Alzheimer's Found To Be More Aggressive Among Younger Elderly But Slows In Advanced Age

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Main Category: Alzheimer's / Dementia
Also Included In: Seniors / Aging
Article Date: 05 Aug 2012 - 0:00 PDT Current ratings for:
Alzheimer's Found To Be More Aggressive Among Younger Elderly But Slows In Advanced Age

The greatest risk factor for Alzheimer's disease (AD) is advancing age. By age 85, the likelihood of developing the dreaded neurological disorder is roughly 50 percent. But researchers at the University of California, San Diego School of Medicine say AD hits hardest among the "younger elderly" - people in their 60s and 70s - who show faster rates of brain tissue loss and cognitive decline than AD patients 80 years and older.

The findings, reported online in the journal PLOS One, have profound implications for both diagnosing AD - which currently afflicts an estimated 5.6 million Americans, a number projected to triple by 2050 - and efforts to find new treatments. There is no cure for AD and existing therapies do not slow or stop disease progression.

"One of the key features for the clinical determination of AD is its relentless progressive course," said Dominic Holland, PhD, a researcher at the Department of Neurosciences at UC San Diego and the study's first author. "Patients typically show marked deterioration year after year. If older patients are not showing the same deterioration from one year to the next, doctors may be hesitant to diagnose AD, and thus these patients may not receive appropriate care, which can be very important for their quality of life."

Holland and colleagues used imaging and biomarker data from participants in the Alzheimer's Disease Neuroimaging Initiative, a multi-institution effort coordinated at UC San Diego. They examined 723 people, ages 65 to 90 years, who were categorized as either cognitively normal, with mild cognitive impairment (an intermediate stage between normal, age-related cognitive decline and dementia) or suffering from full-blown AD.

"We found that younger elderly show higher rates of cognitive decline and faster rates of tissue loss in brain regions that are vulnerable during the early stages of AD," said Holland. "Additionally cerebrospinal fluid biomarker levels indicate a greater disease burden in younger than in older individuals."

Holland said it's not clear why AD is more aggressive among younger elderly.

"It may be that patients who show onset of dementia at an older age, and are declining slowly, have been declining at that rate for a long time," said co-author Linda McEvoy, PhD, associate professor of radiology. "But because of cognitive reserve or other still-unknown factors that provide 'resistance' against brain damage, clinical symptoms do not manifest till later age."

Another possibility, according to Holland, is that older patients may be suffering from mixed dementia - a combination of AD pathology and other neurological conditions. These patients might withstand the effects of AD until other adverse factors, such as brain lesions caused by cerebrovascular disease, take hold. At the moment, AD can only be diagnosed definitively by an autopsy. "So we do not yet know the underlying neuropathology of participants in this study," Holland said.

Clinical trials to find new treatments for AD may be impacted by the differing rates, researchers said. "Our results show that if clinical trials of candidate therapies predominately enroll older elderly, who show slower rates of change over time, the ability of a therapy to successfully slow disease progression may not be recognized, leading to failure of the clinical trial," said Holland. "Thus, it's critical to take into account age as a factor when enrolling subjects for AD clinical trials."

The obvious downside of the findings is that younger patients with AD lose more of their productive years to the disease, Holland noted. "The good news in all of this is that our results indicate those who survive into the later years before showing symptoms of AD will experience a less aggressive form of the disease."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alzheimer's / dementia section for the latest news on this subject. Co-authors are Rahul S. Desikan, Department of Radiology, UCSD and Anders M. Dale, Departments of Neurosciences and Radiology, UCSD.
Funding for this research came, in part, from the National Institutes of Health (grants R01AG031224, R01AG22381, U54NS056883, P50NS22343 and P50MH08755); the National Institute on Aging (grant K01AG029218) and the National Institute of Biomedical Imaging and Bioengineering (grant T32EB005970).
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First Indication Of People Naturally Protected Against Rabies Found In Remote Amazonian Communities

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Main Category: Tropical Diseases
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 03 Aug 2012 - 0:00 PDT Current ratings for:
First Indication Of People Naturally Protected Against Rabies Found In Remote Amazonian Communities

Challenging conventional wisdom that rabies infections are 100 percent fatal unless immediately treated, scientists studying remote populations in the Peruvian Amazon at risk of rabies from vampire bats found 11 percent of those tested showed protection against the disease, with only one person reporting a prior rabies vaccination. Ten percent appear to have survived exposure to the virus without any medical intervention. The findings from investigators at the U.S. Centers for Disease Control and Prevention (CDC) were published in the August 2012 issue of the American Journal of Tropical Medicine and Hygiene.

