'As soon as they can hold a glass, they begin taking alcohol': a qualitative study on early childhood substance use in Mbale District, Uganda.

BACKGROUND: Globally, substance use is a leading contributor to the burden of disease among young people, with far reaching social, economic and health effects. Following a finding of harmful alcohol use among 5-8-year-old children in Mbale District, Uganda, this study aims to investigate community members' views on early childhood substance use among children below the age of 10 years. METHODS: In 2016, we conducted eight focus group discussions with 48 parents and 26 key informant interviews with teachers, health workers, alcohol distributors, traditional healers, religious leaders, community leaders and youth workers. We used thematic content analysis. Four participants and two research assistants reviewed and confirmed the findings. RESULTS: Alcohol in everyday life: 'Even children on laps taste alcohol': Almost all participants confirmed the existence of and concern for substance use before age 10. They described a context where substance use was widespread in the community, especially intake of local alcoholic brews. Children would access substances in the home or buy it themselves. Those living in poor neighbourhoods or slums and children of brewers were described as particularly exposed. Using substances to cope: 'We don't want them to drink': Participants explained that some used substances to cope with a lack of food and resources for childcare, as well as traumatic experiences. This made children in deprived families and street-connected children especially vulnerable to substance use. Participants believed this was a result of seeing no alternative solution. CONCLUSIONS: To our knowledge, this is the first study to describe the context and conditions of childhood substance use before age 10 in Mbale District, Uganda. The study shows that community members attributed early childhood substance use to a social context of widespread use in the community, which was exacerbated by conditions of material and emotional deprivation. These social determinants for this practice deserve public health attention and intervention.

'There is nowhere to take the child': a qualitative study of community members' views on managing early childhood substance use in Mbale, Uganda.

BACKGROUND: Harmful alcohol use by 5-8-year-old children has been identified in Mbale District, Uganda. To further examine this finding, the present study explores the experiences and perceptions of community members regarding how childhood substance use (before age 10) is managed in this area. METHODS: We conducted eight focus group discussions with 48 parents of children aged < 10 years and 26 key informant interviews with teachers, health workers, child protection workers, police, local stakeholders, brewers, and others. Thematic content analysis was performed. RESULTS: Three main themes were identified: 'We don't talk about it': Despite concern, childhood substance use was not addressed in the community. Participants attributed this to three main factors related to a lack of leadership in addressing it, changing acceptability for peer parental interference, and uncertainty about repercussions related to children's rights. 'There is nowhere to take the child': Schools, police, and remand homes were intuitively considered appropriate arenas for managing childhood substance use but were considered inaccessible, unresponsive, and inadequate due to insufficient resources, competence, and training. Since substance use was not considered a medical problem, help from the health sector was only sought for adverse consequences, such as injury. This left the participants with the experience that there was in effect nowhere to take the child. 'The government has not done so much': The participants called for government action and clear laws that would regulate the availability of alcohol and other substances to children, but they had limited trust in the capacity and commitment of the government to act. CONCLUSIONS: The participants were concerned about childhood alcohol and substance use, but the complexity and magnitude of the problem left them feeling incapacitated in responding. Relevant factors were identified on the community, institutional, and the government level, such as a lack of leadership in addressing it, a loss of mandate to interfere in child-rearing, inadequate services, weak legal structures, and missing government action. A strengthening of collective agency and public policy is necessary to prevent and address childhood alcohol and substance use.

The impact of blackcurrant juice on attention, mood and brain wave spectral activity in young healthy volunteers.

There is a growing body of evidence from randomized controlled trials which indicates that consumption of berries has a positive effect upon the cognitive function of healthy adults. It has been recommended that studies combining cognitive and physiological measures be undertaken in order to strengthen the evidence base for the putative effects of flavonoid consumption on cognitive outcomes. This pilot study utilized a randomized, double-blind and placebo controlled crossover design to assess the influence of the acute administration of anthocyanin-rich blackcurrant juice, standardized at 500 mg of polyphenols, on mood and attention. Additionally, this trial used electroencephalography (EEG) to assess if any changes in cognitive performance are associated with changes in localized prefrontal cortex neuronal activity in nine healthy young adults. Outcomes from the pilot EEG data highlight an anxiolytic effect of the consumption of a single serve blackcurrant juice, as indexed by a suppression of α spectral power, and an increase in the slow wave δ and θ spectral powers. There was also an indication of greater alertness and lower fatigue, as indexed by an increase in ß power and suppression of α spectral power. Outcomes from the CogTrack™ system indicated a small acute increase in reaction times during the digit vigilance task.

