POLYMERASE AND ASTHMA
J Pharmacol Exp Ther. 2004 Dec;311(3):1241-8. Epub 2004 Jul 13.
Inhibition of poly(ADP-ribose) polymerase prevents allergen-induced asthma-like reaction in sensitized Guinea pigs.Suzuki Y, Masini E, Mazzocca C, Cuzzocrea S, Ciampa A, Suzuki H, Bani D.
Source
Department of Anatomy, Histology, and Forensic Medicine, Section of Histology, University of Florence, Viale G. Pieraccini, 6, I-50139 Florence, Italy.
Abstract
Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Because asthma is a chronic inflammatory disorder of the airways, we designed the present experimental study to evaluate the effects of PARP inhibition on allergen-induced asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, whereas they became severe in the sensitized animals. In the latter ones, ovalbumin aerosol also induced a rapid increase in PARP activity, bronchiolar constriction, pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis factor-alpha in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both PARP inhibitors were also able to prevent the above morphological and biochemical changes of lung tissue or bronchoalveolar lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the inactive analog of 3-aminobenzamide, had no effects.
PMID:
15254147
[PubMed - indexed for MEDLINE]
Free full text
http://www.jofamericanscience.org/journals/am-sci/am0706/99_5907am0706_593_599.pdfGene Knockout or Pharmacological Inhibition of Poly(ADP-Ribose) Polymerase-1 Prevents Lung Inflammation in a Murine Model of Asthma
1. A. Hamid Boulares,
2. Anna J. Zoltoski,
3. Zaki A. Sherif,
4. Puneet Jolly,
5. Donald Massaro and
6. Mark E. Smulson
+ Author Affiliations
1.
Department of Biochemistry and Molecular Biology and Department of Medicine, Lung Laboratory, Georgetown University School of Medicine, Washington, District of Columbia
1. Address correspondence to: Hamid Boulares, Ph.D., Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St., Room 5226, New Orleans, LA 70112. E-mail:
hboulr@lsuhsc.eduAbstract
Airway inflammation is a central feature of asthma and chronic obstructive pulmonary disease. Reactive oxygen species (ROS) contribute to inflammation by damaging DNA, which, in turn, results in the activation of poly(ADP-ribose) polymerase-1 (PARP-1) and depletion of its substrate, nicotinamide adenine dinucleotide. Here we show that prevention of PARP-1 activation protects against both ROS-induced airway epithelial cell injury in vitro and airway inflammation in vivo. H2O2 induced the generation of ROS, PARP-1 activation and concomitant nicotinamide adenine dinucleotide depletion, and release of lactate dehydrogenase in A549 human airway epithelial cells. These effects were blocked by the PARP-1 inhibitor 3-aminobenzamide (3-AB). Furthermore, 3-AB inhibited both activation of the proinflammatory transcription factor nuclear factor-κB and expression of the interleukin-8 gene induced by H2O2 in these cells. In a murine model of allergen-induced asthma, 3-AB prevented airway inflammation elicited by ovalbumin. Moreover, PARP-1 knockout mice were resistant to such ovalbumin-induced inflammation. These protective effects were associated with an inhibition of expression of the inducible nitric oxide synthase. These results implicate PARP-1 activation in airway inflammation, and suggest this enzyme as a potential target for the development of new therapeutic strategies in the treatment of asthma as well as other respiratory disorders such as chronic obstructive pulmonary disease.