"The overwhelming majority of rabies exposures that proceed to infections are fatal. However, our results open the door to the idea that there may be some type of natural resistance or enhanced immune response in certain communities regularly exposed to the disease," said Amy Gilbert with the CDC's National Center for Emerging and Zoonotic Infectious Diseases, who is the paper's lead author. "This means there may be ways to develop effective treatments that can save lives in areas where rabies remains a persistent cause of death."

Rabies experts estimate the disease kills 55,000 people each year in Africa and Asia alone, and appears to be on the rise in China, the former Soviet Republics, southern Africa, and Central and South America. According to the CDC, in the United States, human deaths from rabies have declined over the past century from 100 annually to an average of two per year thanks to an aggressive campaign to vaccinate domestic animals against the disease.

In general, people who believe they may have been exposed to rabies are advised to immediately seek treatment which involves post-exposure prophylaxis (PEP) - a series of injections - to prevent the exposure from causing an active infection. These preventive treatments, when administered promptly, are 100 percent successful at preventing disease. Scientists have documented only a small number of individual cases, including one last year in California, in which an exposure to rabies proceeded to infection and the victim survived. Most of those survivors still required intensive medical attention, including one case in Wisconsin in which doctors induced a coma, though this approach has not been successful in most subsequent cases.

This CDC study was conducted in collaboration with the Peruvian Ministry of Health as part of a larger project to understand better bat-human interactions and its relation to rabies and emerging diseases that may be transmitted by bats. For their research, scientists traveled to two communities (Truenococha and Santa Marta) in a remote section of the Peruvian Amazon where outbreaks of fatal infections with rabies caused by bites from vampire bats - the most common "natural reservoir" for the disease in Latin America - have occurred regularly over the last two decades. They interviewed 92 people, 50 of whom reported previous bat bites. Blood samples were taken from 63 individuals and seven (11 percent) were found to have "rabies virus neutralizing antibodies."

One out of the seven individuals reported receiving a rabies vaccination - which generates antibodies to the rabies virus?"but there was no evidence that the other six had received anti-rabies vaccine prior to the blood sampling or had sought out any medical attention for a bat bite, evidence that they had harbored the virus itself.

The researchers acknowledged that they could not conclusively determine whether the antibodies were caused by an exposure to the virus that was somehow insufficient to produce disease. But they believe their evidence "suggests that (rabies virus) exposure is not invariably fatal to humans."

Gilbert said non-fatal exposures may happen more often than some think because "unless people have clinical symptoms of the disease they may not go to the hospital or clinic, particularly where access is limited."

"We all still agree that nearly everyone who is found to be experiencing clinical symptoms of rabies dies," Gilbert said. "But we may be missing cases from isolated high-risk areas where people are exposed to rabies virus and, for whatever reason, they don't develop disease."

In the Amazon region where the study was conducted - the Province Datem del Maranon in the Loreto Department of northern Peru - vampire bats, which live off of mammalian blood, regularly come out at night and prefer to feed on livestock. But in the absence of those food sources, they are known to seek out a meal from humans. They can use their extremely sharp teeth and the anticoagulant that naturally occurs in their saliva (appropriately referred to as "draculin") to feed on a sleeping person without awakening them. The rabies virus circulates extensively among vampire bat colonies in the region, and when an infected bat feeds, it passes along the virus to its host.

"This type of thorough and persistent scientific rabies investigation lends continued support to the belief that even the most dangerous of infectious diseases may be amenable to treatment," said James W. Kazura, MD noted infectious disease expert and president of the American Society of Tropical Medicine and Hygiene (ASTMH). "Continued investment of resources is essential for us to protect the health and well-being of innocent people whose lives and livelihoods are needlessly threatened by infectious diseases like rabies."

Gilbert and her colleagues hope their findings will prompt further studies in remote, at-risk communities to see if the results are replicated. In an editorial accompanying the study, Rodney E. Willoughby, a pediatric disease specialist at Children's Hospital of Wisconsin, said if it turns out there are distinct populations of people with "complete or relative resistance to rabies," there could be the potential to use whole genome sequencing to help develop new, life-saving treatments for rabies infections.

"Careful, respectful genetic study of these genetically unique populations may provide information on which pathways in human biochemistry and physiology promote resistance to human rabies," he wrote. "Equally important, knowing that there is a continuum of disease, even for infectious diseases like rabies, should push us harder to try for cures when confronted by so-called untreatable infectious diseases...."

Gilbert noted that the study was done as part of a larger public health effort to address a series of rabies outbreaks in the Amazon, where some health officials are now considering conducting pre-emptive vaccination campaigns in areas where risk of rabies is high and availability of medical care low. She said that while her study highlights people who appear to have survived an exposure to the virus, the fact remains that rabies outbreaks in small communities in the region have left tragic results.