In vitro protective effects of an aqueous extract of Clitoria ternatea L. flower against hydrogen peroxide-induced cytotoxicity and UV-induced mtDNA damage in human keratinocytes.

The traditional practice of eating the flowers of Clitoria ternatea L. or drinking their infusion as herbal tea in some of the Asian countries is believed to promote a younger skin complexion and defend against skin aging. This study was conducted to investigate the protective effect of C. ternatea flower water extract (CTW) against hydrogen peroxide-induced cytotoxicity and ultraviolet (UV)-induced mitochondrial DNA (mtDNA) damage in human keratinocytes. The protective effect against hydrogen peroxide-induced cytotoxicity was determined by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and mtDNA damage induced by UV was determined by polymerase chain reaction. Preincubation of HaCaT with 100, 250, and 500 µg/ml CTW reduced cytotoxicity effects of H2 O2 compared with control (H2 O2 alone). CTW also significantly reduced mtDNA damage in UV-exposed HaCaT (p < .05). CTW was chemically-characterized using high resolution liquid chromatography-mass spectrometry. The main compounds detected were assigned as anthocyanins derived from delphinidin, including polyacylated ternatins, and flavonol glycosides derived from quercetin and kaempferol. These results demonstrated the protective effects of C. ternatea flower extracts that contain polyacylated anthocyanins and flavonol glycosides as major constituents, against H2 O2 and UV-induced oxidative stress on skin cells, and may provide some explanation for the putative traditional and cosmetic uses of C. ternatea flower against skin aging.

Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults.

PURPOSE: Berry-derived phenolic compounds found in grapes have been associated with a number of health benefits, including the augmentation of human brain function and cognition. Previous intervention studies of Concord grape juice have demonstrated improvement to memory and driving ability following 3- to 4-month supplementation in middle-aged and older adults. However, no studies to date have demonstrated acute cognitive benefits of grape juice, and investigation of these effects in young adults is lacking. METHODS: This randomised, placebo-controlled, double-blind, counterbalanced-crossover study, assessed the effects of 230 ml purple grape juice or sugar-matched control in 20 healthy young adults. Computerised measures of episodic memory, working memory, attention and mood were completed at baseline and following a 20-min absorption period. RESULTS: Purple grape juice significantly improved reaction time on a composite attention measure (p = 0.047) and increased calm ratings (p = 0.046) when compared to placebo. Order effects also indicated an enduring positive effect on pre-dose memory reaction time (p = 0.018) and post-dose calm ratings (p = 0.019) when purple grape was consumed first. CONCLUSIONS: These findings in a small sample of healthy young adults suggest that purple grape juice can acutely enhance aspects of cognition and mood. No significant effects of juice were observed on memory measures, suggesting that these may be less susceptible to manipulation following acute supplementation in healthy young adults. Potential mechanisms underlying these effects include modulation of cerebral blood flow, glucoregulation and inhibition of monoamine oxidase activity, all of which require further exploration.

Erratum to: Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults.

In the original publication of the article, on page 7, paragraph "Discussion", line 12, 'blackcurrant has been observed to increase digit vigilance reaction time' should read as 'blackcurrant has been observed to decrease digit vigilance reaction time'.

Barriers to biomedical care and use of traditional medicines for treatment of cervical cancer: an exploratory qualitative study in northern Uganda.

