Stem cells for diabetic ulcers

A new method could be used to heal ischemic wounds in diabetic patients. Researchers from the University of Bristol and the Istituto Neurologico Besta in Italy report that the administration of stem cells stimulates healing responses in animal models that reproduced the human diabetic condition.

When organic tissues suffer from a lack of oxygen (ischemia) – as it happens during a heart attack or in the process of diabetic gangrene – they undergo necrosis. Spontaneous healing responses can be experimentally induced either by administering specific growth factors or by transplanting Vascular Progenitor Cells (VPCs) – cells that undergo a targeted differentiation under selected stimuli.

Vascular Progenitor Cells were recently identified in the foetal aorta by Paolo Madeddu, from Bristol University, Bristol (UK), and Giulio Alessandri from the Istituto Neurologico Besta of Milan (Italy), and attracted the researchers’ interest for there ability to form mature vascular-like structures in vitro, and to stimulate vascular and skeletal regeneration in vivo.

After generating some ulcers in limbs made ischemic by artery occlusion, the researchers applied human VPCs directly onto the wound and observed a marked reduction in the lesion size, after three and seven days. “In addition,” points out Madeddu, “we noted that these cells increased the de novo vessels formation in the wounded site (as well as arteriole density). VPCs transplantation resulted in an acceleration of wound closure, especially in the initial phase of tissue recovery.”



Flu virus gene plotted

Researchers have determined the full genetic sequence of more than 200 distinct strains of human influenza virus. The information, being made available in a publicly accessible database, is expected to help scientists better understand how flu viruses evolve, spread and cause disease.

The genomic data already has enabled scientists to determine why the 2003-4 annual influenza vaccine did not fully protect individuals against the flu that season. The new genomes are the initial results of the Influenza Genome Sequencing Project, a joint effort of the US National Institute of Allergy and Infectious Diseases (NIAID), and multiple partners.

“These new data give us the most comprehensive picture to date of how influenza viruses evolve and are transmitted throughout human populations,” says NIAID Director Anthony S. Fauci, MD. “This information could help us to make more effective vaccines, therapeutics and diagnostics against a disease that claims some 36,000 American lives each year.”

“Through the Influenza Genome Sequencing Project, techniques have been established to allow rapid sequencing of full genomes of influenza virus. This project continues to move toward our goal of revealing complete genetic blueprints of thousands of known human and avian influenza viruses over the next several years,” says Maria Giovanni, PhD, who oversees NIAID's flu genome sequencing project.



Workers shun vaccine

Low flu vaccination rates among healthcare workers could be risking the lives of frail elderly patients and increasing winter pressures in UK hospitals, according to research published in the latest issue of Journal of Clinical Nursing.

Less than 8% of nurses and healthcare assistants surveyed in two Liverpool hospitals said they had annual flu injections. In addition, 29% of the 144 healthcare workers who took part in the study said they didn’t feel they needed to be vaccinated, 18% were not aware of the vaccine and 11% were concerned about the side effects.

“Vaccinating healthcare workers against flu can reduce staff sickness and winter pressures as well as reducing deaths among frail older patients” says Dr Helen Canning, who carried out her research at the University of Liverpool.

“Our study found that the main reason for poor vaccine uptake was a basic lack of knowledge and understanding of the vaccine, especially regarding benefits and side-effects.

“Almost half of the respondents were either not aware of the vaccine or did not think they needed it. And only 10% knew that the benefits of the vaccine included protecting patients against the serious complications of flu.

Dr Canning and her co-researchers – Dr Jennifer Phillips and Specialist Registrar Stephen Allsup – also looked at sick leave rates among the respondents. They found that in the three months before the survey more than 51% of respondents had taken sick leave because of a flu-like illness.

“If the vaccine uptake had been more widespread, illnesses due to the influenza virus could have been prevented,” says Dr Canning. “This illness prevention, if repeated in all hospitals nationwide, could have a significant impact on ward staffing issues during the busy winter months when the incidence of flu is greatest.”



Old drug, new hope

While people in third world countries are ‘dying for new medicines’ against tropical killer diseases such as malaria, La Trobe University malaria researchers believe there may be a way to bring back one of the oldest antimalarial drugs to combat the most dangerous of the malaria parasites – at a cost much less than for new drugs.

Head of a La Trobe University malaria research group, Professor of Biochemistry, Leann Tilley, says her group, in association with the Liverpool School of Tropical Medicine in the UK, is investigating an antimalarial drug combination that might make this possible.