"These are very small villages and, when they witness ten people dying from what is a horrible disease, it is incredibly traumatic," Gilbert said. "We want to help raise awareness of the problem and try to develop a more proactive response."

Article adapted by Medical News Today from original press release. Source: Burness Communications
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Cellular Processing Of Proteins Found In Congolese Child Birthing Tea

Main Category: Nursing / Midwifery
Also Included In: Women's Health / Gynecology
Article Date: 13 Dec 2011 - 1:00 PST

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Many plants produce compounds that serve as a defense against predators or pathogens. Some are also used by humans for a variety of beneficial purposes, such as in medicines. As recently as the early 1990s, a unique class of proteins previously unknown to science, the cyclotides, was discovered. First noted through African tribal use as a tea given to speed up delivery during childbirth, cyclotides have since been determined to serve as a powerful insecticidal and nematocidal defense in the plants that produce them, and they also have anti-HIV and antimicrobial properties, with obvious benefits for humans. However, scientists are still working on unlocking much of the basic science of these fascinating proteins, including how they work and where in the plant cell they are produced.

Among the scientists interested in cyclotides, as well as other immune proteins, is Marilyn Anderson of LaTrobe University, Australia.

"Cyclotides are small cyclic peptides of only 28-37 residues that most plant biologists may not have heard of, yet they form the largest family of cyclic proteins described to date in any organism," explains Anderson. "Cyclic cyclotides are widespread in members of the Rubiaceae, Violaceae, Cucurbitaceae and Fabaceae families, yet linear cyclotides are also produced by major monocots such as rice, corn and barley."

"The big question is what do they do?" she continues. "We have discovered that some are potent insecticidal and nematocidal molecules but it is likely that some have other functions as yet undescribed."

Indeed, cycolotides have a unique shape resulting from three disulfide bonds and a peptide backbone that twists in such as way as to produce a cystine knot. This cyclic configuration provides the protein with a very stable structure that is hard to break down - which is how it maintains its bioactivity despite, for example, the high temperatures used to brew the tea used to aid childbirth in the Congo.

"The tea, called kalata kalata, was prepared by boiling the leaves so the active constituent had to be stable to boiling, as well as passage through the human intestinal tract where sufficient amounts were absorbed into the bloodstream to stimulate the uterus," comments Anderson. "Some years after its use was noted, in 1995, the structure of kalata B1, the active constituent from the tea, was solved and its cyclic structure was discovered."

Since then, Anderson, in collaboration with other researchers, has discovered that cyclotides are gene encoded - and in fact are encoded by a single gene, which was at the time unique for a cyclic protein from a eukaryote - and continues to investigate how plants make these cyclic peptides. Her most recent discovery is published in the December issue of the American Journal of Botany. She and her colleagues successfully determined where in the plant cell the cyclotide kalata B1 is produced and how its precursor protein, Oak1, is directed to the appropriate processing location*.

Kalata B1 is found in the leaves of Oldenlandia affinis (Rubiaceae) and, as with all proteins, is made up of building blocks of amino acids put together in a genetically determined sequence. The precursor protein to kalata B1, called Oak1, is linear and is made up of a series of domains, the centerpiece of which contains a cyclotide domain sandwiched between the N- and C-terminal segments. Other cyclotide precursors may contain up to three cyclotide domains.

Anderson and co-authors used a novel approach to determine where in the plant cell the precursor protein was sent and which segment contained the signal sequence responsible for directing it there. They split the precursor protein Oak1 up into its component parts and tagged each segment with the green fluorescent protein (GFP). They then transferred the different constructs into Agrobacterium, injected the Agrobacterium into living leaves of Nicotiana benthamiana, and two days later injected a dye to visually highlight the plasma membrane and the intracellular membranes, such as the tonoplast, which surrounds the vacuole.

Their first finding was that the precursor protein Oak1 was sent to the vacuole to be processed. When viewed under a microscope, cells that were injected with the Oak1-GFP construct had vacuoles that were entirely filled with florescent green dye.

This was a very exciting finding because enzymes hypothesized to play a key role in the ring formation of cyclotides are naturally found in the vacuole. These two pieces of information led the authors to conclude that the vacuole must be the location where Oak1 is converted into kalata B1.

But how is the precursor protein directed to the vacuole?

When the authors looked at cells injected with the different constructs, they found that the only cells that had green florescent vacuoles were those containing constructs with segments of the Oak1 precursor protein that contained propeptides from the N-terminal region. Thus, while the C-terminal segment of the precursor protein is critical for the formation of the ring structure, the N-terminal segments get it to the appropriate cyclization processing location.

