Random Nature #166

Undesirable Glowing:  One of the things that CSI shows have taught us is that ultraviolet light can help us see things, like certain bodily fluids that are naturally fluorescent.  People can now buy portable UV lights (like this one) to check, for instance, the cleanliness of their motel room.  It makes an interesting tool for quality control. 

The bacterium Clostridium difficile (a relative of the one that causes botulism) is a common cause of diarrhea (previous blog here).  Add the right chemicals, and it can be made to glow under UV light.

Alfa's toilet inspectors smeared the UV lotion under the seats of 20 toilets and commodes being used by patients with diarrhoea at a hospital in Winnipeg. Seven of these patients had C. difficile infection, while 13 others did not. The toilets and commodes were tested every weekday for six months and checked using UV light to determine how well they had been cleaned. In addition, samples were taken from toilet surfaces to determine whether C difficile spores were present.

The UV marker revealed that the commodes for the seven patients isolated with C. difficile infections had not been properly cleaned 72% of the time. The toilets fared slightly better, with half of the samples taken showing no residual UV lotion after cleaning. The 13 patients not on isolation had much cleaner toilets, with only 14% glowing brightly under UV light. Further assessments showed that differences in toilet cleaning were “ward dependent” and since specific cleaners work on different wards, the results likely reflect characteristics of the individual cleaning staff.

More worryingly, C. difficile was still detected in 40% of samples taken from the cleanest toilets (i.e. those with no detectable UV marker). “This suggests that both the physical cleaning action as well as the disinfectant/cleaning agent were ineffective for killing and/or removing C. difficile from toilets,” notes Alfa.

Spores are harder to kill because they're designed to survive conditions that would otherwise kill the bacteria.  Worse still, hospitals in several nations (including the U.S.) have been struggling with a superbug version of C. difficile.  In the UK, it kills more people than MRSA.

Seeking Luminescent Feedback:  Researchers at Ohio State University were looking a better way to test of how potential cancer drugs--individually and in combination--impacted adult T-cell lymphoma and leukemia (ATLL).  This is a particularly difficult cancer for multiple reasons, including the following:

“We can inject these tumor cells into the abdomen of the mice and they will grow in the animals' lymph nodes,” explained Rosol, “but normally, you can't detect the extent of the animal's disease until the cancer is in its later stages.”   

Making the cancer cells luminesce on demand enables some rather precise feedback.      

...Rosol's team took a novel approach: They took a gene responsible for a firefly's glow and genetically inserted it into these tumor cells. That gene produces the enzyme luciferase in the insects which, when combined with another compound, luciferin, causes the firefly's distinctive glow.

The mice then received these genetically modified tumor cells and the researchers injected luciferin into the animals. Cancer cells containing the luciferase would combine with the luciferin and glow in the dark, giving the team a clear picture of the extent of disease inside the animal.

“We put these mice inside a blackened chamber with a digital camera and then took their pictures. The only light present would be the light emitted by the cancer cells,” Rosol said.

“We just measured the light that we could see coming out of the animal – the more light, the more tumor growth; the less light, less tumor.”

Here's another way to use luminescence in cancer treatment. 

A study was carried out by researchers of the University of Michigan Health System who inserted the gene which is responsible for the firefly glow-producing molecule into mice with cancer. The researchers kept the molecule from producing the telltale glow until cells started to die in response to cancer treatment given to the mice. Researchers then used a highly sensitive camera to detect the glow in the mice as the cancer cells were destroyed by the drugs which was being tested.

Researchers concluded that the results of the study indicated that the glow molecule could aid in faster testing of new drugs for cancer, blood diseases, autoimmune disorders, heart attack damage and others, as these molecules could provide real time information about the effectiveness of new medications.

Some day with radiation treatments, maybe we'll nuke 'em 'til they don't glow.

Lumenoscopy:  The human papillomavirus (HPV) doesn't just help cause cervical cancer.

It has long been recognized that oral cancer kills one American every hour, but even health experts thought the primary causes were smoking and heavy drinking, and the main victims were older men. Fresh research and a new FDA-approved technology are putting a whole new light on all-too-common, and all-too-deadly oral cancer, indicating new causes and much younger male and female victims.

Johns Hopkins researchers, writing in the February 1 issue of the Journal of Clinical Oncology, reported that the sexually transmitted HPV virus, a major cause of cervical cancer, causes as many cancers of the upper throat as tobacco and alcohol combined. Oral sex is the likely method of transmission. The researchers say HPV is the primary cause of some 5,600 cancers per year in the tonsils, lower tongue and upper throat. And, they found, the incidence rate for HPV-related oral cancers among males has been rising steadily for three decades. Co-author Dr. Maura Gillison told the Associated Press, "If current trends continue, within the next 10 years there may be more oral cancers in the United States caused by HPV than tobacco or alcohol."

Here's a description of the technology.

ViziLite Plus with TBlue is an oral lesion identification and marking system that is used as an adjunct to the conventional head and neck examination. It is comprised of a chemiluminescent light source (ViziLite) to improve the identification of lesions and a blue phenothiazine dye to mark those lesions identified by ViziLite. ViziLitePlus with TBlue is designed to be used in a patient population at increased risk for oral cancer. ...

In clinical trials involving 13,000 female patients, abnormal squamous epithelium in the cervical complex appears distinctly white after washing the cervix with a dilute acetic acid solution and viewed under chemiluminescent light (Speculite).  Similarly, examination of the oral cavity under chemiluminescent light (ViziLite) after rinsing with a dilute acetic acid solution, abnormal squamous epithelium tissue will appear distinctly white. Lumenoscopy has demonstrated in numerous studies to improve the ability to visualize mucosal lesions and initially identify clinically suspicious lesions.

The rinse (flavored vinegar) and ViziLite glowstick combine to make tiny lesions a bit easier to see. 

TBlue is a patented, pharmaceutical-grade toluidine blue-based metachromatic dye.  It is used to further evaluate and closely monitor changes in ViziLite-identified lesions.  It has been proposed that living cells will differentially accumulate toluidine blue based on parameters related to metabolic activity.  TBlue packaged in an easy to use 3-swab system, provides the deep blue staining that allows ViziLite-identified lesions to be seen clearly under normal light.

The FDA approved the ViziLite in 2001 and the TBlue oral lesion marking system in 2005.  But, the American Dental Association still doesn't endorse the test.  This article helps explain why the ADA denied its seal of approval.  Nonetheless, the ease of testing more people has brought to light the increasing prevalence of oral cancer in groups who weren't thought to be at high risk.