Tuesday, November 26, 2013

Antibiotic crisis and molecular medicine

Antibacterial/Antibiotic:
In 1928 that Alexander Fleming observed antibiosis against bacteria by a fungus of the genus Penicillium. Fleming postulated the effect was mediated by an antibacterial compound named penicillin, and that its antibacterial properties could be exploited for chemotherapy.
Sir Alexander Fleming, 1952
Photograph courtesy of Associated Press

The discovery of such a powerful antibiotic was unprecedented, and the development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety. These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942.


 


Antibiotics and World War 2:

Penicillin, the first natural antibiotic discovered by Alexander Fleming in 1928

1939 - coinciding with the start of world war 2,
commercially manufactured antibiotics universally and effectively used to treat wounds and ulcers during WW2.

As the first antibiotic discovered was penicillin. Penicillin was first widely used on large numbers of patients in World War II (1939–45). 


The wonder drug:
Penicillin was first tested for military use in the spring of 1943, with pilot studies on soldiers with chronic bacterial infections in Bushnell General Hospital in Utah and Halloran General Hospital in New York. By autumn, doctors were using antibiotic in combat zones, where it was limited to American and Allied military and to patients with life-threatening infections.
The first U.S. wounded to directly benefit from the drug were the flight crews of the Eighth Air Force stationed in Britain. Rationing was necessary, as a single infection could require 2 million or more units of the drug (single ampoules sealed glass vessels holding solutions
for hypodermic injection contained 100,000 units). During the war, the armed forces received 85 percent of the nation's production, which amounted to 231 billion units in 1943. With the implementation of successful mass-production techniques, 1,633 billion units were produced in 1944 and 7,952 billion units in 1945. Penicillin became the war's "wonder drug," and its remarkable medical effects on infectious disease made World War II different from any previous war. (http://www.lib.niu.edu/2001/iht810139.html)

Antibiotic crisis:
Antibiotics, the wonder drug of the 20th century, may become irrelevant in the very near future and as so called Superbugs develops immunity to medication.
 Overuse of antibiotics may lead to superbug epidemic much sooner than is commonly thought.
A crisis looms. In the very near rapidly approaching future, the wonder drugs of the 20th century, antibiotics, may cease to be useful.

Antibiotics become a thing of the past: revolutionary research:
Just this month, researchers have announced a new treatment that will combat antibiotic resistance. This new synthesis, called PPMO *, offers a fundamentally different attack on bacterial infections.
PPMO are synthetic analogs of DNA or RNA that have the ability to silence the expression of specific genes. 

The mechanism that PPMOs use to kill bacteria is revolutionary,” said Bruce Geller, a professor of microbiology in the OSU College of Science and lead author on the study. “They can be synthesized to target almost any gene, and in that way avoid the development of antibiotic resistance and the negative impacts sometimes associated with broad-spectrum antibiotics.

 

“Molecular medicine,”# Geller said, “is the way of the future.” PPMOs specifically target the underlying genes of a bacterium, whereas conventional antibiotics disrupt its cellular function with broader, often unwanted consequences.

#(The molecular medicine perspective emphasizes cellular and molecular phenomena and interventions rather than the previous conceptual and observational focus on patients and their organs.)

*PPMO: peptide-conjugated phosphorodiamidate morpholino oligomer

The findings were published this month in the Journal of Infectious Diseases, by researchers from OSU, the University of Texas Southwestern Medical Center, and Sarepta, Inc., a Corvallis, Ore., firm.

