|
Noninvasive Detection of Macrophage-Rich Atherosclerotic Plaque in Hyperlipidemic Rabbits Using "Positive Contrast" Magnetic
Resonance Imaging
http://content.onlinejacc.org/cgi/content/short/52/6/483 Grigorios Korosoglou, MD*, ,*, Robert G. Weiss, MD, , Dorota A. Kedziorek, MD, Piotr Walczak, MD, Wesley D. Gilson, PhD, Michael Schär, PhD, , David E. Sosnovik, MD||, Dara L. Kraitchman, VMD, PhD, Raymond C. Boston, PhD¶, Jeff W.M. Bulte, PhD, Ralph Weissleder, MD, PhD|| and Matthias Stuber, PhD
* Department of Cardiology, University of Heidelberg, Heidelberg, Germany
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine,
Baltimore, Maryland
Department of Medicine, Cardiology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Philips Medical Systems, Cleveland, Ohio
|| Center for Molecular Imaging Research, Massachusetts General
Hospital, Harvard Medical School, Boston, Massachusetts
¶ School of Veterinary Medicine, University of Pennsylvania,
Kennett Square, Pennsylvania.
Manuscript received October 31, 2007; revised manuscript received February 12, 2008, accepted March 19, 2008.
* Reprint request and correspondence: Dr. Grigorios Korosoglou, University of Heidelberg,
Department of Cardiology, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. (Email: grigorios_korosoglou@med.uni-heidelberg.de
).
Objectives: This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively
by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance
imaging sequence (inversion recovery with ON-resonant water suppression [IRON]).
Background: The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive
thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique
that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis
would be of great potential clinical utility.
Methods: Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable
hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated
intravenously (2 doses of 250 µmol Fe/kg), and animals underwent serial IRON-MRI before injection of
the nanoparticles and serially after 1, 3, and 6 days.
Results: After administration of MION-47, a striking signal enhancement was found in areas of plaque only in
hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation
with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich
plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p <
0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in
control rabbits without atherosclerosis.
Conclusions: Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for
the noninvasive evaluation of macrophage-rich, vulnerable plaques.
Key Words: atherosclerosis  vulnerable plaque superparamagnetic nanoparticles molecular imaging inversion recovery with ON-resonant water suppression (IRON) positive contrast magnetic resonance imaging
| Abbreviations and Acronyms |
| CNR = contrast-to-noise ratio |
| FA = flip angle |
| IRON = inversion recovery with ON-resonant water suppression |
| MION = monocrystalline iron-oxide nanoparticle |
| MRA = magnetic resonance angiography |
| MRI = magnetic resonance imaging |
| NER = normalized enhancement ratio |
| ROI = regions of interest |
| SNR = signal-to-noise ratio |
| TE = echo time |
| TR = repetition time | |
Pharming
Shares Rise on Rhucin Study Results (Update1)
By Martijn van der Starre
July 11 (Bloomberg) -- Pharming NV, which uses the milk of genetically modified rabbits to make medicines, rose the most in two weeks in Amsterdam trading after
saying its most important new medicine, Rhucin, helped patients in a study.
Pharming gained 5 cents, 6.3 percent, to 85 cents, the biggest increase since June 25. That gives the company a market
value of 77.6 million euros ($123 million).
Tests found that Rhucin, a drug being developed to treat hereditary angioedema, a painful and sometimes fatal swelling
of tissue, was safe and effective in patients who were given as many as nine doses, the Leiden, Netherlands-based company
said today in a statement. Patients continued to respond to the medicine throughout treatment. Pharming seeks to accelerate
European and U.S. filings for the product.
``This data can increase the likelihood of approval of Rhucin,'' Huub Verschueren, an Amsterdam-based analyst at SNS Securities, wrote in a note to investors. ``However, we do not expect a decision'' by
European or U.S. regulators before the second quarter of 2009, said Verschueren, who has a ``sell'' rating on Pharming.
The results are from the treatment of 123 acute HAE attacks in 64 patients with different doses of the medicine, Pharming
said.
To contact the reporter on this story: Martijn van der Starre in Amsterdam at vanderstarre@bloomberg.net
Long QT syndrome boosts risk of sudden death due to irregular heartbeats
From ANI
Washington,
May 11: A new study from Brown University, Providence has revealed that individuals with long QT syndrome (LQTS) are at an
increased risk of sudden death due to irregular heartbeats, also known as a cardiac arrhythmias. Lead researcher Gideon Koren
generated two rabbit models of LQTS for the study provides new insight into the mechanisms by which
these mutations might produce an irregular heartbeat in humans.
Mutations in several genes including KCNQ1 and KCNH2
have been shown to cause the disease.
For the study, the researchers used rabbits expressing either KCNQ1 or KCNH2
mutants that generate proteins with the same functional defect as found in individuals with LQTS.
The findings revealed
that the heart defects observed in the rabbits mirrored those observed in individuals with LQTS and more than 50pct of the
rabbits carrying the KCNH2 mutant died suddenly due to irregular heartbeats in their first year of life.
The proteins
generated by the KCNQ1 and KCNH2 mutants prevented proteins generated by the corresponding non-mutant form of the gene from
working and, importantly, no compensation for the loss of function of either protein was observed.
As compensation
for the loss of function of the proteins generated by the KCNQ1 and KCNH2 mutants is observed in mouse models of LQTS these
data provide important insight into the mechanisms underlying the disease.
Isovolaemic haemodilution decreases the shivering threshold in rabbitshttp://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1861516
Y. Imaia1, M. Yamakagea2 c1, H. Satoa1, K. Okuyamaa1, T.
Ishiyamaa1 and T. Matsukawaa1
a1 University of Yamanashi, Faculty of Medicine, Department of Anesthesiology, Chuo, Yamanashi,
Hokkaido, Japan
a2 Sapporo Medical University School of Medicine, Department of Anesthesiology, Sapporo, Hokkaido,
Japan | |
|
Summary
Background and objective The inhibition of thermoregulatory control by anaesthesia
is manifested by reduced vasoconstriction and shivering thresholds. As intraoperative bleeding can result in haemodynamic
changes, including vasoconstriction, we investigated the effect of experimental bleeding on the shivering threshold in rabbits.
Methods Twenty-four rabbits were randomly assigned to one of three treatment
strategies: (1) no blood removal (control), (2) 5 mL kg−1 isovolaemic blood removal and (3) 10 mL kg−1
isovolaemic blood removal. After tracheal intubation under isoflurane anaesthesia, anaesthesia was maintained with 50% nitrous
oxide in oxygen. The removed blood volume was replaced with the same volume of warm hydroxyethyl starch colloid solution.
