naturopathydigest.com -- Critical Research

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Critical Research

Critical Research is a regular feature in Naturopathy Digest. Each month, we provide abstracts from studies published in the top peer-reviewed journals; each abstract includes the complete citation and an online link to the journal. Whenever possible, this link directs you to a page where you can order the full text of the study, if desired.

This Month's Featured Abstract

A nationwide [Spain] study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use.

Lanas A, Perez-Aisa MA, Feu F, et al.

Background: The worst outcome of gastrointestinal complications is death. Data regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or aspirin use are scarce.
Aim: To determine mortality associated with hospital admission due to major gastrointestinal (GI) events and NSAID/aspirin use.
Methods: The study was based on actual count of deaths from two different data sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198 people. Study 2 used a database from 197 general hospitals, representative of the 269 hospitals in the Spanish National Health System. Information regarding gastrointestinal complications and deaths was obtained throughout the Minimum Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed to NSAID/aspirin use were estimated on the basis of prospectively collected data from hospitals of study 1.
Results: The incidence of hospital admission due to major GI events of the entire (upper and lower) gastrointestinal tract was 121.9 events/100,000 persons/year, but those related to the upper GI tract were six times more frequent. Mortality rate was 5.57% (95% CI = 4.9-6.7), and 5.62% (95% CI = 4.8-6.8) in study 1 and study 2, respectively. Death rate attributed to NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively, or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin deaths can be attributed to low-dose aspirin use.
Conclusion: Mortality rates associated with either major upper or lower GI events are similar but upper GI events were more frequent. Deaths attributed to NSAID/ASA use were high but previous reports may have provided an overestimate and one-third of them can be due to low-dose aspirin use.
Source: Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. American Journal of Gastroenterology 2005;100:1685-93.

Iron absorption from soybean ferritin in nonanemic women.

Lönnerdal B, Bryant A, Xiaofeng L, Theil EC

Background: Dietary ferritin, a protein cage around an iron mineral, is an underestimated source of bioavailable iron. Plant ferritin, the most common dietary ferritin, has not been studied. Iron from animal ferritin is absorbed as well as is iron from FeSO₄ in women.
Objective: The objective was to examine iron absorption from purified soybean ferritin.
Design: Healthy, nonanemic women (n = 16) were fed a standardized meal (bagel, cream cheese, and apple juice) containing 1 µCi ⁵⁹Fe/meal as FeSO₄ or (extrinsically labeled) as iron-free soybean ferritin reconstituted with the high phosphate characteristic of plant ferritin (iron:phosphorus = 4:1). Iron-free, apo-soybean ferritin was prepared (with the use of thioglycolic acid and extensive dialysis) from purified ferritin. In a randomized crossover design, the other labeled meal, which contained FeSO₄ or ferritin, was given after 4 weeks. The subjects received 140 µg Fe as ferritin (2.5 mg) or as FeSO₄. After 28 days, whole-body ⁵⁹Fe and ⁵⁹Fe in red blood cells were measured before and after dosing.
Results: There was no significant difference in whole-body iron absorption from soybean ferritin (29.9 19.8%) and that from FeSO₄ (34.3 23.6%) or in iron absorption calculated from red blood cell incorporation (33.0 20.1% for soybean ferritin and 35.3 23.4% for FeSO₄), which confirmed previous results with animal ferritin that was mineralized and labeled similarly. An inverse relation was observed between serum ferritin and iron absorption from both ferritin and FeSO4, which suggested that sensors regulating iron absorption respond similarly to iron provided as ferrous salts or as ferritin mineral.
Conclusion: Iron from soybean ferritin is well-absorbed and may provide a model for novel, utilizable, plant-based forms of iron for populations with a low iron status.
Source: American Journal of Clinical Nutrition, January 2006;83(1):103-107.

Three-month treatment of reactive arthritis with azithromycin: a EULAR double-blind, placebo-controlled study.

Kvien TK, Gaston JS, Bardin T, et al.

