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Monday, September 8, 2014

Cancer Cells need Invadopadia for Metastasis

Posted by Prahallad Panda on 12:15 PM Comments

Spread and localization of cancer cells in a distant place from the place of origin (primary)  is called metastasis. Metastasis is responsible of most of deaths from cancer. This occurs mainly in three ways; 1) Local or contiguous spread, 2) through blood stream and 3) spread through lymphatics.

There has been a lot of interest to zero on the mechanism of metastasis of tumor cells. It is being increasingly evident that tumour cell migrate by formation of invadopodia. Invadopodias are small foot-like structures that enable the tumour cells to move in and out of the blood vessel by crawling through the extracellular matrix (ECM).
During intra-vascular migration, cancer cells take amoeboid movement and form protrusive structures identified as invadopodia and stick to certain places in the inner layer (endothelium) of the blood vessels. Invadopadias are enriched with MT1-MMP, cortactin, Tks4, and importantly Tks5, which are proteins and enzymes required for extracellular matrix (ECM) digestion; prerequisite for tunnel formation for migration of cells. Invadopodia release enzymes that degrade the ECM, while other protrusions pull the cancer cell along, much like a locomotive pulls a train.
The blackish part is cell and the grey part is matrix

This has been demonstrated by the researchers from Albert Einstein College of Medicine of Yeshiva University that there exists a signaling pathway in cancer cells that controls their ability to invade nearby tissues in a finely orchestrated manner.
The findings offer insights into the early molecular events involved in metastasis, the deadly spread of cancer cells from primary tumour to other parts of the body. The study was published in May, 2014 online edition of Nature Cell Biology.
A research article published in the PLOS One elucidate the mechanisms through in-vitro assays that mimic the process of cancer cell invasion through basement membrane or in the stroma.
In fact, to stop invadopodia formation may a way to stop metastasis.

Saturday, August 23, 2014

Physical Activity can be a Miracle Cure of Many Ailments

Posted by Prahallad Panda on 5:57 PM Comments

I saw in the office of a CEO (Chief Executive Officer), who has a standing desk for official works, like looking into files, writing replies and discussing with the officials. He is a very health conscious person. He walks everyday and plays badminton, when time permits. Apart from all of these physical activities, he prefers to work in standing desk.
Standing puts many muscles to work for, while sitting does not. Now-a-days, due to the very nature of job, many have become sedentary. Many are not able to complete 30 minutes of walk 4-5 times in a week. Added to it is the woo of sedentary life, poses more risk for diseases like obesity, diabetes and heart disease etc..

A sedentary person, or
A sedentary person, or "typical couch potato" (Photo credit: Wikipedia)

Some studies suggest that those who sit all day live around two years less than those who are more active. In a 2012 study by Harvard researchers published in the Lancet medical journal claimed that sitting down had caused more deaths globally than tobacco.
If a person sleeps for 7 hours a day and on a modern day job, he might be spending as much as 16 hours in sitting in his office and watching TV in residence. Even if, he walks for one hour a day, the sedentary life style for 16 hours may nullify the benefits. It is stressed that in addition to intense physical activity, one must also be active most of the time excluding sleep time.
Standing-up increases the heart rate by about ten beats a minute, which in turn burns an extra 0.7 calories a minute, or 50 an hour.

Graphite, on tan wove paper, laid down on comm...
Graphite, on tan wove paper, laid down on commercially prepared ivory wove card (Photo credit: Wikipedia)
Now, that doesn't sound like much, but it adds up to about 50 calories an hour. If you stand for three hours a day for five days that's around 750 calories burnt. Over the course of a year, it would be about 30,000 calories. In other words, it would be the equivalent of running about 10 marathons a year; just by standing up three or four hours in your day at work.
While standing, one alternates load on legs; muscles of thigh, back and abdomen also work to maintain a straight posture; consume calories. On the contrary, sitting may cause some stagnation in blood circulation.
This can be achieved by holding stand-up meetings, coffees or lunches or set aside a certain amount of time to work standing up.
Standing while you are working may seem rather odd, but it is a practice with a long tradition. Winston Churchill wrote while working at a special standing desk, as did Ernest Hemingway and Benjamin Franklin.
The evidence that standing up is good for you goes back to at least the 1950s when a study was done comparing bus conductors (who stand) with bus drivers (who don't). This study, published in the Lancet, showed that the bus conductors had around half the risk of developing heart disease of the bus drivers.
Prolonged sitting has been associated with a high incidence of back complaints, increased spinal intra-disc pressure build up, discomfort in the lower extremities and increased muscle loading of the neck.
However, neither static standing nor sitting is recommended. Each position has its advantages and disadvantages. Research indicates that constrained sitting or constrained standing are risk factors and that alternating work postures may be preferable. Alternation between two postures allows for increased rest intervals of specific body parts, and reduced potential for risk factors commonly associated with development of Musculo-skeletal disorder.
A different set of studies suggests that simple inactivity by itself may cause harm by altering the metabolism. It has been seen that simple sitting decreases the level of Lipoprotein Lipase (LPL), one of the critical enzymes that regulates the levels of triglycerides and HDL (high-density lipoprotein, good cholesterol). Level of triglycerides goes up and that of HDL goes down in such a situation. This enzyme is located in muscle and adipose tissue. In a decreased state, uptake of triglycerides decreases, that means, more is available in circulation to do harm. After just a few hours of inactivity, there occurs changes in the activity levels of over 100 genes.
It doesn’t matter, if you go running every morning, or you’re a regular at the gym. If you spend most of the rest of the day sitting — in your car, your office chair, on your sofa at home — you are putting yourself at increased risk of obesity, diabetes, heart disease, a variety of cancers and an early death. In other words, irrespective of whether you exercise vigorously, sitting for long periods is bad for you.
Let us stand up and work.