Oesophageal temperature was measured as a core temperature at 1-min intervals. After blood removal, the animal’s body
was cooled at a rate of 2–3°C h−1 by perfusing water at 10°C through a U-shaped thermode positioned
in the colon. Hypothermic shivering was evaluated by visual inspection, and the core temperature at which shivering was triggered
was identified as the thermoregulatory threshold for this response.
Results Just before the cooling, the body temperature of the animals was around
38.6°C in all of the three groups. The shivering threshold in the control group was 37.2 ± 0.2°C (mean ± SD). The shivering
thresholds in the 5 mL kg−1 (36.9° ± 0.3°C) and 10 mL kg−1 (36.5° ± 0.5°C) blood removal
groups were significantly lower and in proportion with the volume of blood removed than that in the control group.
Conclusion Isovolaemic haemodilution decreased the shivering threshold in
rabbits in proportion with the volume of blood removed.
(Accepted January 19 2008)
Key Words: SHIVERING; HAEMODILUTION; RABBIT; ANAESTHESIA INHALATIONAL
Correspondence:
c1 Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido
060-8543, Japan. E-mail: yamakage@sapmed.ac.jp; Tel: +81 11 611 2111 Ext. 3568; Fax: +81 11 631 9683
|
News |
 |
|
Infusions of apoA-1 mimetic peptide regress
aortic-valve stenosis in animal model
Compared with controls, infusions of the
apoA-1 mimetic peptide induced a greater improvement of the aortic-valve area and a significant reduction in aortic-valve
thickness, report investigators. (Busseuil D et al. Br J Pharmacol 2008; published online before print April 14, 2008.)
Low back pain is common among smokers, says study
| Published: Wednesday, 30 April, 2008, 01:42 AM Doha Time | |
|
Staff Reporter
DEGENERATION of intervertebral discs,
which results in low back pain, is more common among smokers and correlated with the duration of exposure to nicotine, an
experimental study by researchers at Qatar University has revealed.
A presentation on the study was made at the first annual
Qatar University Research Forum (QURF) yesterday by Nahla M Afifi (Health Sciences Department, College of Arts & Sciences).
The
background for the research was the clinical observation that a large proportion of patients presenting with low back pain
are smokers.
Intervertebral discs are the pillow-like cushions in the vertebrae. They are the spine’s shock-absorbing
system, helping easy movement.
“We investigated the histological effects of nicotine on the lumbar intervertebral
discs of a group of rabbits,” explained Afifi, who conducted the study in association with
Kawther A Hafez (Department of Anatomy, Faculty of Medicine, Ain Shams University).
In all, 18 rabbits, divided into three
equal groups, were used in the experiment. While Group one was left untreated, the rabbits in groups two and three were injected
with 5000ng/kg nicotine into the peritoneum, the serous membrane that forms the lining of the abdominal cavity, daily for
four weeks and eight weeks, respectively.
“The selected dose produced blood nicotine levels equivalent to those found
in heavy smokers who would use about 30 cigarettes a day,” the researcher said.
Light and electron microscope studies
revealed that nicotine injection showed a variety of histological changes in the intervertebral discs of rabbits in groups
two and three.
http://www.gulf-times.com/site/topics/article.asp?cu_no=2&item_no=215762&version=1&template_id=36&parent_id=16 |
Tissue engineers grow penis in the lab
| |
In a remarkable feat of tissue engineering, major parts of the penises of several rabbits
have been replaced with segments grown in a lab from their own cells. The animals were able to use the reconstructed organs
to mate.Tissue engineers who recently demonstrated penis replacement in animals have now added a vital missing component -
nerve cells. "The nerve cells are very important - they are responsible for all the sensory function," says Anthony Atala,
at Boston Children's Hospital. "In order to do complete [penile] replacements we need to make sure all of the parts are there,
including the nerves."
| |
|
[Chicago - États-Unis] - 28-04-2008 (American Urological Association in Chicago) | http://www.icicemac.com/news/index.php?nid=10071&pid=65
PETA boycotting Mars candy co. over animal cruelty
http://www.reuters.com/article/domesticNews/idUSN0731748320071208
Web site about the story
http://www.marscandykills.com
WASHINGTON (Reuters) - People for the Ethical Treatment of Animals (PETA) is calling for a boycott of M&Ms, Twix
candy bars and other snack foods made by Mars Inc, claiming the company funds experiments that kill mice, rats, guinea pigs
and rabbits.
"In violation of its own written policy, the candy company is currently
funding a study at the University
of California, San Francisco,
that uses rats. The rats are force fed by having plastic tubes shoved down their throats, and they are then cut open and killed,"
PETA said in a statement.
"In response to this new information,
PETA is filing a legal complaint with the Federal Trade Commission (FTC) over Mars' false statement," the group said in a
statement. The FTC investigates claims of dishonesty in advertising.
Mars spokeswoman Alice Nathanson said regarding the University of California experiment: "I can't
speak to any information that PETA may or may not have. I can't speak to any experiments."
But, she said that the privately held company "would never issue or post
a statement that we were not 100 percent confident in."
PETA spokeswoman Kathy Guillermo said in an interview the experiments seemed
aimed at developing health claims for chocolate because it contains flavonoids.
Health studies have found that flavonoids protect against heart disease
and cancer.
Guillermo said the boycott would start on Monday.
Mars says on its Web site that it bars animal research "involving euthanasia,
vivisection or the suffering of any animal" in developing its snacks, drinks and pet products.
But the Web site also says that a separate business unit, Symbioscience, would undertake "limited forms
of animal testing" when required to demonstrate the safety or efficacy of "pharmaceutical and therapeutic food products."
PETA said in its statement that Mars paid for experiments in which mice
had to swim in a pool of water and paint and find a hidden platform to avoid drowning and were killed later.
The group also accused Mars of funding an experiment in which plastic tubes
were surgically attached to guinea pigs' carotid arteries and cocoa ingredients were injected into their jugular veins to
cause a sharp drop in blood pressure, and another experiment in which rabbits
were fed high-cholesterol diets with varying amounts of cocoa and later the main blood vessels to their hearts were cut out
and examined.
The University of California, San Francisco, declined
immediate comment.
From The Sunday
Times
December 30, 2007
Health food fads spark huge rise in animal testing
Marie Woolf, Whitehall Editor
THE trend for healthier eating has led to an increase of more than 300% in the number of laboratory experiments conducted
on animals for food additives, sweeteners and health supplements over the past year.