Objective: To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis (ReA).
Methods: 186 patients from 12 countries were enrolled in a randomised, double-blind, placebo- controlled trial. Inclusion criteria were inflammatory arthritis of < or =6 swollen joints, and disease duration of < or =2 months. All patients received a single azithromycin dose (1 g) as conventional treatment for possible Chlamydia infection, and were then randomly allocated to receive weekly azithromycin or placebo. Clinical assessments were made at 4-week intervals for 24 weeks.
Results: 152 patients were analysable (34 failed entry criteria), with a mean (SD) age of 33.8 (9.4) and duration of symptoms 30.7 (17.5) days. Mean C reactive protein (CRP) was 48 mg/l, and approximately 50% of those typed were HLA-B27+, suggesting that the inclusion criteria successfully recruited patients with acute ReA. Treatment and placebo groups were well matched for baseline characteristics. There were no statistical differences for changes in any end point (swollen and tender joint count, joint pain, back pain, heel pain, physician and patient global assessments, and CRP) between the active treatment and placebo groups, analysed on an intention-to-treat basis or according to protocol completion. The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different. Adverse events were generally mild, but were more commonly reported in the azithromycin group.
Conclusions: This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in ReA.
Source: Annals of the Rheumatic Diseases, September 2004;63(9):1113-9.

Poststreptococcal reactive arthritis: what is it and how do we know?

Mackie SL, Keat A. Dept. of Rheumatology, Northwick Park Hospital, Harrow, Middlesex, U.K.

Objective: To find out whether poststreptococcal reactive arthritis (PSRA) is a discrete, homogeneous clinical syndrome.
Method: Literature review from case reports and case series.
Results: One hundred and eighty-eight cases were identified. The age distribution was bimodal, with one peak in childhood and one peak in adulthood. Eighty-three percent of streptococcal isolates were group A. The clinical presentation was heterogeneous but appeared different both from that of acute rheumatic fever (ARF) and from that of HLA B27-associated reactive arthritis. Carditis was rare.
Conclusions: The term PSRA encompasses significant heterogeneity. The link between the arthritis and the streptococcal infection is unproven.
Source: Rheumatology (Oxford), August 2004;43(8):949-54.

Alpha-lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation.

Wenzel U, Nickel A, Daniel H

The antioxidant alpha-lipoic acid (ALA) has been shown to affect a variety of biological processes associated with oxidative stress, including cancer. We determined in HT-29 human colon cancer cells whether ALA is able to affect apoptosis as an important parameter disregulated in tumour development. Exposure of cells to ALA or its reduced form, dihydrolipoic acid (DHLA), for 24-hour dose dependently increased caspase-3-like activity and was associated with DNA fragmentation. DHLA but not ALA was able to scavenge cytosolic O2-* in HT-29 cells, whereas both compounds increased O2-*-generation inside mitochondria. Increased mitochondrial O2-*-production was preceded by an increased influx of lactate or pyruvate into mitochondria and resulted in the down-regulation of the anti-apoptotic protein bcl-X(L).
Mitochondrial O2-*-generation and apoptosis induced by ALA and DHLA could be prevented by the O2-*-scavenger benzoquinone. Moreover, when the lactate/pyruvate transporter was inhibited by 5-nitro-2-(3-phenylpropylamino) benzoate, ALA- and DHLA-induced mitochondrial ROS-production and apoptosis were blocked. In contrast to HT-29 cells, no apoptosis was observed in non-transformed human colonocytes in response to ALA or DHLA addition. In conclusion, our study provides evidence that ALA and DHLA can effectively induce apoptosis in human colon cancer cells by a pro-oxidant mechanism that is initiated by an increased uptake of oxidizable substrates into mitochondria.
Source: Apoptosis March 2005;10(2):359-68. (access journal by clicking on "Browse Publications A-Z.")

Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors.

