Trypanocidal Activity of Limonoids and Triterpenes from Cedrela fissilis

Chagas` disease is an illness that affects millions of people in Central and South America, The search for both a prophylactic drug to be added to human blood as well as a safe and reliable therapeutic drug are greatly needed to control such disease. Herein, we report the trypanocidal activity of 15 crude extracts and 14 Compounds (limonoids and triterpenes) as well as the isolation of 25 known compounds (6 limonoids, 12 triterpenes, 1 sesquiterpene, 5 steroids, and 1 flavonoid) from Cedrela fissilis. The present study shows that this plant is a Promising Source of active compounds for the control of Chagas` disease. The inhibitory activity found for odoratol indicates that it is potentially useful as an alternative for the chemoprophylactic gentian violet.

Sensitivity to cisplatin-induced mutations and elevated chromosomal aberrations in lymphocytes from sickle cell disease patients

Sickle cell disease (SCD) is an inherited disorder caused by a single nucleotide substitution in the P-globin gene. The clinical heterogeneity observed in SCD patients has been attributed to environmental and genetic factors. The patients are subjected to increased oxidative stress, particularly during vaso-occlusive crises and acute chest pain. Another possible cause of oxidative stress in SCD is the high concentration of iron in the patients` plasma. The increase in oxidative stress could be a relevant risk factor for mutagenesis and carcinogenesis. Studies on the frequency of basal chromosomal aberrations in cultured lymphocytes from SCD patients have not been reported so far. In order to contribute to the understanding of the role of the different biomarkers and their relationship with the extremely variable clinical manifestation of SCD, we investigated the frequency of chromosome damage in peripheral lymphocytes from sickle cells patients and healthy controls. We found an increased frequency of chromosome damage and percentage of aberrant metaphases in these patients when compared with control subjects, even at basal values (p < 0.05). In the cytogenetic sensitivity assay, the results showed that these patients presented a marked decrease in the mitotic index values compared with healthy controls. Cisplatin-induced chromosomal damage in lymphocytes from these patients was significantly higher than the frequency measured in healthy controls. The results obtained in the present study showed that more investigations are needed in order to elucidate the susceptibility to genomic instability of SCD patients.

Trypanocidal activity and acute toxicity assessment of triterpene acids

The present study evaluates the in vitro and in vivo trypanocidal activity of ursolic acid and oleanolic acid against the Bolivia strain of Trypanosoma cruzi. Their acute toxicity is also assessed on the basis of median lethal dose (DL50) determination and quantification of biochemical parameters. Ursolic acid is the most active compound in vitro, furnishing IC50 of 25.5 mu M and displaying 77% of trypomastigote lysis at a concentration of 128 A mu M. In agreement with in vitro assays, the results obtained for the in vivo assay reveals that ursolic acid (at a dose of 20 mg/Kg/day) provides the most significant reduction in the number of parasites at the parasitemic peak. Results concerning the LD50 assay and the biochemical parameters evaluated in the present study demonstrate that these substances can be safely used on an experimental basis.

In vitro Antitumour Activity of Orsellinates

Lichen phenolic compounds exhibit antioxidant, antimicrobial, antiproliferative. and cytotoxic activities. The purpose of this study was to evaluate the anticancer activity of lecanoric acid, a secondary metabolite of the lichen Parmotrema tinctorum, and its derivatives, orsellinates, obtained by structural modification. A cytotoxicity assay was carried out hi vitro with sulforhodamine B (SRB) using HEp-2 larynx carcinoma, MCF7 breast carcinoma, 786-0 kidney carcinoma, and B16-F10 murine melanoma cell lines, in addition to a normal (Vero) cell line in order to calculate the selectivity index of the compounds. n-Butyl orsellinate was the most active compound, with IC(50) Values (the concentration that inhibits 50% of growth) ranging from 7.2 to 14.0 mu g/ml, against all the cell lines tested. The compound was more active (IC(50), = 11.4 mu g/mL) against B16-F10 cells than was cisplatin (12.5 mu g/mL). Conversely, lecanoric acid and methyl orsellinate were less active against all cell lines, having an IC(50) value higher than 50 mu g/mL. Ethyl orsellinate was more active against HEp-2 than against MCF7, 786-0, or B16-F10 cells. The same pattern was observed for n-propyl and n-butyl orsellinates. n-Pentyl orsellinate was less active than n-propyl or n-butyl orsellinates against HEp-2 cells. The orsellinate activity increased with chain elongation (from methyl to n-butyl), a likely consequence of an increase in lipophilicity. The results revealed that the structural modification of lecanoric acid increases the cytotoxic activity of the derivatives tested.

Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy

Background: Periodontal disease shares risk factors with cardiovascular diseases and other systemic inflammatory diseases. The present study was designed to assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal disease patients and, subsequently, after periodontal therapy. Methods: We compared the plasma concentrations of MMP-2. MMP-3, MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic activity in patients with periodontal disease (n =28) with those of control subjects (n = 22) before and 3 months after non-surgical periodontal therapy. Results: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in periodontal disease patients compared with healthy controls (all P<0.05), whereas MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal disease patients compared with controls (P<0.001) and decreased after periodontal therapy (P<0.05). Conclusions: This study showed increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy. The effects of periodontal therapy suggest that it may attenuate inflammatory chronic diseases. (C) 2009 Published by Elsevier B.V.

Biotransformation using Mucor rouxii for the production of oleanolic acid derivatives and their antimicrobial activity against oral pathogens

The goal of this study is to produce oleanolic acid derivatives by biotransformation process using Mucor rouxii and evaluate their antimicrobial activity against oral pathogens. The microbial transformation was carried out in shake flasks at 30A degrees C for 216 h with shaking at 120 rpm. Three new derivatives, 7 beta-hydroxy-3-oxo-olean-12-en-28-oic acid, 7 beta,21 beta-dihydroxy-3-oxo-olean-12-en-28-oic acid, and 3 beta,7 beta,21 beta-trihydroxyolean-12-en-28-oic acid, and one know compound, 21 beta-hydroxy-3-oxo-olean-12-en-28-oic acid, were isolated, and the structures were elucidated on the basis of spectroscopic analyses. The antimicrobial activity of the substrate and its transformed products was evaluated against five oral pathogens. Among these compounds, the derivative 21 beta-hydroxy-3-oxo-olean-12-en-28-oic acid displayed the strongest activity against Porphyromonas gingivalis, which is a primary etiological agent of periodontal disease. In an attempt to improve the antimicrobial activity of the derivative 21 beta-hydroxy-3-oxo-olean-12-en-28-oic acid, its sodium salt was prepared, and the minimum inhibitory concentration against P. gingivalis was reduced by one-half. The biotransformation process using M. rouxii has potential to be applied to the production of oleanolic acid derivatives. Research and antimicrobial activity evaluation of new oleanolic acid derivatives may provide an important contribution to the discovery of new adjunct agents for treatment of dental diseases such as dental caries, gingivitis, and periodontitis.

Habitual physical activity and physical activity intensity: their relation to body composition in 5.0-10.5 year old children

Background: Concerns of a decrease in physical activity levels (PALs) of children and a concurrent increase in childhood obesity exist worldwide. The exact relation between these two parameters however has as yet to be fully defined in children. Objective: This study examined the relation in 47 children, aged 5–10.5 y (mean age 8.4plusminus0.9 y) between habitual physical activity, minutes spent in moderate, vigorous and hard intensity activity and body composition parameters. Design: Total energy expenditure (TEE) was calculated using the doubly labelled water technique and basal metabolic rate (BMR) was predicted from Schofield's equations. PAL was determined by PAL=TEE/BMR. Time spent in moderate, vigorous and hard intensity activity was determined by accelerometry, using the Tritrac-R3D. Body fatness and body mass index (BMI) were used as the two measures of body composition. Results: Body fat and BMI were significantly inversely correlated with PAL (r=-0.43, P=0.002 and r=-0.45, P=0.001). Times spent in vigorous activity and hard activity were significantly correlated to percentage body fat (r=-0.44, P=0.004 and r=-0.39, P=0.014), but not BMI. Children who were in the top tertiles for both vigorous activity and hard activity had significantly lower body fat percentages than those in the middle and lowest tertiles. Moderate intensity activity was not correlated with measures of body composition. Conclusions: As well as showing a significant relation between PAL and body composition, these data intimate that there may be a threshold of intensity of physical activity that is influential on body fatness. In light of world trends showing increasing childhood obesity, this study supports the need to further investigate the importance of physical activity for children.