Knowing precisely how the precursor protein is directed to its target location (the vacuole) where the cyclotide domain is excised and the ligation of the N- and C- termini occurs is a critical step in understanding the biology of these proteins.

"After conducting the research described in this paper," Anderson concludes, "we now know that the cyclization reactions occur in the vacuole and this provides more insight into the pH conditions required for cyclization and supports our hypothesis that the vacuolar enzyme asparaginyl endoproteinase is the crucial enzyme involved."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our nursing / midwifery section for the latest news on this subject. Conlan, Brendon F., Amanda D. Gillon, Barbara L. Barbeta, and Marilyn A. Anderson. (2011). Subcellular targeting and biosynthesis of cyclotides in plant cells. American Journal of Botany 98(12): 2018-2026. DOI: 10.3732/ajb.1100154 The full article in the link mentioned is available for no charge for 30 days following the date of this summary at http://www.amjbot.org/content/98/12/2018.full.pdf+html. American Journal of Botany Please use one of the following formats to cite this article in your essay, paper or report:

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Potential Breast Cancer Prevention Agent Found To Lower Levels Of 'Good' Cholesterol Over Time

Main Category: Breast Cancer
Also Included In: Cholesterol
Article Date: 10 Dec 2011 - 0:00 PST

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Exemestane steadily lowered levels of "good" cholesterol in women taking the agent as part of a breast cancer prevention study, say researchers at Georgetown Lombardi Comprehensive Cancer Center. Exemestane, an aromatase inhibitor used to treat estrogen receptor-positive breast cancer, is being tested to prevent breast cancer in women at an increased risk of developing the disease.

Georgetown researchers say their findings, presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), suggest that the effect this agent has on blood lipids may prove to be significant for women at high risk for heart disease due to elevated blood cholesterol, although no such effects have been seen yet in patients studied over two years of treatment.

There are two types of cholesterol transported in our blood - HDL and LDL. HDL cholesterol is known as "good" cholesterol, because high levels of it protect against heart attack. LDL cholesterol is known as "bad" cholesterol because it can buildup in the inner walls of the arteries that feed the heart and brain, and lead to atherosclerosis.

"Lower levels of the HDL, the good cholesterol, have been shown to increase the risk of heart attack and stroke. While we found that exemestane lowers good cholesterol levels, the clinical significance of this decrease is unknown," says a study investigator, Margaret Gatti-Mays, M.D. an intern in internal medicine at Georgetown.

The results come from a phase II multi-institutional study of women at increased risk for breast cancer that evaluated the safety and efficacy of exemestane over two years of therapy. The findings, from 31 patients, showed that the absolute change from the baseline HDL level at 3, 12, and 24 months were -8.0 mg/dL, -8.5 mg/dL, and -9.9 mg/dL, respectively. The rest of the lipid panel, including LDL (the bad cholesterol) was relatively unchanged.

"It is notable that both women taking and not taking lipid-lowering medication had decreases in HDL," Gatti-Mays says.

"Lower HDL levels are associated with an increased risk of heart disease, so if a patient has a low HDL level, exemestane may not be the best choice as a breast cancer prevention agent," says the study's senior investigator, Jennifer Eng-Wong, M.D., senior medical director of the Capital Breast Care Center at Georgetown Lombardi Comprehensive Cancer Center.

She adds that other anti-estrogen therapies designed to prevent breast cancer don't appear to lower HDL. "Less data is available on anastrozole and letrozole, which are other aromatase inhibitors, but they do not appear to lower HDL. Conversely, tamoxifen has an overall favorable effect on cholesterol."

"Exemestane has been shown to be an effective therapy in the prevention of breast cancer in postmenopausal women who have an increased risk of developing it. This study adds information that will help individualize care for these women though larger studies are needed to more fully evaluate the impact of exemestane on cholesterol and cardiovascular health," says Gatti-Mays.

The research was conducted at Georgetown and the National Cancer Institute (NCI), and was supported by both institutions, as well as the National Institutes of Health, and Pfizer Inc. (which supplied exemestane). (OVER)

A recipient of the ACCR Scholar-in-Training Award, Gatti-Mays' travel to the SABCS conference was funded by this award which is supported by Susan G. Komen for the Cure. She reports no personal financial interests related to the study.

The 2011 CTRC-AACR San Antonio Breast Cancer Symposium is presented by the Cancer Therapy & Research Center at UT Health Science Center San Antonio, the American Association for Cancer Research, and Baylor College of Medicine.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

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