Home Office figures showed an
increase from 862 to 4,038 experiments from 2005 to 2006.
The disclosure will ignite an ethical debate about the way
animals have become victims of the fad for health foods. Animal welfare groups said many of the tests are unnecessary or could
be performed on humans.
The experiments often involve using painful procedures and artificially induced injuries to
research the effects of food.
In a test at Glasgow University, rodents were fed raspberry juice and then killed to
see where the juice had gone in their kidneys, liver and brains. At Hammersmith hospital, west London, rats were force-fed
fish supplements, while at Glasgow Caledonian University they had the food supplement ginkgo biloba injected into their paws.
At
Robert Gordon University, Aberdeen, rats were fed a diet containing 20% raw, lightly cooked or fully cooked cabbage for two
weeks. The animals were killed to examine the effects of the diet on their liver and colon. The researchers had already carried
out a human study on the effects on the gut of eating cooked cabbage.
Other experiments included feeding a health drink
to rats to see whether they ate more chocolate, vanilla or asparagus flavour.
Although most food tests are performed
on rodents, rabbits, guinea pigs and dogs are also used.
In experiments in the United States, Teavigo, a purified green tea extract, available by mail order in Britain, was rubbed
onto the shaved backs of guinea pigs and rabbits and put in the eyes of live rabbits.
Dogs force-fed huge doses of Teavigo - which is marketed as “green tea in its purest form” and a choice for
“health-conscious consumers” - died or had to be put down.
Gerhard Gans, director of regulatory affairs at DSM Nutritional Products, which produces Teavigo, said: “In some
cases it is necessary to use dogs, they are in some aspects more similar to humans than rats . . . where it is possible to
use alternative methods validated by the authorities we will use [them].”
Home Office statistics show that in addition to the experiments for additives there was a 30% increase to 7,477 tests on
animals for other foods from 2005-6.
A spokesman said the tests on food are needed to meet regulatory requirements.
Michelle Thew, chief executive of the British Union for the Abolition of Vivisection, said: “The rise in testing
of food on animals in the race to find the next lucrative ‘super-food’ is a hidden scandal. People are unaware
of the animal suffering behind the headlines.”
doi:10.1016/j.anbehav.2006.09.031  Copyright © 2007 The Association for the Study of Animal Behaviour Published by Elsevier
Ltd.
Animal economics: assessing the motivation of female laboratory rabbits to reach a platform, social contact and food
Shirley C. Seaman*,  ,  , Natalie K. Waran†, 1, Georgia Mason‡, 2 and Richard B. D'Eath§, 3 †School of Natural Sciences, Unitec New Zealand, New Zealand ‡Department of Animal & Poultry Science, University of Guelph, Canada *Royal (Dick) School of Veterinary Studies, University of Edinburgh, U.K. §Animal Behaviour & Welfare, Sustainable Livestock Systems, Scottish Agricultural College (SAC) Edinburgh,
U.K. Received 23 February 2006; revised 13 April 2006; accepted 5 November 2006. MS. number: 8859.
Available online 19 December 2007.
We used novel techniques for assessing resource value to investigate what additions to a barren cage female laboratory
rabbits, Oryctolagus cuniculus, value. We tested motivation to reach two resources that are potentially practical enrichments:
a platform (providing a partly enclosed space and a raised area) and limited social contact with another rabbit through wire
mesh and compared these to food and an empty space. To reach these resources, rabbits had to pay entry costs (pushing through
weighted doors) which increased every 2 days. With rising costs, rabbits generally rescheduled their behaviour, often reducing
visit number and increasing visit length. Measures from economics and behavioural ecology ranked the relative importance of
resources similarly (food ≥ social contact ≥ platform > empty cage). ‘Travel
cost consumer surplus’ (the area under a demand curve of price versus number of visits) ranked food and social contact
similarly, but higher than the platform; ‘aggregate consumer surplus’ (the area under a plot of weight against
the number of rabbits paying each price level for the resource) placed food higher than both social contact and the platform;
‘reservation price’ (maximum weight pushed) did not discriminate between the three resources; and ‘expenditure
rate’ (weight × visits/days) again ranked food and social contact similarly, but higher than the platform.
Overall, rabbits' motivation for access to limited social contact thus came close to that for food, suggesting that they value
this highly. Rabbits were almost as strongly motivated to be near a platform, but rarely used it, suggesting it might serve
a ‘bolt hole’ function.
Keywords: access costs; animal economics; consumer demand; laboratory rabbit; motivation; Oryctolagus
cuniculus; resource value
Correspondence: S. C. Seaman, Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh,
Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, U.K.
1 N. K. Waran is at the School of Natural Sciences, Unitec New Zealand, Private Bag 92025, Carrington Road, Mt Albert,
Auckland, New Zealand.
2 G. Mason is at the Department of Animal & Poultry Science, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
3 R. B. D'Eath is at SAC, Kings Buildings, West Mains Road, Edinburgh EH9 3JG, U.K.
Oral and maxillofacial surgery
Radiographic and histomorphometric analysis of bone healing using autogenous graft associated with platelet-rich plasma
obtained by 2 different methods
Marcia Hatakeyama Mastera, , , Marcelo E. Beletti PhDb, Darceny Zanetta-Barbosa PhDc and Paula Dechichi PhDd aMaster, Oral & Maxillofacial Surgery and Implantology Department, Federal University of Uberlândia-UFU, Brazil. bSão Paulo University-USP, Brazil; Adjunct Professor, Morphology Department, Federal University of Uberlândia-UFU,
Brazil. cSão Paulo State University-UNESP, Brazil; Center for Oral Health Science, Lund University, Sweden; and Titular
Professor, Oral & Maxillofacial Surgery and Implantology Department, Federal University of Uberlândia-UFU, Brazil. dSão Paulo University-USP, Brazil; Adjunct Professor, Morphology Department, Federal University of Uberlândia-UFU,
Brazil. Received 11 February 2007; revised 28 June 2007; accepted 23 July 2007. Available online 22
December 2007.
The aim of this study was to conduct radiographic and histomorphometric analysis of bone healing in the calvaria of rabbits,
using an autogenous graft associated with PRP obtained by 2 different methods. Thirty rabbits were divided into control and
experimental groups. Lesions were produced in the calvaria and filled with autogenous graft (control) or autogenous graft
and PRP obtained by the Anitua or modified Sonnleitner methods. The animals were humanely killed 15 days after surgery and
the calvarias were radiographed. The radiographs were digitized to assess the radiographic density. By histologic images of
the lesion, the bone matrix was quantified. There were no significant differences in the radiographic density and the bone
matrix area between the groups. The association of PRP with autogenous bone did not improve the healing process, irrespective
of the method used early during healing.
doi:10.1016/j.otohns.2007.10.024 Copyright © 2008 American Academy of Otolaryngology–Head and Neck Surgery Foundation
Published by Mosby, Inc.