Use of traditional medicines for treatment of cancers has increased worldwide. We used a qualitative approach to explore barriers to biomedical care and reasons for use of traditional medicines for the treatment of cervical cancer in Gulu, northern Uganda. We carried out 24 focus group discussions involving men and women aged 18-59 years. We employed content analyses technique in data analysis. Traditional medicines were used mainly due to barriers to biomedical care for cervical cancer. The barriers included health system factors, for example long distances to health facilities and unavailability of medicines; health workers' factors, for example negative attitudes towards patients and demands for bribes; individual patient's factors, for example inability to pay for medical care; and socio-cultural beliefs about superiority of traditional medicines and perceived greater privacy in accessing traditional healers. Barriers to biomedical care and community beliefs in the effectiveness of traditional medicines encourage use of traditional medicines for treatment of cervical cancer but might hinder help-seeking at biomedical facilities. There is need for targeted culturally sensitive awareness campaign to promote effectiveness of modern medicine and to encourage cautious use of traditional medicines in the treatment of cervical cancer.

Effects of five Ayurvedic herbs on locomotor behaviour in a Drosophila melanogaster Parkinson's disease model.

Current conventional treatments for Parkinson's disease (PD) are aimed at symptom management, as there is currently no known cure or treatment that can slow down its progression. Ayurveda, the ancient medical system of India, uses a combination of herbs to combat the disease. Herbs commonly used for this purpose are Zandopa (containing Mucuna pruriens), Withania somnifera, Centella asiatica, Sida cordifolia and Bacopa monnieri. In this study, these herbs were tested for their potential ability to improve climbing ability of a fruit fly (Drosophila melanogaster) PD model based on loss of function of phosphatase and tensin-induced putative kinase 1 (PINK1). Fruit flies were cultured on food containing individual herbs or herbal formulations, a combination of all five herbs, levodopa (positive control) or no treatment (negative control). Tests were performed in both PINK1 mutant flies and healthy wild-type (WT) flies. A significant improvement in climbing ability was observed in flies treated with B. monnieri compared with untreated PINK1 mutant flies. However, a significant decrease in climbing ability was observed in WT flies for the same herb. Centella asiatica also significantly decreased climbing ability in WT flies. No significant effects were observed with any of the other herbs in either PINK1 or WT flies compared with untreated flies.

Environmental interactions with the toxicity of plant essential oils to the poultry red mite Dermanyssus gallinae.

The toxicity of a range of plant essential oils to the poultry red mite, Dermanyssus gallinae (De Geer) (Acari: Dermanyssidae), a serious ectoparasitic pest of laying hens throughout Europe and elsewhere, was assessed in the laboratory. Dermanyssus gallinae may cause losses in egg production, anaemia and, in extreme cases, death of hens. With changes in legislation and consumer demand, alternatives to synthetic acaricides are needed to manage this pest. Fifty plant essential oils were selected for their toxicity to arthropods reported in the literature. Twenty-four of these essential oils were found to kill > 75% of adult D. gallinae in contact toxicity tests over a 24-h period at a rate of 0.21 mg/cm(2). Subsequent testing at lower rates showed that the essential oils of cade, manuka and thyme were especially toxic to adult D. gallinae. The toxicity of the seven most acaricidal essential oils was found to be stable at different temperatures likely to be encountered in commercial poultry housing (15 degrees C, 22 degrees C and 29 degrees C), although results suggest that humidity and dust might influence the toxicity of some of the oils tested. The toxicity of clove bud essential oil to D. gallinae, for example, was increased at high humidity and dust levels compared with ambient levels. The results suggest that certain essential oils may make effective botanical pesticides for use against D. gallinae, although it is likely that issues relating to the consistency of the toxic effect of some oils will determine which oils will be most effective in practice.

Toxicity of plant essential oils to different life stages of the poultry red mite, Dermanyssus gallinae, and non-target invertebrates.

