Medicine Man

Cancer of the liver is very difficult to detect, and it is a major cause of death in Asia and Africa, with rising incidence in Western countries as well.

Now, VIB researchers connected to Ghent University, in collaboration with research centers in Beijing and Shanghai in China, have developed a test to detect liver cancer in an early stage. A small blood sample is the only requirement for the test. The new test enables accurate detection of liver cancer in over 50% of the cases for which previous diagnostic tests have not been able to provide a definitive answer.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. The disease most often appears following a chronic inflammation of the liver as a consequence of a hepatitis B or C virus infection or cirrhosis of the liver. Cirrhosis of the liver comprises a group of liver diseases in which the normal liver cells become damaged and are replaced by scar tissue. This reduces the amount of healthy liver tissue, and the accumulation of scar tissue disrupts the development and functioning of this complex organ. Cirrhosis of the liver has various causes, including: excessive use of alcohol, chronic viral hepatitis B, C and D infections, diseases of the bile ducts, and parasitic infections.

Half a million patients die every year in China because of cirrhosis of the liver or liver cancer. 60% to 80% of the patients with liver cancer have a previous history of cirrhosis of the liver. In Belgium as well, 350 new cases of liver cancer occur each year. Transplantation often offers the only possible remedy. Detection methods that would detect HCC in an early stage would save many lives.

Methods of detecting malignant growths are often based on the concentration of particular substances called 'markers' present in the blood. For the detection of HCC, only one marker (AFP) is generally used. However, this marker has a low specificity and is frequently inadequate because of false-positive results.

A new test for detecting HCC was developed by Xue-en Liu, Liesbeth Desmyter and colleagues under the supervision of Cuiying Chen (Chitty) in collaboration with scientists in China. This test is based on previous work of Prof. em. Roland Contreras and Nico Callewaert.

By examining blood concentrations in Chinese patients with cirrhosis of the liver due to a hepatitis B virus infection, they found that the quantities of two particular sugar groups that appear on the blood proteins varied according to the stage of the disease. Furthermore, these values correlated with the size of the tumor. The ratio of these values forms the basis of the new blood test. The researchers were able to make the correct diagnosis in 70% of the cases - a success rate that equals that of the AFP tumor marker currently being used in the clinic.

When the AFP test is used in combination with the new test, the accuracy of HCC diagnosis rises dramatically. The new test succeeds in detecting liver cancer in more than half of the patients with cirrhosis of the liver for which the AFP test provides no answer. This test would allow frequent and non-invasive analyses to be carried out on cirrhosis patients, which would enable scientists to detect liver cancer in an earlier stage and to closely monitor the development of the disease.

At the moment, the researchers are working on implementing this test for the diagnosis of liver disease in compliance with clinical practice. The new results concerning HCC diagnosis provide an extra incentive for pursuing this development as intensively as possible.

http://www.vib.be

UK estimates of 'drug-related deaths' (DRDs) include mortalities of drug abusers and non-drug abusers.

So these figures may not be the best way of monitoring the performance of Drug and Alcohol Action Teams, a study published in the online open access journal Substance Abuse Treatment, Prevention and Policy suggests.

DRDs are currently used to help evaluate the success of Drug and Alcohol Action Teams in England and Wales, but the term's exact meaning varies according to European and national definitions. This means it is hard to know what sorts of deaths are included, the demographic profile of those who died, and whether or not individuals were tapped in to services designed to assist drug abusers.

Dr. Caryl Beynon from Liverpool John Moores University and colleagues studied details of 70 DRDs that occurred over an 18 month period in Liverpool - the UK city with the highest recorded number of DRDs in 2004.