Effects of interventions in health care settings on physical activity or cardiorespiratory fitness

Introduction: This paper reviews studies of physical activity interventions in health care settings to determine effects on physical activity and/or fitness and characteristics of successful interventions. Methods: Studies testing interventions to promote physical activity in health care settings for primary prevention (patients without disease) and secondary prevention (patients with cardiovascular disease [CVD]) were identified by computerized search methods and reference lists of reviews and articles. Inclusion criteria included assignment to intervention and control groups, physical activity or cardiorespiratory fitness outcome measures, and, for the secondary prevention studies, measurement 12 or more months after randomization. The number of studies with statistically significant effects was determined overall as well as for studies testing interventions with various characteristics. Results: Twelve studies of primary prevention were identified, seven of which were randomized. Three of four randomized studies with short-term measurement (4 weeks to 3 months after randomization), and two of five randomized studies with long-term measurement (6 months after randomization) achieved significant effects on physical activity. Twenty-four randomized studies of CVD secondary prevention were identified; 13 achieved significant effects on activity and/or fitness at twelve or more months. Studies with measurement at two time points showed decaying effects over time, particularly if the intervention were discontinued. Successful interventions contained multiple contacts, behavioral approaches, supervised exercise, provision of equipment, and/or continuing intervention. Many studies had methodologic problems such as low follow-up rates. Conclusion: Interventions in health care settings can increase physical activity for both primary and secondary prevention. Long-term effects are more likely with continuing intervention and multiple intervention components such as supervised exercise, provision of equipment, and behavioral approaches. Recommendations for additional research are given.

Relationships between movement initiation times and movement-related cortical potentials in Parkinson's disease

Movement-related cortical potentials recorded from the scalp reveal increasing cortical activity occurring prior to voluntary movement. Studies of set-related cortical activity recorded from single neurones within premotor and supplementary motor areas in monkeys suggest that such premovement activity may act to prime activity of appropriate motor units in readiness to move, thereby facilitating the movement response. Such a role of early stage premovement activity in movement-related cortical potentials was investigated by examining the relationship between premovement cortical activity and movement initiation or reaction times. Parkinson's disease and control subjects performed a simple button-pressing reaction time task and individual movement-related potentials were averaged for responses with short compared with long reaction times. For Parkinson's disease subjects but not for the control subjects, early stage premovement cortical activity was significantly increased in amplitude for faster reaction times, indicating that there is indeed a relationship between premovement cortical activity amplitude and movement initiation or reaction times. In support of studies of set-related cortical activity in monkeys, it is therefore suggested that early stage premovement activity reflects the priming of appropriate motor units of primary motor cortex, thereby reducing movement initiation or reaction times. (C) 1999 Elsevier Science B.V. All rights reserved.

Movement-related potentials in Parkinson's disease: External cues and attentional strategies

Hypokinetic movement can be greatly improved in Parkinson's disease patients by the provision of external cues to guide movement. It has recently been reported, however, that movement performance in parkinsonian patients can be similarly improved in the absence of external cues by using attentional strategies, whereby patients are instructed to consciously attend to particular aspects of the movement which would normally be controlled automatically. To study the neurophysiological basis of such improvements in performance associated with the use of attentional strategies, movement-related cortical potentials were examined in Parkinson's disease and control subjects using a reaction time paradigm. One group of subjects were explicitly instructed to concentrate on internally timed responses to anticipate the presentation of a predictably timed go signal. Other subjects were given no such instruction regarding attentional strategies. Early-stage premovement activity of movement-related potentials was significantly increased in amplitude and reaction times were significantly faster for Parkinson's disease subjects when instructed to direct their attention toward internally generating responses rather than relying on external cues. It is therefore suggested that the use of attentional strategies may allow movement to be mediated by less automatic and more conscious attentional motor control processes which may be less impaired by basal ganglia dysfunction, and thereby improve movement performance in Parkinson's disease.

El Nino and arboviral disease prediction

Recent El Nino events have stimulated interest in the development of modeling techniques to forecast extremes of climate and related health events. Previous studies have documented associations between specific climate variables (particularly temperature and rainfall) and outbreaks of arboviral disease. In some countries, such diseases are sensitive to Fl Nino. Here we describe a climate-based model for the prediction of Ross River virus epidemics in Australia. From a literature search and data on case notifications, we determined in which years there were epidemics of Ross River virus in southern Australia between 1928 and 1998. Predictor variables were monthly Southern Oscillation index values for the year of an epidemic or lagged by 1 year. We found that in southeastern states, epidemic years were well predicted by monthly Southern Oscillation index values in January and September in the previous year. The model forecasts that there is a high probability of epidemic Ross River virus in the southern states of Australia in 1999. We conclude that epidemics of arboviral disease can, at least in principle, be predicted on the basis of climate relationships.