Goodarz D, Vander Hoorn S, Lopez A, et al. The Comparative Risk Assessment Collaborating Group (Cancers)

Introduction: With respect to reducing mortality, advances in cancer treatment have not been as effective as those for other chronic diseases; effective screening methods are available for only a few cancers. Primary prevention through lifestyle and environmental interventions remains the main way to reduce the burden of cancers. In this report, we estimate mortality from 12 types of cancer attributable to nine risk factors in seven World Bank regions for 2001.
Methods: We analysed data from the Comparative Risk Assessment project and from new sources to assess exposure to risk factors and relative risk by age, sex, and region. We applied population attributable fractions for individual and multiple risk factors to site-specific cancer mortality from WHO.
Findings: Of the 7 million deaths from cancer worldwide in 2001, an estimated 2.43 million (35%) were attributable to nine potentially modifiable risk factors. Of these, 0.76 million deaths were in high-income countries and 1.67 million in low-and-middle-income nations. Among low-and-middle-income regions, Europe and Central Asia had the highest proportion (39%) of deaths from cancer attributable to the risk factors studied. 1.6 million of the deaths attributable to these risk factors were in men and 0.83 million in women. Smoking, alcohol use, and low fruit and vegetable intake were the leading risk factors for death from cancer worldwide and in low- and middle-income countries. In high-income countries, smoking, alcohol use, and overweight and obesity were the most important causes of cancer. Sexual transmission of human papilloma virus is a leading risk factor for cervical cancer in women in low- and middle-income countries.
Interpretation: Reduction of exposure to key behavioural and environmental risk factors would prevent a substantial proportion of deaths from cancer.
Source: The Lancet 2005;366:1784-1793.

Hepatitis C virus seroprevalence and genotypes in patients with diffuse connective tissue diseases and spondyloarthropathies.

Barbosa VS, Silva NA, Martins RM

Many extrahepatic manifestations, including rheumatic diseases, have been reported to be associated with hepatitis C virus (HCV) infection. In order to investigate the prevalence of HCV infection among patients with rheumatic diseases, in the present study we interviewed 367 patients and tested their blood samples for HCV antibodies (anti-HCV) by an enzyme-linked immunosorbent assay. Anti-HCV-reactive samples were retested for confirmation by a line immunoassay and also for HCV RNA detection by the polymerase chain reaction. HCV RNA-positive samples were genotyped by INNO-LIPA. An overall HCV infection prevalence of 1.9% (7/367) was found. Of the 7 HCV-infected patients, 4 had systemic lupus erythematosus and 3 rheumatoid arthritis, resulting in positivity rates of 2.3 and 3.4%, respectively. HCV RNA genotyping revealed the presence of subtypes 1a (57.1%), 1b (28.6%) and 3a (14.3%). The clinical course was favorable for all HCV-infected patients, except one, who died due to renal insufficiency related to lupus nephritis. These results demonstrate a low HCV infection prevalence among the population studied. In the few positive cases, we observed no adverse influence of this infection on the clinical evolution of the rheumatic disease.
Source: Braz J Med Biol Research, May 2005;38(5):801-5.

High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis.

Li SY, Liu Y, Sigmon VK, et al.

High-fat diet intake often leads to obesity, insulin resistance and hypertension, which present a common and detrimental health problem. However, precise mechanism underlying tissue damage due to high-fat diet-induced obesity has not been carefully elucidated. The present study was designed to examine the effect of high-fat diet intake on visceral advanced glycation end products (AGEs) formation, nuclear O-Glc-NAc modification and apoptosis in heart, liver and kidney. Adult male Sprague-Dawley weight-matched rats were fed for 12 weeks with a high-fat diet (45% kcal from fat) or an isocaloric low-fat diet (10% kcal from fat). High-fat diet feeding significantly elevated body weight. Blood pressure and heart rate were comparable between the two rat groups. Competitive enzyme-linked immunosorbent assay showed significantly elevated serum AGE levels, visceral AGE formation, caspase-3 activation and cytoplasmic DNA fragmentation in heart and liver but not kidney samples of high-fat diet fed rats compared with those from low-fat diet fed group. Western blot analysis further revealed that high-fat diet feeding induced overt nuclear O-Glc-NAc modification and p38 mitogen-activated protein kinase activation in heart and liver although not in kidney samples of the high-fat diet-fed rats. Collectively, our results indicated that high-fat diet intake is associated with obesity accompanied by elevated serum and visceral AGEs, visceral post-translational nuclear O-Glc-NAcylated modification and apoptosis, which may contribute to high-fat diet-induced tissue damage.
Source: Diabetes Obes Metab, July 2005;7(4):448-54.