Sunday, July 20, 2014

Non-Alcoholic Fatty Liver Disease (NAFLD) and steatohepatitis (NASH) may lead to serious Liver Diseases.

Posted by Prahallad Panda on 11:23 AM Comments

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are are most common liver disease in western countries; now, the incidence is increasing in the Middle East, Far East, Africa, the Caribbean, and Latin America.
NAFLD and NASH represent a major global public health problem, which is pandemic and affects rich and poor countries alike.
NAFLD is a condition, where there is excessive accumulation of fat in the form of triglycerides (steatosis) in the liver.

Micrograph demonstrating marked (macrovesicula...
Micrograph demonstrating marked (macrovesicular) steatosis in non-alcoholic fatty liver disease. Masson's trichrome stain. (Photo credit: Wikipedia)
It has been found in a study that the prevalence of NAFLD has doubled during last 20 years, whereas the prevalence of other chronic liver diseases has remained stable or even decreased.
NAFLD may progress to NASH, where there occurs liver cell injury and inflammation in addition to the excessive fat accumulation.
Progression of NAFLD to NASH dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma.
The exact cause of NASH has not been elucidated, however it is most closely related to insulin resistance, obesity, and the metabolic syndrome. But, it not at all a rule that all patients with these conditions will lead to NAFLD/NASH, and vice-versa.
NAFLD and NASH are the diseases diagnosed by method of exclusion of other conditions. Not every person with fatty liver needs aggressive therapy.
Diet and exercise should be instituted for all patients. Patients with NASH or risk factors for NASH may additionally be treated with high dosages of Vitamin E or pentoxifylline, experimental therapy. These should only be tried in patients who fail to achieve a 5% to 10% weight reduction over 6 months to 1 year of successful lifestyle changes.
Bariatric surgery may be considered in patients in whom the above approaches fail, and it should be performed before the patient becomes cirrhotic.
Liver transplantation is successful in patients who meet the criteria for liver failure; however, NASH may recur after transplantation and is likely to be denied to patients with morbid obesity.
As a Clinician may not be able to diagnose NASH on the basis of clinical data alone, in a similar way the pathologist may not be able to document the histological lesions of steatohepatitis and reliably distinguish those of non-alcoholic origin from those of alcoholic origin.


Saturday, July 12, 2014

Sandalwood Scent Activate Olfactory Receptors in Skin to hasten wound healing

Posted by Prahallad Panda on 9:58 PM Comments

Skin can smell!
Skin cells can get excited by the fragrance from sandal wood and kick start wound healing; the researchers from Ruhr-Universität Bochum, Germany have discovered.

English: Glass vial containing Sandalwood (San...
English: Glass vial containing Sandalwood (Santalum album) Essential Oil (Photo credit: Wikipedia)

Not only nose is the site for Olfactory Receptors (OR) as popularly known, but also these receptors are housed in many other cells; spermatozoa, melanocytes and dendritic cells etc..
They have found several ORs in the skin cells called keratinocytes viz. OR6M1, OR11A1, OR6V1, OR5V1 and OR2AT4 using microarray and RT-PCR analyses.
Out of the host of olfactory receptors, OR2AT4 is of special interest for wound healing because activated OR2AT4 triggers the proliferation and migration of keratinocytes, which are the essential steps for re-epithelialization of the wounds.
Possibly this happens via calcium-dependant signalling pathway in primary keratinocytes induced by Sandalore and Brahmanol found in sandal wood oil.
Further down stream, the signaling cascade possibly activates the cAMP/PKA pathway or multiple pathways including EGFR to the phosphorylation of the MAP kinases Erk1/2 and p38, resulting the increased proliferation and migration of cells.
All the synthetic sandalwood molecules may not have the desired molecules to have the effect.