Between-year fluctuations in schizophrenia birth rate and associations with the Southern Oscillation Index, cloud cover and sunshine

Our group have recently proposed that low prenatal vitamin D may be a risk-modifying factor for schizophrenia. Climate variability impacts on vitamin D levels in a population via fluctuations in the amount of available UV radiation. In order to explore this hypothesis, we examined fluctuations in the birthrates for people with schizophrenia born between 1920 and 1967 and three sets of variables strongly associated with UV radiation. These included: (a) the Southern Oscillation Index (SOI), a marker of El Nino which is the most prominent meteorological factor that influences Queensland weather: (b) measures of cloud cover and (c) measures of sunshine. Schizophrenia births were extracted from the Queensland Mental Health register and corrected for background population birth rates. Schizophrenia birth rates had several apparently non-random features in common with the SO1. The prominent SO1 fluctuation event that occurred between 1937 and 1943 is congruent with the most prominent fluctuation in schizophrenia birth rates. The relatively flat profile of SOI activity between 1927 and 1936 also corresponds to the flattest period in the schizophrenia time series. Both time series have prominent oscillations in the 3 ~, year range between 1946 and 1960. Significant associations between schizophrenia birth rates and measures of both sunshine and cloud cover were identified,and all three time series shared periodicity in the 3-4 year range. The analyses suggest that the risk of schizophrenia is higher for those born during times of increased cloud cover,reduced sunshine and positive SO1. These ecological analyses provide initial support for the vitamin D hypothesis, however alternative non-genetic candidate exposures also need to be considered. Other sites with year-to-year fluctuations in cloud cover and sunshine should examine patterns of association between these climate variables and schizophrenia birth rates. The Stanley Foundation supported this project.

Death and readmission in the year after hospital admission with cardiovascular disease: the Hunter Area Heart and Stroke Register

Objectives: To compare outcomes one year after hospital admission for patients initially discharged with a diagnosis of acute myocardial infarction (AMI), other ischaemic heart disease (other IHD), congestive heart failure (CHF) or stroke. Design: Cohort study. Setting: Hunter Area Heart and Stroke Register, which registers all patients admitted with heart disease or stroke to any of the 22 hospitals in the Hunter Area Health Service in New South Wales. Patients: 4981 patients with AMI, other IHD, CHF or stroke admitted to hospital as an emergency between 1 July 1995 and 30 June 1997 and followed for at least one year. Main outcome measures: Death from any cause or emergency hospital readmission for cardiovascular disease. Results: In-hospital mortality varied from 1% of those with other IHD to 22% of those with stroke. Almost a third of all patients discharged alive (and 38% of those aged 70 or more) had died or been readmitted within one year. This varied from 22% of those with stroke to 49% of those with CHF. The causes of death and readmission were from a spectrum of cardiovascular disease, regardless of the cause of the original hospital admission. Conclusions: Data from this population register show the poor outcome, especially with increasing age, among patients admitted to hospital with cardiovascular disease. This should alert us to determine whether optimal secondary prevention strategies are being adopted among such patients.

Social-cognitive and perceived environment influences associated with physical activity in older Australians

Background, Regular physical activity in older adults can facilitate healthy aging, improve functional capacity, and prevent disease. However, factors associated with physical inactivity in older populations are poorly understood. This study attempts to identify social-cognitive and perceived environmental influences associated with physical activity participation in older populations. Methods. In a randomly selected sample of 449 Australian adults age 60 and older, we assessed self-reported physical activity and a range of social-cognitive and perceived environmental factors. Respondents were classified as sufficiently active and inactive based on energy expenditure estimates (kcal/week) derived from self-reported physical activity. Two logistic regression models, with and without self-efficacy included, were conducted to identify modifiable independent predictors of physical activity. Results. Significantly more males than females were physically active. Physical activity participation was related to age with a greater proportion of those age 65-69 being active than those age 60-64 or 70 or older. High self-efficacy, regular participation of friends and family, finding footpaths safe for walking, and access to local facilities were significantly associated with being active. Conclusion. Identifying predictors of physical activity in older populations, particularly social support, facility access, and neighbourhood safety, can inform the development of policy and intervention strategies to promote the health of older people. (C) 2000 American Health Foundation and Academic Press.