Seven essential oils with potential as acaricides for use against the poultry red mite, Dermanyssus gallinae (De Geer) (Acari: Dermanyssidae), were selected for study. These products (essential oils of manuka, cade, pennyroyal, thyme, garlic, clove bud and cinnamon bark) were deployed against different life stages of D. gallinae in laboratory tests at the (lethal concentration) LC(50) level for adult mites. For all essential oils tested, toxicity to D. gallinae juveniles was as high as toxicity to adults, if not higher. However, at the LC(50) level determined for adults, some oils were ineffective in preventing hatching of D. gallinae eggs. The essential oils were also tested under laboratory conditions at their LC(90) levels for D. gallinae adults on two model non-target species, the brine shrimp, Artemia salina (L.), and the mealworm beetle, Tenebrio molitor (L.). Results showed that not all essential oils were as toxic to A. salina and T. molitor as they were to D. gallinae, suggesting that it may be possible to select certain oils for development as acaricides against D. gallinae that would have minimal impact on non-target organisms. However, the level of toxicity to A. salina and T. molitor was not consistent across the selected essential oils.

In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and ß-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells.

Withania somnifera L. Dunal (Solanaceae), also known as 'ashwagandha' in Sanskrit and as 'Indian ginseng', is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer, with antiaging, antistress, immunomodulatory and antioxidant properties. There is a paucity of data on the potential neuroprotective effects of W. somnifera root, as traditionally used, against H(2)O(2)- and Aß((1-42))-induced cytotoxicity which are current targets for novel approaches to treat dementia, especially dementia of the Alzheimer's type (AD). In this study, an aqueous extract prepared from the dried roots of W. somnifera was assessed for potential protective effects against H(2)O(2)- and Aß((1-42))-aggregated fibril cytotoxicity by an MTT assay using a differentiated rat pheochromocytoma PC12 cell line. The results suggest that pretreatments of differentiated PC12 cells with aqueous extracts of W. somnifera root significantly protect differentiated PC12 cells against both H(2)O(2)- and Aß((1-42))-induced cytotoxicity, in a concentration dependent manner. To investigate the compounds that could explain the observed effects, the W. somnifera extract was analysed by liquid chromatography-serial mass spectrometry and numerous withanolide derivatives, including withaferin A, were detected. These results demonstrate the neuroprotective properties of an aqueous extract of W. somnifera root and may provide some explanation for the putative ethnopharmacological uses of W. somnifera for cognitive and other neurodegenerative disorders that are associated with oxidative stress.

Repellence of plant essential oils to Dermanyssus gallinae and toxicity to the non-target invertebrate Tenebrio molitor.

With changes in legislation and consumer demand, alternatives to synthetic acaricides to manage the poultry red mite Dermanyssus gallinae (De Geer) in laying hen flocks are increasingly needed. These mites may cause losses in egg production, anaemia and even death of hens. It may be possible to use plant-derived products as D. gallinae repellents, especially if such products have a minimal impact on non-target organisms. An experiment was conducted with D. gallinae to assess the repellence of a range of plant essential oils, previously found to be of varying toxicity (relatively highly toxic to non-toxic) to this pest. Experiments were also undertaken to assess the toxicity of these products to mealworm beetles (Tenebrio molitor L.), a non-target invertebrate typical of poultry production systems. Results showed that all seven essential oils tested (manuka, thyme, palmarosa, caraway, spearmint, black pepper and juniper leaf) were repellent to D. gallinae at 0.14mg oil/cm(3) (initial concentration) during the first 2 days of study. Thyme essential oil appeared to be the most effective, where repellence lasted until the end of the study period (13 days). At the same concentration toxicity to T. molitor differed, with essential oils of palmarosa and manuka being no more toxic to adult beetles than the control. There was neither a significant association between the rank toxicity and repellence of oils to D. gallinae, nor the toxicity of oils to D. gallinae (as previously determined) and T. molitor.

Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY).

BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LIMCs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. AIM: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. RESULTS: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and more frequent INR monitoring and contraceptive counselling. CONCLUSION: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers' knowledge and efficiency in caring for RHD patients.

Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil.