Original research—laryngology and neurolaryngology
Experimentally induced phonation increases matrix metalloproteinase-1 gene expression in normal rabbit vocal fold
Paper presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Washington, D.C.,
Sept. 16-19, 2007.
Bernard Rousseau PhDa, , , PingJiang Ge MDb, Lesley C. French MDa, David L. Zealear PhDa, Susan L. Thibeault PhDc and Robert H. Ossoff DMD, MDa
aDepartment of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication
Sciences
bDepartment of Otolaryngology, GuangDong Province People’s Hospital
cDepartment of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin-Madison.
Received
30 August 2007; revised 24 October 2007; accepted 25 October 2007. Available online 27 December 2007.
Objectives
An in vivo rabbit model was used to study the effect of 3 hours of experimentally induced phonation on messenger RNA expression
of the normal vocal fold.
Study Design
Prospective; animal model.
Subjects and Methods
Ten rabbits received experimental phonation for 3 hours, followed by 1 hour of recovery. A separate group of 5 rabbits
served as no-phonation controls. We measured messenger RNA expression of matrix metalloproteinase-1, MMP-9, and interleukin-1β
using real-time reverse-transcribed polymerase chain reaction. Gene expression ratios from phonation and control animals were
assessed with the Mann-Whitney U test.
Results
Phonation (77 ± 3 dB; 429 ± 141 Hz) resulted in increased matrix metalloproteinase-1 gene expression from rabbits receiving
experimental phonation compared with controls, and a nonsignificant increase in matrix metalloproteinase-9 and interleukin-1β
gene expression.
Conclusion
Matrix metalloproteinases play a role in maintaining tissue homeostasis. Investigation of cellular responses to experimental
phonation may provide insight into how matrix metalloproteinases and other extracellular matrices contribute to maintenance
of the vocal fold and development of pathology.
Corresponding author: Bernard Rousseau, PhD, Vanderbilt University, Department of Otolaryngology, 1313 21st
Avenue South, Room 602, Nashville, TN 37232-4480.
| Docs jump with joy at cloned bunny |
| By Rachel Yan 2007-12-15 |
LOCAL researchers have produced the world's first gene-modified cloned rabbit.
The rabbit is to be used in research
to find out causes of human diseases, Jiao Tong University officials said yesterday.
The rabbit was born on September
14 in the city's Xinhua Hospital affiliated to Jiao Tong's medical school and weighs 1,400 grams.
Although it appears
to be an ordinary rabbit, the gene-modified clone creature is different from its peers as it exudes green lights when it is
put under the examination of a fluoroscope.
"That's because we have injected special genes into the rabbit," said Chen
Xuejin, vice professor with Jiao Tong's medical school and the research team leader.
"That is the other cutting-edge
technology that is used in this experiment aside from the clone methodology."
Chen and his colleagues started the test
by extracting glowing protein genes from a jellyfish. With physical and chemical treatment, the gene was transplanted into
the rabbit's fiber cells before the gene-modified cell was injected into a rabbit embryo.
The next step was to place
the reconstructed embryo into the body of a female rabbit. It was born by caesarean section after a pregnancy period of 30
days.
The team produced other rabbits using the same cloning technology with gene modification but most of them died
soon after birth.
To avoid premature death, researchers found a nanny rabbit which had just given birth and put it
with newborn peers.
As rabbits share similar genes with human beings, the gene-modified clone rabbit is expected to
be used in disease research.
It would be of special help in the study of eye diseases and cardiovascular conditions,
said Li Shangang, a researcher with the Chinese Academy of Agricultural Sciences.
How To Design A Cancer-killing Virus
http://www.sciencedaily.com/releases/2007/10/071025174714.htm
ScienceDaily (Oct. 29, 2007) — One new way to treat individuals with cancer that is being
developed is the use of viruses that infect and kill cancer cells while leaving normal cells unharmed. These viruses are known
as virotherapeutics.
In a new study, David Kirn and colleagues at Jennerex Biotherapeutics, San Francisco, have described the development of
a new virotherapuetic with antitumor effects in both mice and rabbits.
After selecting a highly potent strain of poxvirus that was able to traffic to tumors when administered intravenously to
mice the authors engineered the virus such that it would target only specific cancer cells -- those with increased expression
of a protein known as E2F and/or activation of signaling downstream of a protein known as EGFR.
Further engineering to enable the virus to produce the soluble factor GM-CSF was designed to enhance the induction of anti-tumor
immune responses. In addition to its antitumor effects in mice and rabbits, the virotherapeutic showed high selectivity for
cancer cells in tumor-bearing rabbits and in human tissue samples, leading the authors to suggest that this virotherapeutic
should be tested in clinical trials for the treatment of cancer.
Article: Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus,
JX-963, Journal of Clinical Investigation, October 25, 2007.
Adapted from materials provided by Journal of Clinical Investigation.
Radio waves destroy nanotubes-embedded cancer tumours in rabbits
http://www.topnews.in/radio-waves-destroy-nanotubes-embedded-cancer-tumours-rabbits-24953
Washington, November 2 : Radio waves have been found to offer a non-invasive method to destroy cancer cells treated with
carbon nanotubes in pre-clinical experiments led by scientists at the University of Texas M. D. Anderson Cancer Center and
Rice University.
Writing about their findings in the journal Cancer, the researchers said that radio waves that heat up the nanotubes while
sparing untreated tissue enabled them to destroy liver cancer tumours in rabbits completely.
The technique did not produce any side effects, though some healthy liver tissue within two to five millimetres of the
tumours sustained heat damage due to nanotube leakage from the tumour.
"These are promising, even exciting, pre-clinical results in this liver cancer model. Our next step is to look at ways
to more precisely target the nanotubes so they attach to, and are taken up by, cancer cells while avoiding normal tissue,"
says senior study author Dr. Steven Curley, professor in M. D. Anderson's Department of Surgical Oncology.
He believes that targeting the nanotubes solely to cancer cells is the major challenge in advancing the therapy, and reckons
that a clinical trial is at least three to four years away.
During the study, a solution of single-walled carbon nanotubes was injected directly into the tumours. The researchers
then exposed the four treated rabbits to two minutes of radiofrequency treatment, resulting in thermal destruction of their
tumours.