Reference:1.Geller, Bruce L., Marshall-Batty, Kimberly, Schnell, Frederick J., Mcknight, Mattie M., Iversen, Patrick L. and David E. Greenberg. Gene-Silencing Antisense Oligomers Inhibit Acinetobacter Growth In Vitro and In Vivo. Journal of Infectious Diseases, October 2013

Thankfully consulted and shared above references from: http://nimblepixie.com/?p=8038 http://jid.oxfordjournals.org/content/early/2013/09/30/infdis.jit460.abstract   http://www.lib.niu.edu/2001/iht810139.html http://en.wikipedia.org


 



Thursday, November 21, 2013

Links between culture, health and happiness

The Impact of Cultural Engagement and Sports Participation on Health and Satisfaction with Life

A survey in Scotland has found that people who engage in culture are more likely to report good health.
Flag of Scotland
picture credit:
http://www.wikipedia.org
Participation in culture is significantly associated with good health and high life satisfaction in Scotland, according to the latest research. A detailed study by Scottish Government analysts of the impact on health of both culture and sport, based on data from the Scottish Household Survey 2011, confirms for the first time that participating in culture or attending cultural places or events has a positive impact on the nation’s health and life satisfaction.
The report, Healthy Attendance: The Impact of Cultural Engagement and Sports Participation on Health and Satisfaction with life in Scotland 2013, identifies a positive link with wellbeing even when other factors including age, economic status, income, area deprivation, education qualification, disability or long-standing illness and smoking are accounted for.

thankfully shared from
http://www.scotland.gov.uk/Publications/Recent

thankfully shared from
http://www.scotland.gov.uk/Publications/Recent
thankfully shared from
http://www.scotland.gov.uk/Publications/Recent
thankfully shared from
http://www.scotland.gov.uk/Publications/Recent
thankfully shared from
http://www.scotland.gov.uk/Publications/Recent


Key findings show:

  • Those who attended a cultural place or event in the previous 12 months were almost 60 per cent more likely to report good health compared to those who did not.
  • Those who participated in a creative or cultural activity in the previous 12 months were 38 per cent more likely to report good health compared to those who did not.
  • Those who visited a library and those who visited a museum were almost 20 per cent more likely to report good health than those who had not.
  • Those who visited a theatre were almost 25 per cent more likely to report good health than those who did not.
  • Those who participated in dance were 62 per cent more likely to report good health than those who did not.
  • Those who read for pleasure were 33 per cent more likely to report good health than those who did not.
The research follows data from the 2010 Scottish Household Survey that shows that people who are encouraged to participate in cultural activity as children are more likely to continue to do so into adulthood.

The survey involved nearly 10,000 respondents. 
reference courtesy:
http://www.scotland.gov.uk/Resource/0043/00430649.pdf
http://www.enterprise-europe-scotland.com
http://www.scotland.gov.uk
http://www.heraldscotland.com
http://new.a-n.co.uk
http://www.modernghana.com

Monday, November 11, 2013

Chronic stress alters gene activity in immune cells and oxidative stress detection tools

Chronic stress' effects can be traced to your genes

Researchers say repeated stress that triggers the sympathetic nervous system can lead to inflammation that is linked to many health problems.

A bad boss can cripple your immune system
 "So what this suggests is that if you're working for a really bad boss over a long period of time, that experience may play out at the level of gene expression in your immune system."
Last Updated: Wednesday, November 06, 2013, 16:02
(http://zeenews.india.com/news/health/health-news/chronic-stress-effects-can-be-traced-to-your-genes_24897.html)
http://www.health24.com/Mental-Health/
Stress/News/Effects-of-chronic-stress-can-
be-traced-to-genes-20131106
Washington: A new study has showed that chronic stress alters gene activity in immune cells 
before they reach the bloodstream.
With these changes, 
the cells are primed to fight an infection or trauma that doesn't actually exist, 
leading to an overabundance of the inflammation that is linked to many health problems.