“We are studying the mechanism of action of the antimalarial drug, chloroquine, which was for many decades an indispensable part of our armoury against the most deadly of the malaria parasites, Plasmodium falciparum.

“Unfortunately chloroquine has now been rendered useless by parasite resistance. Another antimalarial drug, primaquine, is already licensed for treating a less virulent form of malaria caused by Plasmodium vivax.” Professor Tilley says chloroquine-resistant parasites have evolved a mutant transport protein that expels chloroquine via a pore in the membrane of the parasite's food vacuole.

“We believe that primaquine, which has a similar structure to chloroquine, binds to the same transport protein, but can't be extruded via the pore. As primaquine competitively displaces chloroquine the parasite is no longer able to expel chloroquine, and thus is killed,” said Tilley.

The main advantage of chloroquine-primaquine combinations compared with other possible combinations is the low cost. Treatment with chloroquine costs about ten cents (US) and primaquine about 15 cents. By comparison newer drugs, such as the artemisinin derivatives, cost about US$3 and need to be used in combination with other expensive drugs.



Nobel Prize

The Nobel Assembly at Karolinska Institutet awarded The Nobel Prize in Physiology or Medicine for 2005 jointly to Barry J Marshall and J Robin Warren for their discovery of “the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”.

This year's Nobel Laureates in Physiology or Medicine made the remarkable and unexpected discovery that inflammation in the stomach (gastritis) as well as ulceration of the stomach or duodenum (peptic ulcer disease) is the result of an infection of the stomach caused by the bacterium Helicobacter pylori.

Robin Warren, a pathologist from Perth, Australia, observed small curved bacteria colonising the lower part of the stomach (antrum) in about 50% of patients from which biopsies had been taken. He made the crucial observation that signs of inflammation were always present in the gastric mucosa close to where the bacteria were seen. Barry Marshall, a young clinical fellow, became interested in Warren's findings and together they initiated a study of biopsies from 100 patients. After several attempts, Marshall succeeded in cultivating a hitherto unknown bacterial species (later denoted Helicobacter pylori) from several of these biopsies.

Together they found that the organism was present in almost all patients with gastric inflammation, duodenal ulcer or gastric ulcer. Based on these results, they proposed that Helicobacter pylori is involved in the aetiology of these diseases.

Even though peptic ulcers could be healed by inhibiting gastric acid production, they frequently relapsed, since bacteria and chronic inflammation of the stomach remained. In treatment studies, Marshall and Warren as well as others showed that patients could be cured from their peptic ulcer disease only when the bacteria were eradicated from the stomach.

 Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors.



Mammography trial results

Results of a US study have shown that women with dense breasts, women younger than 50, and those who are perimenopausal may benefit from digital mammograms.

Preliminary results from a large, clinical trial of digital versus film mammography show no difference in detecting breast cancer for the general population of women in the trial.

However, those women with dense breasts, who are pre- or perimenopausal (women who had a last menstrual period within 12 months of their mammograms), or who are younger than age 50 may benefit from having a digital rather than a film mammogram.

The results were reported 16 September, 2005 in a special online publication of the New England Journal of Medicine and at a meeting of the American College of Radiology Imaging Network (ACRIN) in Pentagon City.

The trial, sponsored by the National Cancer Institute was conducted by a network of researchers led by ACRIN. Secondary goals measuring the relative cost-effectiveness of both digital and film technologies, and the effect on participant quality of life due to the expected reduction of false positives, are still being assessed and will be reported at a later date.



Community MRSA

A study of how the immune system reacts to strains of antibiotic-resistant Staphylococcus aureus bacteria – emerging strains that sicken otherwise healthy people, or so-called “communityacquired” infections – has shown for the first time that these strains are more deadly and better at evading human immune defenses than more common S aureus strains that originate in hospitals and other healthcare settings.

In a paper released online in The Journal of Immunology, scientists from the US National Institute of Allergy and Infectious Diseases (NIAID describe how communityacquired “S aureus” strains that survive treatment with the methicillin family of antibiotics can evade immune defenses.

Infections from community-acquired methicillin-resistant S aureus, or MRSA, are difficult to treat and are increasing nationally at an alarming rate, say experts. Scientists at NIAID's Rocky Mountain Laboratories in Hamilton, US, and colleagues examined the ability of MRSA strains to cause disease in mice and avoid destruction by human white blood cells called neutrophils. Neutrophils, which typically ingest and then kill harmful bacteria, make up about 60% of all white blood cells and are the first line of defense against bacteria.