Control group tumours that were treated only by radiofrequency exposure or only by nanotubes remained undamaged.
In laboratory experiments, two lines of liver cancer cells and one pancreatic cancer cell line were destroyed after being
incubated with nanotubes and exposed to the radiofrequency field.
"I'm humbled by the results of this research. I realize it's early in the race, but Dr. Curley and his team have moved
on this carefully with utmost speed. I look forward to continuing to work with them and hopefully to watching the first person
be treated with this procedure. The race isn't over but it needs to be taken to the finish line," says entrepreneur John Kanzius
of ThermMed LLC, who invented the experimental radiofrequency generator used in the experiments.
Dr. Curley says that radiofrequency energy fields penetrate deeply into tissue, and thus it may be possible to deliver
heat anywhere in the body if targeted nanotubes or other nanoparticles can be delivered to cancerous cells.
Without such a target, radio waves will pass harmlessly through the body, he adds. (ANI)
BUAV short statement on new EU animal
experiment statistics
http://www.politics.co.uk/press-releases/opinion-former-index/animal-welfare/buav-short-statement-on-new-eu-animal-experiment-statistics-$481209.htm
Thursday, 08 Nov 2007 14:27
BUAV Chief Executive Michelle Thew said: Despite European Commission
and member state’s individual promises to reduce and replace the use of animals in experiments, the total animals used
in experiments in 2005 rose to 12.1 million – representing a 3.2 per cent increase over and above the added numbers
from the inclusion of 10 new member states in the 2005 report. We are shocked and appalled to hear that the number
of animals condemned to lives of suffering in EU laboratories has hit a ten year high. It is simply morally indefensible that
in the 21st century some of the most advanced laboratories in the world are still pouring tens of millions of public money
into the type of research that belongs in the dark ages. For example, there was a 107 per cent increase in cosmetic research
on animals. We now as a society must insist that our politicians listen to the overwhelming voice of European citizens and
act now to end the suffering. They have a unique opportunity under the current revision of the directive that governs animal
testing to close the door on outdated practice, and move the EU forward into an era of modern, humane research. Key
Facts arising from the report:
The UK is the second largest user of animals in the EU after France. Germany is the third biggest user. The use of animals
by these top three countries represents 50 per cent of all animal use in experiments in the EU. Germany’s use, however,
decreased by 12 per cent in 2005, while the use of animals by France and the UK both rose (5 per cent and 3 per cent respectively).
The largest proportion of experiments using animals (33 per cent) were fundamental biological research – which are
designed just to see what happens too an animal if you subject it to certain conditions. For example, researchers at various
universities in the UK are legally allowed to implant electrodes into the brains of macaques for the purposes of understanding
how their brain responds to things that they see. After the surgery, monkeys are restrained by their heads in chairs and made
to watch tv screens whilst the researchers make recordings from the electrodes in their brains. There is no direct medical
benefit to this research (J Neurosci Methods 2006)
Over 24,000 dogs and 10,000 primates were used in experiments – the use of so-called ‘new world’ monkeys
such as marmosets leapt by 31 per cent, despite overwhelming public and increasing scientific opposition to their use.
The use of rabbits, ferrets and birds increased by hundreds of thousands.
There was a 107 per cent rise in the use of animals for cosmetics testing. 5,571 animals, including 900 guinea pigs and
600 rabbits were used despite regulatory approval and widespread availability of alternatives.
231,613 animals were poisoned to death in studies like the LD50 – including 841 dogs. The LD50 is a toxicity test
where researchers test the amount of a substance it takes to kill fifty per cent of the animals.
Ends
NOTES
TO EDITOR
The European Commission releases statistics on animal experimentation by member states every three years.
They released the figures for 2005 today (November 8th 2007). Click here to see the full report
*Directive 86/609 that governs the use of animals in experiments is currently being reviewed by the European Commission.
The BUAV has been campaigning for over 100 years to achieve a world where nobody wants or believes we need to experiment
on animals. We are committed to achieving our aims through reliable and reasoned evidence-based debate. We are proudly non-violent
and respect the quality of life for all – animals and people.
For more information contact: Media Manager Mary-Louise
Clews 020 7619 6978/Out of hours mobile: 07850 510 955 /mary-louise.clews@buav.org
Anthony D. Cristilloa, Deborah Weissa, Lauren Hudacika, Susana Restrepoa, Lindsey Galmina, John Suschaka, Ruxandra Draghia-Aklib, Phillip Markhama and Ranajit Pala, , aAdvanced BioScience Laboratories, Inc., Department of Cell Biology, 5510 Nicholson Lane, Kensington, MD 20895,
USA bVGX, Pharmaceuticals, Immune Therapeutics Division, USA Received 8 November 2007. Available online 26
November 2007.
Abstract
Intramuscular needle injection of HIV-1 DNA vaccines typically elicits weak immune responses in immunized individuals.
To improve such responses, the immunogenicity of a vaccine consisting of electroporated DNA followed by intramuscular protein
boost was evaluated in rabbits and macaques. In macaques, electroporation of low dose DNA encoding HIV-1 env followed
by gp120 protein elicited Th1 cytokines and functional CTL that persisted for over 1 year. In both macaques and rabbits, robust
anti-envelope antibodies, elicited by electroporated DNA, were augmented by gp120 protein and such responses neutralized sensitive
SHIV isolates. These findings highlight efficient priming of immune responses by electroporated DNA that in conjunction with
protein boost may give rise to long-term immunity in immunized hosts.
Keywords: HIV-1; Vaccine; Electroporation; Cellular immunity; Humoral immunity; DNA vaccines
Corresponding author. Fax: +1 301 468 9466.
| Note to users: The section "Articles in Press" contains peer reviewed accepted articles to be published in this journal.
When the final article is assigned to an issue of the journal, the "Article in Press" version will be removed from this section
and will appear in the associated published journal issue. The date it was first made available online will be carried over.
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the journal's reference style for the exact appearance of these elements, abbreviation of journal names and the use of punctuation.
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the Editorial Board. The articles have not yet been copy edited and/or formatted in the journal house style.
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will be corrected by the authors. Therefore the text could change before final publication.
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|
Immunosuppression transitoire induite chez le lapin et la souris par le spumarétrovirus humain prototype HFV (virus spumeux
humain)
M. Santillana-Hayata, F. Rozaina, P. Bittouna, C. Chopin-Roberta, J. Lasnereta, J. Périès, a and M. Caniveta aUPR A0043 CNRS, Rétrovirus et Rétrotransposons des Vertébrés, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux,
75475 Paris Cedex 10, France Received 30 November 1992; accepted 30 August 1993. Available online 30 November
2007.