In vitro anticholinesterase activities of eight commercially available terpenoid constituents of Salvia lavandulaefolia have been investigated. These included 1,8-cineole, camphor, alpha-pinene, beta-pinene, borneol, caryophyllene oxide, linalool and bornyl acetate. Dose-dependent inhibition of acetylcholinesterase (AChE) by these chemical constituents was determined using the method of Ellman [Biochem. Pharmacol. 7 (1961) 88]. The IC50 value of 1,8-cineole was 0.06+/-0.01 mg/ml similar to that of the essential oil (0.05+/-0.01 mg/ml). Analyses of the expected inhibitions based on the prediction of a zero interactive response of a combination at its naturally occurring ratios were carried out in comparison with observed inhibition. Minor synergy was apparent in 1,8-cineole/alpha-pinene and 1,8-cineole/caryophyllene oxide combinations, with interaction indexes not exceeding 0.5. In contrast, a combination of camphor and 1,8-cineole was antagonistic with an interaction index of 2. A combination of all eight compounds was zero interactive. A combination of six constituents, excluding 1,8-cineole and camphor, was used to compare the method of expected response of a combination with a method of summation. These findings reveal that the inhibitory activity of the oil results from a complex interaction between its constituents, which produce both synergistic and antagonistic responses between the component terpenes. Understanding such interactions is important in comparing species on the basis of chemical composition.

Bioindicators of enhanced nitrogen deposition.

Increased deposition of atmospheric N largely from intensive agriculture is affecting biodiversity and the composition of natural and semi-natural vegetation in Europe. The value of species based bioindicators such as the Ellenberg N index and measurements of total tissue N and free amino acids in key plant species, is described with reference to a mixed woodland downwind of a livestock farm in the Scottish Borders, operated for over 20 years with a measured spatial gradient of ammonia concentration (29-1.5 microg m(-3)). All the indicators examined showed a relationship with N deposition and provided some indication of vegetation change. Total tissue N and arginine concentrations were most closely linked with ammonia concentrations and N deposition, with r(2) values of >0.97 and >0.78 respectively.

Effect of brief training on reliability and applicability of Global Assessment of functioning scale by Psychiatric clinical officers in Uganda.

BACKGROUND: The Global Assessment of Functioning (GAF) is the standard method and an essential tool for representing a clinician's judgment of a patient's overall level of psychological, social and occupational functioning. As such, it is probably the single most widely used method for assessing impairment among the patients with psychiatric illnesses. OBJECTIVE: To assess the effects of one-hour training on application of the GAF by Psychiatric Clinical Officers' in a Ugandan setting. METHOD: Five Psychiatrists and five Psychiatric Clinical Officers (PCOs) or Assistant Medical Officers who hold a 2 year diploma in Clinical Psychiatry were randomly selected to independently rate a video-recorded psychiatric interview according to the DSM IV-TR. The PCOs were then offered a one-hour training on how to rate the GAF scale and asked to rate the video case interview again. All ratings were assigned on the basis of past one year, at admission and current functioning. Interclass correlations (ICC) were computed using two-way mixed models. RESULTS: The ICC between the psychiatrists and the PCOs before training in the past one year, at admission and current functioning were +0.48, +0.51 and +0.59 respectively. After training, the ICC coefficients were +0.60, +0.82 and +0.83. CONCLUSION: Brief training given to PCOs improved the applications of their ratings of GAF scale to acceptable levels. There is need for formal training to this cadre of psychiatric practitioners in the use of the GAF.

The role of psycho-education in improving outcome at a general hospital psychiatry clinic in Uganda.

OBJECTIVE: While psychoeducation has been shown to positively affect outcomes in psychiatric disorders, its utility has been little studied in developing countries. The current study sought to examine the role of psychoeducation at a general psychiatric outpatient clinic in Kampala, Uganda in improving clinic attendance, treatment adherence, and clinical outcomes. METHOD: A prospective case-control study using a quasi-experimental design was conducted in 117 patients suffering various psychiatric disorders. Participants were recruited for two months and then followed for a further three months after recruitment ended. Participants in the intervention group received formalized psychoeducation sessions at each clinic visit in addition to the usual psychiatric evaluation and care. Participants in the control group received the usual clinical care. Measured outcomes were knowledge of mental illness, compliance with medications and follow-up, and Clinical Global Impression (CGI). RESULTS: The groups did not differ with respect to sociodemographic characteristics or attendance at scheduled follow-up visits. Both groups significantly improved on the CGI, but with no significant difference between the groups. However, the intervention group was more likely to adhere to medication, and their knowledge of mental illness was significantly higher at follow-up. CONCLUSION: These data suggest that psychoeducation is a beneficial mental health intervention in a developing country that may increase compliance with medication and result in greater knowledge of mental illness. However, other factors such as distance from a centralized clinic or cost of treatment may impact outcomes, including attendance at scheduled follow-up visits.