Saturday, June 28, 2014

Updated Recommendation for Testing of HIV 1 & 2 Infection

Posted by Prahallad Panda on 10:05 PM Comments

According to a press release in 2012, the total number of people living with HIV/AIDS in India is estimated at 21 lakhs in 2011. Children (<15 yrs) account for 7% of all infections, while 86% are in the age group of 15-49 years. Of all HIV infections, 39% (8.16 lakh) are among women.
An estimated 1.1 million persons in United States were living with human immunodeficiency virus (HIV) infection as of 2010, of whom an estimated 181,000 were unaware of their infection.

Approximately 49,000 new HIV diagnoses are reported to Centers for Disease Control (CDC) each year.As of 2009, an estimated 83 million adults aged 18 to 64 years reported they had been tested for HIV.
Accurate laboratory diagnosis of HIV is essential to identify persons who could benefit from treatment, to reassure persons who are uninfected, and to reduce HIV transmission.
HIV immunoassays based on different design principles are generally grouped into “generations”:  
  • 1st generation—All antigens used to bind HIV antibodies are from a lysate of HIV-1 viruses grown in cell culture. An indirect immunoassay format employs labeled antihuman IgG for detection of IgG antibodies. Significant specimen dilution is required to overcome cross-reactivity with cellular protein contaminants. Examples commercially available in the United States as of May 2014 include the HIV-1 Western blot and the HIV-1 IFA.  
  • 2nd generation—Synthetic peptide or recombinant protein antigens alone or combined with viral lysates are used to bind HIV antibodies. An indirect immunoassay format employs labeled antihuman IgG or protein A (which binds to IgG with high affinity for detection of IgG antibodies. Design of the specific antigenic epitopes improves sensitivity for HIV-1 group O and HIV-2; eliminating cellular antigens that contaminate viral lysates improves specificity by eliminating cross-reactivity with cellular proteins. Examples commercially available in the United States as of May 2014 include one HIV-1 enzyme immunoassay and six rapid HIV antibody tests.
  • 3rd generation—Synthetic peptide or recombinant protein antigens are used to bind HIV antibodies in an immunometric antigen sandwich format (HIV antibodies in the specimen bind to HIV antigens on the assay substrate and to antigens conjugated to indicator molecules). This allows detection of IgM and IgG antibodies. Lower sample dilutions and the ability to detect IgM antibodies (which are expressed before IgG antibodies) increase sensitivity during early seroconversion. Examples commercially available in the United States as of May 2014 include one HIV-1/HIV-2 enzyme immunoassay and two HIV-1/HIV-2 chemiluminescent immunoassays.
  • 4th generation—Synthetic peptide or recombinant protein antigens are used in the same antigen sandwich format as 3rd generation assays to detect IgM and IgG antibodies, and monoclonal antibodies are also included to detect p24 antigen. Inclusion of p24 antigen capture allows detection of HIV-1 infection before seroconversion. These assays (termed “combo” assays”) usually do not distinguish antibody reactivity from antigen reactivity. Examples commercially available in the United States as of May 2014 include one HIV-1/HIV-2 enzyme immunoassay, one HIV-1/HIV-2 chemiluminescent immunoassay, and one HIV-1/HIV-2 rapid test that uses separate indicators for antigen and antibody reactivity.
Immediately after HIV infection, low levels of HIV-1 RNA (ribonucleic acid) might be present
intermittently, but no viral markers are consistently detectable in plasma. Approximately 10
days after infection, HIV-1 RNA becomes detectable by Nucleic Acid Test (NAT) in plasma and quantities increase to very high levels.
Next, HIV-1 p24 antigen is expressed and quantities rise to levels that can be detected by 4th generation immunoassays within 4 to 10 days after the initial detection of HIV-1 RNA. However, p24 antigen detection is transient because, as antibodies begin to develop, they bind to the p24 antigen and form immune complexes that interfere with p24 assay detection unless the assay includes steps to disrupt the antigen-antibody complexes.immunoglobulin (Ig)M antibodies are expressed which can be detected by 3rd and 4th generation immunoassays 3 to 5 days after p24 antigen is first detectable, 10 to 13 days after the appearance of viral RNA.
Finally, IgG antibodies emerge and persist throughout the course of HIV infection. First and second generation immunoassays designed to detect only IgG antibodies exhibit considerable variability in their sensitivity during early infection, becoming reactive 18 to 38 days or more after the initial detection of viral RNA.

Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens 


 FDA approved Tests


Source: Centers for Disease Control and Prevention (CDC); Read more

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