Summary
Spumaviruses (foamy viruses) constitute one of the three retroviral genera isolated from man. Although spumaviruses have
not been clearly linked to a given pathology in humans and other infected species, it is well established that they lead in
vivo to chronic infections without detectable viral expression. We thought it of interest to investigate certain aspects
of the pathology induced in laboratory animals by human foamy virus (HFV). In this work, we demonstrate that HFV infection
of rabbits and mice gives rise to a transient immunosuppressive effect, as evaluated in vitro by lymphocyte transformation
tests. This phenomenon occurs shortly after viral inoculation, at around 4–5 days, and regresses within thirty days.
Les spumarétrovirus («foamy viruses) constituent un des trois genres rétroviraux isolés chez l'homme. Ils ne donnent lieu
à aucune pathologie connue, ni chez l'homme ni chez les autres espèces naturellement infectées, mais ils déterminent des infections
chroniques sans expression virale apparente. Dans ce contexte, nous avons examiné certains aspects de la pathologie expérimentale
induite chez des animaux de laboratoire par le prototype spumarétroviral humain: HFV. Nous démontrons que ce virus est capable
de donner lieu chez le lapin et la souris à une immunosuppression cellulaire passagère que nous avons évaluée par des essais
de transformation lymphocytaire in vitro. Cette immunosuppression apparaît environ 4–5 jours après l'inoculation
et disparaît dans un délai de 30 jours.
Author Keywords: Foamy virus, HFV, Retrovirus, Lectin, Lymphocyte, Splenocyte, Immunosuppression; Rabbit,
Mouse
Mots-clés: Virus spumeux, HFV, Rétrovirus, Lectine, Lymphocyte, Splénocyte, Immunosuppression; Lapin,
Souris
Corresponding author.
UPDATE: FDA Approves ISENTRESS(TM) (raltegravir)
Tablets, .
(10º) First-in-Class Oral HIV-1 Integrase Inhibitor
|
First-in-Class Oral HIV-1 Integrase Inhibitor 12/10/2007 23:34:00 Business Wire Coadministration
of ISENTRESS with other drugs that inhibit UGT1A1 may increase plasma levels of raltegravir.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy Pregnancy Category C ISENTRESS should be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus.
There are no adequate and well-controlled studies in pregnant women.
In addition, there have been
no pharmacokinetic studies conducted in pregnant patients.
Developmental toxicity studies were performed in rabbits (at
oral doses up to 1000 mg/kg/day) and rats (at oral doses up to 600 mg/kg/day).
The reproductive toxicity study in rats
was performed with pre-, peri-, and postnatal evaluation.
The highest doses in these studies produced systemic exposures
in these species approximately 3- to 4-fold the exposure at the recommended human dose.
In both rabbits and rats, no treatment-related
effects on embryonic/fetal survival or fetal weights were observed.
In addition, no treatment-related external, visceral,
or skeletal changes were observed in rabbits.
However, treatment-related increases over controls in the incidence of supernumerary
ribs were seen in rats at 600 mg/kg/day (exposures 3-fold the exposure at the recommended human dose).
Placenta transfer
of drug was demonstrated in both rats and rabbits.
At a maternal dose of 600 mg/kg/day in rats, mean drug concentrations
in fetal plasma were approximately 1.5- to 2.5-fold greater than in maternal plasma at 1 hour and 24 hours postdose, respectively.
Mean
drug concentrations in fetal plasma were approximately 2% of the mean maternal concentration at both 1 and 24 hours postdose
at a maternal dose of 1000 mg/kg/day in rabbits.
Antiretroviral Pregnancy Registry To monitor maternal-fetal outcomes of
pregnant patients exposed to ISENTRESS, an Antiretroviral Pregnancy Registry has been established.
Physicians are encouraged
to register patients by calling 1-800-258-4263.
8.3 Nursing Mothers Breast-feeding is not recommended while taking ISENTRESS.
In
addition, it is recommended that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission
of HIV.
It is not known whether raltegravir is secreted in human milk.
However, raltegravir is secreted in the milk
of lactating rats.
Mean drug concentrations in milk were approximately 3-fold greater than those in maternal plasma at
a maternal dose of 600 mg/kg/day in rats.
There were no effects in rat offspring attributable to exposure of ISENTRESS
through the milk.
8.4 Pediatric Use Safety and effectiveness of ISENTRESS in pediatric patients less than 16 years of age
have not been established.
8.5 Geriatric Use Clinical studies of ISENTRESS did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience
has not identified differences in responses between the elderly and younger subjects.
In general, dose selection for an
elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and
of concomitant disease or other drug therapy.
8.6 Use in Patients with Hepatic Impairment No clinically important pharmacokinetic
differences between subjects with moderate hepatic impairment and healthy subjects were observed.
No dosage adjustment
is necessary for patients with mild to moderate hepatic impairment.
The effect of severe hepatic impairment on the pharmacokinetics
of raltegravir has not been studied (see Clinical Pharmacology (12.3)).
8.7 Use in Patients with Renal Impairment No clinically
important pharmacokinetic differences between subjects with severe renal impairment and healthy subjects were observed.
No
dosage adjustment is necessary (see Clinical Pharmacology (12.3)).
10 OVERDOSAGE No specific information is available on
the treatment of overdosage with ISENTRESS.
Doses as high as 1600-mg single dose and 800-mg twice-daily multiple doses
were studied in healthy volunteers without evidence of toxicity.
Occasional doses of up to 1800 mg per
http://www.infobolsa.es/v2002/Noticias/noticias_titulares2.asp?Fuente=IBNW&FechaNot=20071013&Clasif=C&Numnot=103522 |
The Journal of Bone and Joint Surgery (American). 2007;89:2250-2259. doi:10.2106/JBJS.F.00409 © 2007 The Journal of Bone and Joint Surgery, Inc.
The Effect of Osteoclastic Activity on Tendon-to-Bone Healing: An Experimental Study in RabbitsScott
A. Rodeo, MD1, Sumito Kawamura, MD1, C. Benjamin Ma, MD1,
Xiang-hua Deng, MD1, Patrick S. Sussman, MD1, Peyton Hays, BS1
and Liang Ying, BS1
1 The Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for S.A. Rodeo:
rodeos@hss.edu
Investigation performed at The Laboratory for Soft Tissue Research, The Hospital for Special Surgery, New
York, NY
Disclosure: In support of their research for or preparation of this work, one or more of the authors received,
in any one year, outside funding or grants in excess of $10,000 from the Orthopaedic Research and Education
Foundation and the National Institutes of Health (a Pilot and Feasibility Grant as part of a NIH Core
Centers grant [1P30AR46121-01]; in addition, this investigation was conducted in a facility constructed with support
from Research Facilities Improvement Program Grant Number C06-RR12538-01 from the National Center for
Research Resources, NIH). Neither they nor a member of their immediate families received payments or other
benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid
or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center,
clinical practice, or other charitable or nonprofit organization with which the authors, or a member of
their immediate families, are affiliated or associated.