Ohio State University scientists made and their colleagues from other institutions, testing blood samples from humans living in poor socioeconomic conditions, found that similarly primed immune cells were present in these chronically stressed people as well.
Co-lead author John Sheridan, professor of oral biology in the College of Dentistry and associate director of Ohio State's Institute for Behavioral Medicine Research (IBMR),sa di that the cells share many of the same characteristics in terms of their response to stress.
He said that there is a stress-induced alteration in the bone marrow in both our mouse model and in chronically stressed humans that selects for a cell that's going to be pro-inflammatory.
Sheridan and colleagues have been studying the same mouse model for a decade to reveal how chronic stress - and specifically stress associated with social defeat - changes the brain and body in ways that affect behavior and health.
The mice are repeatedly subjected to stress that might resemble a person's response to persistent life stressors. In this model, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours at a time.
This elicits a "fight or flight" response in the resident mice as they are repeatedly defeated by the intruder.
Under normal conditions, the bone marrow in animals and humans is making and releasing billions of red blood cells every day, as well as a variety of white blood cells that constitute the immune system.
In this work, the researchers compared cells circulating in the blood of mice that had experienced repeated social defeat to cells from control mice that were not stressed. The stressed mice had an average fourfold increase in the frequency of immune cells in their blood and spleen compared to the normal mice.

 #The study has been published in the journal Proceedings of the National Academy of Sciences.
#This work was supported by the National Institutes of Health; the Mind, Body, Brain and Health Initiative of the John D. and Catherine T. MacArthur Foundation; the British Columbia Ministry of Child and Family Development via the Human Early Learning Partnership; and the Allergy, Genes and Environment Research Network.
Additional co-authors are Erica Sloan of UCLA and the Monash Institute of Pharmaceutical Sciences in Australia; Michael Bailey (associate professor of oral biology) and Brenda Reader of Ohio State's IBMR; Jesusa Arevalo of UCLA; Gregory Miller and Edith Chen of Northwestern University; and Michael Kobor of the University of British Columbia.(http://www.eurekalert.org/pub_releases/2013-11/osu-eoc110513.php)




Oxidative stress  
is considered to be involved in 
a multitude of pathogenic processes  
and is also implicated in the process of aging.

Generation of reactive oxygen species (ROS) is inevitable for aerobic organisms and, in healthy cells, occurs at a controlled rate. Under conditions of oxidative stress, ROS production is dramatically increased, resulting in subsequent alteration of membrane lipids, proteins, and nucleic acids. Oxidative damage of these biomolecules is associated with aging as well as a variety of pathological events, including atherosclerosis, carcinogenesis, ischemia reperfusion injury, and neurodegenerative disorders.
oxidative stress detection
courtesy share: http://www.invitrogen.com

Tools to track different parameters in oxidative stress:  
(These tools use platforms such as fluorescence microscopy, flow cytometry, or microplate analysis.)
  • Generalized oxidative stress: Oxidative stress results from an imbalance in the production of reactive oxygen species (ROS) and the ability of the cell to scavenge them. ROS react with nucleic acids, proteins and lipids causing cell and tissue damage and can be measured using selective or general indicators.
Detection of oxidative stress
courtesy share: http://www.invitrogen.com

  • Lipid peroxidation: Lipid peroxidation is the oxidative degradation of lipids. Reactive oxygen species are the major initiators of lipid peroxidation and membrane bound polyunsaturated fatty acids like arachidonic acid and linoleic acid are their major targets. The byproducts of lipid peroxidation cause direct damage to cell membranes. They also form protein adducts resulting in cell and tissue damage. Lipid peroxidation is implicated in many human diseases including diabetes and cardiovascular disease.
Detection of lipid peroxidation
courtesy share: http://www.invitrogen.com

  • Selective ROS detection: Superoxide, peroxyl radical, hydrogen peroxide, hydroxyl radical and peroxynitrite are some examples of ROS that react with nucleic acids, proteins and lipids and result in cell and tissue damage. Certain ROS have been implicated in various human diseases including cancer, cardiovascular disease, neurodegenerative disease and aging.
Detection of superoxide in live cells

courtesy share: http://www.invitrogen.com

  • Glutathione levels: Reduced glutathione also known as GSH is a major thiol bound to proteins. Protein thiols including GSH play an important role in determining the redox status of cells. Therefore, detection of reduced GSH levels is a useful indication of redox potential and a cell's ability to prevent oxidative stress.
Detection of GSH in U2OS cells

courtesy share: http://www.invitrogen.com

#this report and picture therein is thankfully shared from:
http://www.invitrogen.com
http://zeenews.india.com/news/health/health-news/chronic-stress-effects-can-be-traced-to-your-genes_24897.html