Scientists know that community-acquired strains differ from hospital strains, but they don't know why the community strains cause more serious infection in otherwise healthy people.



Spray-on skin for burns

The first controlled clinical study to examine the effectiveness of sprayed cultured skin cells to close the wounds of burns victims is being undertaken at the Queen Victoria Hospital NHS Foundation Trust (QVH), East Grinstead, UK. Phil Gilbert, consultant plastic surgeon and burns specialist, said: “In pilot studies we get the impression that wounds heal noticeably quicker with less scarring using this spray on method with skin cells.

We now need to quantify how good it is at saving lives, repairing wounds and reducing the cost of caring for burns victims to the NHS.” Skin cells have been grown in laboratory conditions since the mid-1970s, but until now there has not been a significant scientifically- controlled study.

Dr Liz James, a cell culture scientist and head of research at the Blond McIndoe Centre for medical research, based at QVH, said: “We will be conducting the multi-centre study on two groups of patients; 24 adults with severe burns and 50 children aged between 12 and 36 months with scalds.

We have seen what I can only describe as miraculous results using spray on skin with patients surviving 90% burns who otherwise had very little chance of survival.”



Chronic disease alarm

The World Health Organisation (WHO) report Preventing Chronic Diseases: a vital investment says global action to prevent chronic disease could save the lives of 36 million people who would otherwise be dead by 2015.

Currently, chronic diseases are by far the leading cause of death in the world and their impact is steadily growing. The report projects that approximately 17 million people die prematurely each year as a result of the global epidemic of chronic disease.

Faced with the prospect of millions of people dying prematurely and suffering needlessly from heart disease, stroke, cancer and diabetes, WHO says the global epidemic of chronic disease must be stopped.

Contrary to common perception, this largely invisible epidemic is worst in low and middle income countries, where 80% of all chronic disease deaths occur. The report details the latest findings from nine countries: Brazil, Canada, China, India, Nigeria, Pakistan, the Russian Federation, the United Kingdom and the United Republic of Tanzania.

The report also provides new projections for the economic impact of chronic diseases. For example, China, India and the Russian Federation could forego billions of dollars in national income over the next ten years as a result of heart disease, stroke, cancer and diabetes. The estimated accumulated losses to China from 2005 to 2015 are US$558 billion, for India US$236 billion, and US$303 billion for the Russian Federation.

In the report, WHO proposes a new global goal: to reduce the projected trend of chronic disease death rates by 2% each year until 2015. This would prevent 36 million people dying of chronic diseases in the next 10 years, nearly half of them before they turn 70. But these problems and their solutions lie outside the control of any one sector.

In order to achieve the goal, all sectors from government, private industry, civil society and communities will have to work together.



Father time

The parts of the genetic make-up that are thought to determine an individual’s maximum possible longevity, so-called telomeres, are inherited from the father but not the mother.

This is shown by a research team at Umeå University, Sweden, which was due to be published in the US scientific journal Proceedings of the National Academy of Sciences. Telomeres are genetic material with repetitive content at the ends of DNA, and their main function is believed to be to protect the rest of the genetic material from degradation.

Telomeres are shortened each time a cell divides, which in broad terms means that the longer a cell’s telomeres are, the longer the individual can live, in theory. A person’s telomeres are shortened with age, which the findings of the study indeed show: telomeres were shortened by an average of 21 nitrogen base pairs per year in the subjects studied.

The study was carried out on 132 healthy subjects in 49 different families with no close kinship to each other in northern Sweden. The subjects consisted of fathers and mothers (mean age 66 years) and their daughters and sons (mean age 37 years). Blood samples were taken, and mononuclear immune cells were culled.

Half of these were simply frozen, while the other half were infected with Epstein- Barr virus (EBV) and cultured for 18-55 days, whereupon the surviving cells were frozen. DNA was then extracted from both cell types using standardised techniques, and the length of the telomeres was ascertained.

The findings show that changes in the length of the telomeres in the cultured cells are determined by the original length of the telomeres, and the length of the telomeres in the second generation, both sons and daughters, proved to be inherited from the father.

The work was carried out by doctoral candidate Katarina Nordfjäll and Professor Göran Roos at the Division of Pathology, Department of Medical Biosciences, Umeå University, and Research Engineer Åsa Larfalk, Statistician Petter Lindgren, and Professor Dan Holmber, all three at the Division of Medical and Clinical Genetics, Department of Medical Biosciences, Umeå University.

The article can be downloaded from:
www.umu.se/medfak/forskning/PNAStelomerer-24-okt.pdf

                                  
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