Background: Healing of a tendon graft in a bone tunnel depends on bone ingrowth into the interface
between tendon and bone. Excessive osteoclastic activity may contribute to bone resorption, tunnel widening,
and impaired healing. We hypothesized that inhibition of osteoclastic activity by osteoprotegerin (OPG) would
increase bone formation around a tendon graft in anterior cruciate ligament reconstruction in a rabbit model, while
increased osteoclastic activity due to the aplication of receptor activator of nuclear factor-kappa B
ligand (RANKL) would impair bone ingrowth.
Methods: Sixty skeletally mature, male New Zealand White rabbits underwent bilateral anterior cruciate
ligament reconstruction. OPG (100 µg per tunnel) or RANKL (10 µg per tunnel) was delivered to the tendon-bone
interface with use of a synthetic calcium phosphate carrier vehicle. Twenty animals were killed at two, four,
and eight weeks after surgery. Two rabbits from each group were prepared for histological evaluation, and the other
rabbits were used for biomechanical testing.
Results: A significantly greater amount of bone surrounded the tendon at the healing tendon-bone interface
in the OPG-treated limbs compared with the controls and the RANKL-treated limbs at all time-points (p
< 0.05). There were significantly fewer osteoclasts in the OPG-treated limbs compared with the controls and
the RANKL-treated limbs (p < 0.05). The average tunnel area in the OPG group was significantly smaller
than that in the RANKL group (p = 0.003 at two weeks and p = 0.004 at four weeks). The femur-anterior
cruciate ligament-tibia complex of the OPG-treated limbs had significantly increased stiffness compared with RANKL-treated
limbs at eight weeks (p = 0.04).
Conclusions: Osteoprotegerin significantly improves bone formation around the grafted tendon and improves
the stiffness at the healing tendon-bone junction in a rabbit model.
Clinical Relevance: Inhibition of excessive osteoclastic activity may improve tendon-to-bone healing.
http://www.ejbjs.org/cgi/content/abstract/89/10/2250
Robot-assisted endoscopic airway reconstruction in rabbits, with the aim to perform robot-assisted thoracoscopic bronchoplasty
in human subjects
Ryuichi Waseda MDa, , , Norihiko Ishikawa MD, PhDb, Makoto Oda MD, PhDa, Isao Matsumoto MD, PhDa, Yasuhiko Ohta MD, PhDa, Noriyuki Inaki MD, PhDb, Yasumitsu Hirano MD, PhDb and Go Watanabe MD, PhDa
aDepartment of General and Cardiothoracic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan
bDepartment of Telesurgery and Geomedicine, Kanazawa University School of Medicine, Kanazawa, Japan
Received
17 April 2007; revised 2 June 2007; accepted 5 July 2007. Available online 28 September 2007.
Objective
Robotic telemanipulation systems have been introduced recently to enhance the surgeon's dexterity and visualization in
endoscopic surgery and thus facilitate refined dissection, suturing, and knot tying. This study examined the technical feasibility
of performing safe and efficient robot-assisted, hand-sewn endoscopic airway reconstruction in a rabbit model.
Methods
A total of 18 tracheal anastomoses were performed in rabbits, with 6 anastomoses performed endoscopically using the da
Vinci Surgical system (Robot group), 6 anastomoses performed using traditional thoracoscopic surgical instruments (VATS group),
and 6 anastomoses performed using open surgical instruments (Open group). Anastomosis time and complications were recorded.
The effectiveness of anastomoses was evaluated by postoperative observation of all rabbits for 8 weeks and measurement of
anastomotic stricture and pathologic findings. These parameters and anastomosis time were compared between groups.
Results
In all cases in the Robot group, the procedure was completed endoscopically. No perioperative or postoperative complications
were encountered. Mean procedure time of the Robot group was 14.1 ± 2.6 minutes (mean ± standard deviation). Anastomosis time
in the Robot group was significantly shorter than in the VATS group (33.5 ± 5.2 minutes, P = .0039) and was not significantly
different in the Open group (11.4 ± 2.3 minutes, P = .1282). All anastomoses in the Robot group remained mechanically
intact, and all parameters were comparable with those of the open surgery group.
Conclusions
The technical feasibility of performing safe and efficient robot-assisted endoscopic airway reconstruction was repeatedly
demonstrated in a rabbit model. Robotic assistance significantly improved the time associated with and the quality of endoscopic
airway reconstruction.
15; 28
Abbreviations: VATS, video-assisted thoracic surgery
Address for reprints: Ryuichi Waseda, MD, Department of General and Cardiothoracic Surgery, Kanazawa University School of
Medicine, 13-1 Takaramachi, Kanazawa 920-8641, Japan.
Effect of vascular endothelial growth factor on laryngeal wound healing in rabbits http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WP4-4PJBPN2-N&_user=10&_coverDate=09%2F30%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=683b840e191ab8780509b894d5762c77
James W. Schroeder Jr MDa, b, , , Jeffrey C. Rastatter MDc and David L. Walner MDc
aChildren’s Memorial Hospital, Chicago IL
bDepartment of Otolaryngology, Northwestern University, Chicago, IL
cDepartment of Otolaryngology, Rush University Medical Center, Chicago, IL.
Received 4 February 2007;
revised 3 April 2007; accepted 26 April 2007. Available online 30 August 2007.
Objective
Study the effects of vascular endothelial growth factor (VEGF) on laryngeal wound healing in a rabbit model.
Study Design
Prospective, randomized, blinded.
Methods
The anterior cricoid cartilage of 10 rabbits was split and a VEGF-soaked collagen sponge was sewn between the cut edges.
In 10 control animals, the collagen sponge was soaked with phosphate-buffered saline solution. The larynx was harvested on
day 10. The degree of epithelial closure, the degree of soft tissue closure, and the presence of inflammatory cells was graded.
Results
There was complete epithelial closure in the control group. There was a slightly higher, but not statistically significant,
grade of soft tissue closure in the experimental group. The experimental group had a lower but not statistically significant
acute inflammatory response score.