Tuesday, November 5, 2013

Risk associated with hormone therapy for adenocarcinoma of prostate and newer approaches of treatment

Hormone therapy for prostate cancer causes kidney failure
Friday, July 26, 2013
(NaturalNews)

(http://www.naturalnews.com/041363_androgen_deprivation_therapy_prostate_cancer_kidney_failure.html)
Men who undergo conventional hormone therapy treatments for prostate cancer could be setting themselves up for another potential health problem later on in life: renal failure. This was the shocking finding of a recent study published in the Journal of the American Medical Association (JAMA), which found that androgen deprivation therapy (ADT), which suppresses testosterone, may lead to a rapid reduction in kidney function, and thus induce kidney failure.

Researchers from McGill University in Canada came to this conclusion after studying the effects of ADT in more than 10,000 men diagnosed with non-metastatic prostate cancer. Though the treatment can sometimes help induce prostate cancer regression in some men, it may also cause a hypogonadal condition that can eventually develop into acute kidney injury (AKI). In a worst-case scenario, ADT can lead to full renal failure, which can ultimately lead to death.

Novel class of drugs for prostate cancer
May 28, 2013
(http://www.sciencedaily.com/releases/2013/05/130528122514.htm)
In men with advanced prostate cancer, growth of cancer cells depends on androgen receptor signaling, which is driven by androgens, such as testosterone. To thwart tumor growth, most patients with advanced prostate cancer receive drugs that block the production of androgen or block the receptor where the androgen binds. Unfortunately, such treatments invariably fail and patients die of prostate cancer with their androgen receptor signaling still active and still promoting tumor growth.
In the new study, available online at Nature Communications, a team of researchers led by Dr. Ganesh Raj, associate professor of urology at UT Southwestern, found that they could disrupt androgen receptor signaling using a novel class of drugs called peptidomimetics. This therapeutic agent consists of an engineered small protein-like chain designed to mimic peptides that are critical for androgen receptor function. The peptidomimetic agents block the activity of the androgen receptor even in the presence of androgen by attacking the protein in a different spot from where the androgen binds.
Further testing is needed before a drug could move to Phase 1 clinical trials that involve human participants.
"Most drugs now available to treat advanced prostate cancer improve survival rates by three or four months," Dr. Raj said. "Our new agents may offer hope for men who fail with the current drugs."

New class of cancer treatment: Cell therapy
Lifespan boosting cancer vaccine developed in Russia
(http://www.itar-tass.com/en/c32/933583.html)
NOVOSIBIRSK, October 30 (Itar-Tass) - Scientists of the Institute of Clinical Immunology in the Siberian branch of the Russian Academy of Medical Sciences in Novosibirsk have developed a vaccine for the treatment of cancer, the institute's director, Professor Vladimir Kozlov, told Itar-Tass on Wednesday.
“We are deriving dendritic cells from the human body and loading them with tumor antigens," the scientist said. "Dendritic cells process them, then we inject the cells into the patient and they start working in the body evoking a strong immune response. That is, they are actively fighting the tumor."
The institute's creation "is not a classical vaccine, which is the means to prevent the illness", Professor Kozlov said. "In fact, it is cell therapy.”
The vaccine is counteracting several types of cancer - colorectal (bowel) cancer, breast cancer and prostate cancer - and the institute is ready to start its industrial production, Kozlov added.
He warned, however, that “one should not seek a panacea for malign tumors as they cannot be overcome with only one tool. Along with dendritic cells, there are other cells that fight cancer so all means are to be applied in complex. An immunomodulating cocktail is needed for a far-reaching effect,” Kozlov said.
Other types of therapy were to be used as well, such as chemotherapy and radiation therapy, the professor said. Treatment should vary case by case, he said, adding that the institute was already developing preventive vaccines against other illnesses, atherosclerosis among them, and that they would be presented soon.

Some related blog post reference:
6.benign prostatic hyperplasia could be adenocarcinoma prostate
7.androgen deprivation-hormone therapy for adenocarcinoma prostate