They found their sample included drug abusers and non-drug abusers. The latter tended to be older, had no recent contact with drug-related agencies, and had different post-mortem drug profiles - they were more likely to have died from the toxic effects of anti-depressants, anti-psychotics and analgesics than from taking 'problematic' drugs (e.g. heroin, crack cocaine/cocaine). Generally the figures also excluded deaths related to drug misuse, such as those caused by bacterial and viral infections via sharing drug injecting equipment or contaminated drugs. DRD figures don't capture the true burden of drug-related mortality as the figures include a wide range of disparate deaths and exclude others which are clearly related to the abuse of drugs, the authors conclude.

http://www.biomedcentral.com

Many common diseases exhibit gender bias and gender differences have been observed in the development of high blood pressure (hypertension) and heart (cardiovascular) disease.

Previous studies have reported that gender may affect vascular physiology and the body's response to some types of blood pressure medications. Although gender is usually accounted for in association studies, newer research has focused on identifying autosomal (not on the X or Y chromosomes) genes that contribute differentially to complex traits (blood pressure) or diseases (hypertension). In a new study, researchers examined the differential contribution of genetic factors involved in regulating blood pressure based on samples drawn from a large community. They found significant differences in genetic contributors to blood pressure in males versus females.

The study was conducted by Brinda Rana and Nicholas Schork, Department of Psychiatry; Paul Insel, Department of Pharmacology; and Daniel O'Connor, Department of Medicine; University of California, San Diego, La Jolla, CA. It is entitled, "Population Extremes-Based Approach Defines Gender Differences in Adrenergic and Renal Genes Contributing to Blood Pressure." The research is one of more than 100 presentations being offered at the conference, Sex and Gender in Cardiovascular-Renal Physiology and Pathophyiology, being held August 9-12, 2007 in Austin, TX. The event is the second scientific gathering to be sponsored by the American Physiological Society (APS; www.The-APS.org) this year.

Methodology

The researchers used a study design in which they sampled age-matched Caucasian Americans (611 male and 656 female) within the top and bottom fifth percentile of blood pressure against blood pressure measured in more than 53,000 people during routine health exams in a major health maintenance program in Southern California. This approach provides over 90 percent statistical power to detect genes contributing as little as three percent to blood pressure variation. The research team also scored over 60,000 genotypes at 35 gene locations involved in two major pathways regulating blood pressure, kidney or adrenergic or regulation. The genotyping was confined to the top and bottom fifth percentile participants.

Results

The researchers found significant differences in genetic contributors to blood pressure in males versus females. For example, common genetic variants of the b1-adrenergic and 2A adrenergic receptor genes contributed to blood pressure (BP) variation in females while variants at the 2 adrenergic receptor and angiotensinogen genes contributed to BP variation in males.

Conclusion

The researchers leveraged the power of using the extremes (highs and lows) of a trait (blood pressure) measured in a large community-based population with the strategy of assessing genetic variants of genes involved in two major blood pressure regulation pathways to identify gender differences in genetic contribution to blood pressure. The results reinforce previous observations of the role of gender in cardiovascular traits and imply that the development of genetic diagnostic and therapeutic indices for hypertension must take gender into account to provide an accurate assessment and treatment of hypertension.

http://www.the-aps.org

At menopause, women lose hormone protection against heart (cardiovascular) and kidney (renal) diseases, and are likely to become obese. A research team has tested the idea that estrogen deficiency in aged females may trigger the development of high blood pressure and obesity.

The results of their study, using an animal model, suggest that estrogen depletion can have these effects.

The study is entitled, "Role of Estrogens in Postmenopausal Obesity and Hypertension." It was conducted by Lourdes A. Fortepiani and Huimin Zhang, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX. The team will discuss its findings as part of the upcoming conference, Sex and Gender in Cardiovascular-Renal Physiology and Pathophysiology, being held August 9-12, 2007 at the Hyatt Regency Austin on Town Lake in Austin, TX. The event is the second scientific gathering to be sponsored by the American Physiological Society (APS; www.The-APS.org) this year.

To test their theory the researchers used 24 aged female rats. The ovaries were removed from two-thirds of the group (ovariectomized; ovx) while the ovaries of the other third of the group remained intact and served as controls. The researchers subdivided the ovx rats, giving half of the ovx group estrogen while the other half remained estrogen depleted.