http://meeting.chestpubs.org/cgi/content/abstract/128/4/147S-cAsthma Evaluation
Monday, October 31, 2005
2:30 PM - 4:00 PM
PREVALENCE OF MYCOPLASMA PNEUMONIAE INFECTION IN ASTHMATIC ADULTS IN INDIA
Nazima Nisar, PhD *, Randeep Guleria, MD, Arvind K. Singh, MD, Tirlok C. Chawla, PhD, Niranjan Nayak, MD and Nihar R. Biswas, MD
Department of Ocular Pharmacology, Dr. R.P.Centre for Ophthalmic Sciences, All I, New Delhi, India
PURPOSE: Mycoplasma pneumoniae ( M . pneumoniae ), primarily recognized as a causative agent of community acquired pneumonia has recently been linked to asthma pathogenesis. The lack of awareness and appropriate diagnostic facilities handicap the current understanding of their true prevalence in asthma . Polymerase chain reaction (PCR) is emerging as one of the most accurate methods for the rapid identification of M. pneumoniae in asthmatics. The purpose of present study is to see the prevalence of M. pneumoniae in asthmatics using PCR, culture and serology.
http://www.kenes.com/wspid2011/abstracts/pdf/331.pdfMYCOPLASMA PNEUMONIAE AND ASTHMA IN CHILDRENS. Kumar1, R.D. Roy1, G.R. Sethi2, S.R. Saigal1
1Department of Microbiology, 2Department of Pediatrics, Maulana Azad Medical College, New
Delhi, India
Background and aims: The etiology of asthma is complex, involving interactions between
genetic susceptibility, allergen exposure, and environmental factors, such as respiratory tract
infections, air pollution, and smoking. The role of Mycoplasma pneumoniae infection as a trigger
for asthma exacerbations is well documented. The aim of the present study was to investigate
role of M pneumoniae in childhood asthma using serology and polymerase chain reaction
(PCR).
Methods: Eighty children for this study were divided into two groups: Group 1 of 50 known
asthmatic children, aged 5-15 years with acute exacerbation and group 2 of 30 asthmatic
children controlled on inhaled corticosteroids. They were investigated for IgM and IgG
antibodies to M pneumoniae by enzyme linked immunosorbant assay and PCR assay to amplify
a 543 base pair P1 adhesion gene fragment applied on nasopharyngeal aspirates.
Results: Twenty one (42%) children in Group 1 and 4(13.3%) controls were positive for IgM
antibodies to M.pneumoniae (p= 0.0118). Ten (20%) children in Group I and 5(16%) in group 2
were positive for IgG antibodies to M.pneumoniae while three (6%) cases documented fourfold
rise in IgG titers. M pneumoniae PCR was positive in 3(6%) children of group 1 and none were
positive in group 2. No significant association of M pneumoniae with clinical features was found.
Conclusions: This study suggests that atypical agents like M pneumoniae may contribute to
asthma exacerbation. Also, treatment with macrolides may be of clinical benefit in patients with
asthma and evidence of M. pneumoniae infection.
http://www.rense.com/general3/genes.htmGenetic Vaccines & Mycoplasma
From Biowar <
biowar@topica.com>
From Rick <
rdharrison@compuage.com>
http://www.compuage.com/~rdharrison/Index.html9-17-00
The remarks toward the bottom about mycoplasma as a transport medium
for foreign DNA could equally apply to genetic vaccines as well as
offensive biowarfare agents.
http://www.sciam.com/1999/0799issue/0799weiner.htmlhttp://www.the-scientist.com/yr1998/mar/research_980316.html Excerpts from
The Ignorant & The Unwarned By Ed Gehrman
Nowadays, many diseases can be produced on an industrial scale using readily available resources. Trained technicians are easily able to culture large quantities of bacteria using methods formulated in U.S. bio-warfare labs; over a hundred Department of Defense funded laboratories are operating on campuses or in industrial parks across our nation. Our collective ignorance about participating in bio-warfare research is alarming and our seeming innocence, hypocritical. There are serious consequences in allowing our defense establishment and the scientific community to become involved in this grisly business. Some of the perilous drawbacks are shoddy scientific techniques, risky protocols, and the repressive secrecy that prevents peer review and free exchange of all information. (4)
There is a tendency in the scientific community to first ignore and then ridicule opinions that are contrary to prevailing beliefs; but a few balky doctors and health care workers have voiced their concern, often to a deaf public and media. Dr. Alan Cantwell M.D. represents this minority when he states: "Does the government secretly experiment with people? Of course, it does. This is not a paranoid fantasy. There is circumstantial evidence that shows AIDS is a man-made disease with a genetically engineered virus that came out of a cancer virus Bio-warfare laboratory. ...