Conclusions
The topical application of VEGF through an implanted collagen sponge to an anterior, subglottic incision in a rabbit has
no significant effect on tracheal luminal epithelial closure, acute inflammatory response, or soft tissue repair at postsurgical
day 10.
Corresponding author: James W. Schroeder, Jr, MD, Division of Pediatric Otolaryngology, Children’s Memorial Hospital,
2300 Children’s Plaza, Box 25, Chicago, IL 60614.
Pharming Sites Obtain GMP Status for Production of Drug against Hereditary Angioedema
Jul 13 2007, 11:15 AM EST
http://www.genengnews.com/news/bnitem.aspx?name=20226968
GEN News Highlights
Pharming reports that its facilities for the manufacturing of Rhucin® have successfully passed the EMEA’s inspections.
The drug is being developed to treat acute attacks of hereditary angioedema.
The EMEA has confirmed that all sites and processes that are involved in the manufacturing of Rhucin®, Pharming’s
lead product, operate according to GMP standards. This includes the company’s buildings for transgenic rabbits,
external facilities where milk and product are stored and processed, and the headquarters in Leiden as far as it is concerned
with quality aspects of Rhucin.
“Obtaining the GMP status for our facilities and processes is testimony to the hard and excellent work that our team
has put in to convert a research idea of ‘turning milk into medicine’ into a well developed and GMP-approved manufacturing
process. Our transgenic rabbit facility is the first of its kind in the world to obtain this status,” says Bruno Giannetti,
COO at Pharming.
Rhucin (recombinant human C1 esterase inhibitor) is a human protein developed through Pharming’s technology in milk
of transgenic rabbits. The disease is caused by a shortage of functional C1 esterase inhibitor in patients and results in
an over reaction of the immune system.
In Vivo Efficacy of Antimicrobial-Coated DevicesJournal of Bone and Joint Surgery (subscription) - USA
Methods: Twenty-five
rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits)
or uncoated ...
| Tracheal Traction Effects on Upper Airway Patency in Rabbits:
The Role of Tissue Pressure |
|
Kristina Kairaitis, PhD1,2,3; Karen Byth, PhD2;
Radha Parikh, PhD1,2; Rosie Stavrinou, BSc1,2; John R. Wheatley, PhD1,2,3; Terence C. Amis,
PhD1,2,3 |
1Ludwig Engel Centre for Respiratory
Research; 2Westmead Millenium Research Institute; 3University of Sydney, Westmead Hospital, Westmead,
NSW, Australia. | |
| |
 |
| |
|
Study Objectives:
To investigate the mechanisms via which lung volume related caudal
tracheal traction decreases upper airway collapsibility.
Design:
Acute physiological study
Participants:
20 male, supine, anesthetised, tracheostomised, spontaneously breathing, NZ white rabbits fitted with a sealed face
mask.
Setting: N/A
Measurements and Results:
Upper airway extraluminal tissue pressure
(ETP) was measured in the lateral (ETPlat) and anterior (ETPant) pharyngeal walls (pressure transducer tipped catheters).
Graded traction was applied to the isolated upper airway (n="17," 0-140g). Subsequently, inflation and deflation was performed
(with and without traction, 48g, n="13)" with measurement of intraluminal pressure. Upper airway transmural pressure (PTM)
was calculated (at closure and reopening) for both ETP sites (PTMlat and PTMant, respectively). A traction force of 144g decreased
ETPlat from 2.6±0.7 cm H2O (mean±SEM) to 2.1±0.7 cm H2O and ETPant from 1.1±0.4 cm H2O to 0.8±0.4 cm H2O (both P<0.001).
Increasing traction decreased closing and reopening pressures by 1.4±0.2 cm H2O for 48g of traction (n="13," P<0.0001).
In addition, 48g of traction decreased ETPlat (at closure and reopening) by 0.2±0.05 cm H2O (P<0.0001), and decreased ETPant
by 0.5±0.1 cm H2O at closing pressure and 0.8±0.1 cm H2O at reopening (both p<0.0001). Thus, for 48 g of traction, PTMlat
(at
closure and reopening) fell by 1.1±0.2 cm H2O and PTMant (reopening only) fell by 0.9±0.3 cm H2O (all P<0.0001).
Conclusions:
Since tracheal traction decreased PTMlat and PTMant by a greater amount than ETPlat and
ETPant, we conclude that the decrease in upper airway collapsibility mediated by lung volume related caudal tracheal traction
is partially explained reductions in ETP. |
Control of Aneurysm Volume by Adjusting the Position of Ligation During Creation of Elastase-Induced Aneurysms: A Prospective
StudyY.H. Dinga, D. Daia, M.A. Danielsona,
R. Kadirvela, D.A. Lewisa, H.J. Clofta and D.F.
Kallmesa
a From the Neuroradiology Research Laboratory, Department of Radiology, Mayo Clinic and Foundation,
Rochester, Minn
Please address correspondence to David F. Kallmes, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905;
e-mail: kallmes.david@mayo.edu
BACKGROUND AND PURPOSE: Animal models with appropriate volume are crucial for preclinical
assessment of aneurysm therapies. Our purpose was to control the aneurysm volume by adjusting the position
of ligation during creation of elastase-induced aneurysms in rabbits.
MATERIALS AND METHODS: Sixty elastase-induced aneurysms in rabbits were created. Two different methods
were used for creation, including group 1 (n = 30) by using a lower ligation (from the origin
of the right common carotid artery [RCCA] to the ligation point, 10 mm) and group 2 (n = 30) by using a
higher ligation (from the origin of the RCCA to the ligation point, 15 mm). Aneurysm sizes (neck diameter,
width, and height) and volumes in the 2 groups were measured and calculated, and they were compared
by using the Student t test.
RESULTS: The mean aneurysm neck diameter, width, and height for group 2 were significantly larger than
those of group 1 (3.3 ± 0.8 versus 2.7 ± 0.6 mm, P < .001; 3.7 ± 0.7 versus 2.5 ± 0.7 mm,
P < .001; 9.0 ± 1.7 versus 7.3 ± 1.9 mm, P < .001, respectively). The aneurysm volume
in group 2 was significantly larger than that in group 1 (102.4 ± 54.8 mm3 versus 36.6 ± 26.8
mm3, P < .001).
CONCLUSION: The aneurysm volume of elastase-induced models in rabbits can be controlled by adjusting
the position of the ligation. Using a higher ligation can create relatively more voluminous aneurysms,
compared with using a lower ligation.
http://www.ajnr.org/cgi/content/abstract/28/5/857
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