin to produce milk.
When a baby is born, milk is released into the ducts for breastfeeding (lactation).
During menopause the number of lobules decreases and those remaining shrink. A larger proportion of the breast is made up of fat so breast density decreases.