Doctors Garth and Nancy Nicolson are prime examples of what can happen when one questions authority. They have been hounded from prestigious jobs and threatened, both physically and professionally; their labs have been vandalized, irreplaceable specimens destroyed, correspondence intercepted and phones tapped. Why? Because they had the audacity to suggest, and evidence to indicate that many sick gulf war vets are suffering from exposure to a bio-warfare, weaponized organism, a mycoplasma named incognitus.
Mycoplasma are the smallest and perhaps the oldest life forms. These cell wall deficient bacteria, one cause of "walking pneumonia", have been implicated in a variety of other "emerging" diseases. A form of mycoplasma, a spiroplasma, is implicated in Mad Cow Disease but is being ignored by most BSE researchers. Multiple Sclerosis, Chronic Fatigue Syndrome, and Alzheimers are also being investigated as possibly caused by mycoplasmic type bacteria. Mycoplasma are thought by many to be rather fragile, but nothing could be further from the truth. They tolerate extreme fluctuations in temperature, lay dormant in the soil for generations and survive the harshest elements; only drano-like chemicals kill them effectively outside the body. Under normal circumstances our immune system efficiently deals with mycoplasmas and other life-threatening bacteria; we evolved from this complicated, membrane enclosed piece of DNA and up until now have developed defenses that keep these critters in check. The new strains seem different. Difficult to spot in tissue, they do not react to normal bacterial tests. There has been no sure way to test for these organisms in living tissue since they are often not a problem until the immune system is exposed to stress. The symptoms are flu-like but to the extreme: headaches, sore joints, rashes, chest pain, heart problems, and neurological disorders. Dementia is common in advanced stages of these gruesome afflictions. (7)
The Nicolsons' test is able to identify the presence of mycoplasma in living tissue. The normal way to determine infection is to inject a lab animal with tissue or cultured material and wait for the lab animal to develop the target disease. The Nicolsons claim that a method they have invented named Gene Sequencing seems to do a much better and more accurate job. Labor intensive, thus expensive, Gene Sequencing has been peer reviewed and found to be credible and dependable. Government scientists and the Defense Department refuse to even consider the validity of this approach because if the Nicolsons are correct, and the mycoplasmic infections sickening the Gulf War vets are found to have originated in government funded bio-warfare labs, these programs will be exposed as the dangerous and shortsighted escapades they have become.
The USA supplies much of the know how and advanced technology used in this deadly endeavor. Microbiologists from every country study at our universities and learn all the necessary techniques needed to establish successful germ labs. Scientists from the USA were working with Iraq's microbiologists on bio-warfare just weeks before the Gulf War, and Iraq was importing highly toxic bacteria and viruses from companies in the USA. By 1990 they were manufacturing large quantities of botulism toxin and anthrax bacteria.
The Army command knew of the possibility that our forces could be exposed to toxic agents while stationed in Iraq; the compulsory inoculations, with multiple vaccines, indicates foreknowledge. But the Command didn't notify the troops about what was about to happen; they were participating in a huge experiment without their informed consent. They still have not been informed and most of the information surrounding the inoculations has been classified, the contents of the vaccines have still to be positively identified. One of the doctors who complained and refused to cooperate because she felt using force was a violation of the Geneva Protocols was court marshaled and given eighteen months in federal prison. (
"The nation's historical record on bio-warfare is replete with subterfuge, reckless experimentation, and rogue actions and is punctuated by violations of both domestic policy and international and national norms... the modern record is no more reassuring...If modern biology is to be a tool for human benefit, not the seed of our destruction, then all its facets, including military applications, must be opened to new levels of public understanding and to careful public scrutiny." (9)
...