Among the ovx rats, those that did not receive estrogen had significantly higher blood pressure than the control rats (126.2 versus 110.6 mmHg). The rats receiving estrogen had the lowest blood pressure levels of all (102.6 mmHg).

The researchers also noted that the rats which had their ovaries removed and did not receive estrogen compared to the intact rats:

• gained twice as much weight as the controls
• increased their leptin level by 70 percent
• increased their blood glucose level by 35 percent
• increased RAS and renal SNS by 16 and 39 percent
• experienced no change in kidney function

All the hormonal and metabolic effects were completely abolished with estrogen replacement. In other words, the rats whose ovaries were removed and received estrogen replacement did not undergo any of the changes mentioned above.

With increased life expectancy, women spend more than a third of their life in menopause. In addition, obesity is increasing dramatically in all populations and is a major cardiovascular risk factor in women after menopause. Despite the controversial data about estrogen therapy in clinical studies, the results of this study performed in aged rats suggest that the loss of estrogens after menopause may contribute to the development of obesity and hypertension, opening new therapeutic approaches to postmenopausal hypertension.

http://www.the-aps.org

The usefulness of established molecular imaging/nuclear medicine approaches in identifying the hows and whys of brain dysfunction and its potential in providing immediately useful information in treating depression are emphasized in a study in the August Journal of Nuclear Medicine.

"Individuals in a depressed emotional state have impaired cerebral (brain) blood flow," explained Omer Bonne, head of inpatient psychiatry and associate professor in the Department of Psychiatry at Hadassah-Hebrew University Medical Center in Jerusalem, Israel. "Clinical improvement in depression is accompanied by diverse changes in cerebral blood flow, according to whether patients are treated with medication or electroconvulsive treatment," he noted. "We found that antidepressant medicines normalized decreased brain blood flow usually seen in patients with depression, while electroconvulsive treatment was associated with additional decreases in blood flow," he reported. "Currently, clinical psychiatry is based almost solely on subjective observer-based judgment. Our findings suggest that objective imaging evaluations could support subjective clinical decisions," he said.

Using SPECT (single photon emission computed tomography) a molecular imaging/nuclear medicine procedure in which injected radiotracers are utilized to produce three-dimensional, computer-reconstructed images that reveal information about both structure and function"Investigators confirmed already published findings that cerebral blood flow in depressed patients is lower than in healthy control subjects, especially in frontal, limbic and subcortical brain regions. "We wanted to see whether improvement in clinical depression is accompanied by changes increases in cerebral blood flow," he said. "We found that cerebral blood flow increased only in patients whose depression improved. In contrast, cerebral blood flow remained unchanged in patients whose depressed condition persisted," detailed Bonne.

Depression is a serious and debilitating, yet treatable disease that affects every aspect of a person's health. Estimates indicate that 19 million Americans are affected by depression each year, along with their family members, friends and co-workers. Depression may be related to a chemical imbalance in the brain that makes it hard for the cells to communicate with one another. A variety of antidepressant medications and psychotherapies are used to treat depression. Sometimes electroconvulsive therapy applying an electric current briefly to produce a seizure"Is useful, especially for those whose depression is severe or life threatening or for whom repeated treatment trials with antidepressant drugs failed.

"Interestingly, patients response to two different classes of antidepressant medicines that target different neurotransmitters is associated with a similar improvement in cerebral blood flow," he noted. "However, cerebral blood flow continued to deteriorate in patients who responded to electroconvulsive therapy," added Bonne, who helped implement functional brain imaging research in psychiatry at Hadassah. Israeli researchers studied 33 depressed patients and 25 healthy control subjects with SPECT and the radiotracer 99mTc-HMPAO.

"Our findings may aid in elucidating the mechanism of depression and its treatment," said Bonne. "There may be more than one mechanism responsible for the development of depression and for mediating response to its treatment," he added. Additional research could examine whether it's possible to use functional imaging techniques to determine which patients would benefit from drug treatment and which would respond better to electroconvulsive therapy, explained Bonne. Future research should also examine the differences in brain blood flow in patients at later time points, he said.

http://www.snm.org