These protocols may now be meaningless in an age of new technologies; advances in rDNA and cloning could produce a deadly new agent almost overnight, with relative ease. Recombinant DNA is a process known to most biologists and is easily accomplished in well equipped labs. Bacteria contain plasmids which are tiny pieces of DNA. This DNA is much smaller than, and independent of, the DNA contained in the chromosomes. The plasmids are removed from bacteria and then sliced apart using enzymes. A virus gene that has already been removed from the virus is fitted into the gap in the plasmid. Then this altered plasmid is inserted into a bacterium, where it can perform any number of tasks. As a bio-warfare bacterium the new DNA could manufacture toxins that would poison the body or cause disruptions in vital organs, like the brain. If mycoplasmas were the bacteria used in the transfer, they would be almost impossible to detect. Mycoplasmas have the ability to blend with the cell wall of the host and then move deeply into the nucleus of the cell where they stay hidden, waiting to emerge when the immune system weakens.
Mycoplasmas play only a small part in this tragic production. Any virus or bacteria that could cause a disease has or will be, or is now being studied and considered as a possible warfare agent. ...
End Notes
(1) Ivan L. Bennett, Jr., former Deputy Director of the U.S Office of Science and Technology before a symposium on chemical and biological warfare, sponsored by the National Academy of Sciences. Proc. N.A.S. 1970;65:250-279. Taken from Emerging Viruses:AIDS and Ebola.
(2) Lee Bowman, America Gets a Taste of Chemical Terror; April 26, 1997 Scripps Howard News Service. A well written news report; one of the few I've read that tries to point out the significant danger of bio-warfare.
(3) Dr. Frederick A. Murphy Talks about the Ebola Virus; An Interview by Sean Henahan, Access Excellence: a WWW site that supplies information about emerging diseases and viruses
(4)Dr. Garth Nicolson; From a discussion recorded by Gustav Grossman, 7-28-97
(5) This is from an interview I conducted, about a year ago, with Dr. Cantwell for my column in the Sonoma County Free Press. Dr. Cantwell has written two books on the genesis of the HIV: AIDS and the Doctors of Death & Queer Blood. Both are excellent. He has also written about the ability of bacteria to cause disease in the Cancer Microbe.
(6) This also is well documented information. Michael Gold's Conspiracy of Cells shows clearly the type of scientific errors that can occur on a regular basis, even in well run labs. Another look at scientific Snafus and downright skullduggery is the brilliantly researched Emerging Viruses:AIDS and Ebola, Nature, Accident or Genocide? by Leonard Horowitz. There is no need to distort or fabricate information concerning bio-warfare; the truth is there for all to see.
(7) I had previously researched the nature of mycoplasmas and spiroplasmas for an article I wrote on Transmissible Spongiform Encephlopathy : Mad Cows & Mad Scientists; FLATLAND #14. or Sonoma County Free Press. Mycoplasma type organisms are poorly understood, even by most scientists because they are so difficult to culture. They are often ignorantly discounted as the cause of disease. This could prove to be a fatal mistake for us all.
(8)From recorded conversations by Gustav Grossman 6-23-96. The Eight Myths of Operation Desert Storm & Gulf War Syndrome by Garth L. Nicolson, Ph.D., and Nancy L. Nicolson, Ph.D. The Institute for Molecular Medicine, P. O. Box 52470, Irvine, California 92619-2470 USA .
(9)From the introduction to Gene Wars:Military Control Over the New Genetic Technologies by Charles Piller and Dr. Keith Yamamoto. (10)Much of the above information can be found in Gene Wars . This is an important look at our government's bio-warfare program, the rationale and motives. It is also a plea to their fellow scientists to take a long, hard look at the pitfalls of continuing this dangerous activity. Written in 1986, it predicts clearly the type of problems that might arise, just as they did four years later during the Gulf War. Too bad we didn't listen.