In vitro protective effects of colon-available extract of Camellia sinensis (tea) against hydrogen peroxide and beta-amyloid (Aß((1-42))) induced cytotoxicity in differentiated PC12 cells.

There is mounting evidence that the deposition and aggregation of ß-amyloid peptides (Aß) in the brain play a significant role in the development and pathogenesis of Alzheimer's disease. There is further evidence that free radical species such as hydrogen peroxide (H(2)O(2)) mediate Aß induced toxicity. Previous studies have demonstrated that green tea polyphenols possess neuroprotective properties through their ability to ameliorate oxidative stress induced by free radical species. Green tea polyphenols have also been shown to enhance cognition in various animal models of induced cognitive impairment. Upon ingestion, green tea polyphenols are metabolised and undergo bio-transformation which affects their bioavailability and therefore efficacy. In this study, a green tea extract was subjected to a simulated gastrointestinal digestion and a 'colon-available' extract (CAGTE) prepared and assessed for its potential protective effects against H(2)O(2) and Aß((1-42)) induced cytotoxicity using differentiated PC12 cells (dPC12) as a model for neuronal cells. CAGTE represents green tea phytochemicals potentially available after upper gastrointestinal digestion. CAGTE which was depleted in flavan-3-ols, as shown by LC-MS analysis, protected dPC12 cells at concentration ranges of 0.3-10 µg/ml and 0.03-0.125 µg/ml for H(2)O(2) and Aß((1-42)), induced cytotoxicity, respectively. At high concentrations, CAGTE exhibited direct anti-proliferative effects, in line with the reputed anti-cancer properties of green tea polyphenols. These results demonstrate that potentially bioavailable green tea metabolites are able to ameliorate both H(2)O(2) and Aß((1-42)) induced cytotoxicity.

Gender-based profiling of Quality of Life (QOL) of primary health care (PHC) attendees in central Uganda: a cross sectional analysis.

OBJECTIVE: To analyze gender differences in QOL of patients presenting at PHC centres and to identify the socio-demographic variables associated with poor QOL. METHODS: This was a cross-sectional study. Consecutive adult patients at outpatient departments of three PHC centres were eligible. Those selected were interviewed using the WHOQOL-BREF, a 26-item questionnaire generating four domain scores of physical, psychological, environment and social relationships. RESULTS: The study had 446 respondents aged 18-84 years. Female parents significantly performed poorly on the physical health domain (OR 2.47: 95 % CI: 1.32 - 4.61). Respondents reported comparable scores on the 3 WHOQOL-BREF domains, except on poor physical health where being a parent had a positive association (OR 2.12; 95% CI: 1.27 - 3.55). Belonging to an age-range of 18-29 years had a positive association with poor physical health (OR 1.74; 95% CI: 1.13 - 2.68). CONCLUSION: Generally, women reported poorer physical health. Health workers need orientation and training to appreciate the role of gender in health care. There is need to appreciate the complexities affecting QOL of women that are physically ill. Interventions aimed at improving patients' QOL at PHC centres should take a gender-based perspective that recognizes the greater vulnerability of women to poor physical health.

Treatment with spironolactone for 24 weeks decreases the level of matrix metalloproteinases and improves cardiac function in patients with chronic heart failure of ischemic etiology.

BACKGROUND: The myocardial extracellular matrix is believed to be central to the remodelling that takes place following myocardial infarction. The contribution of markers of collagen metabolism to this process remains less well understood. The present study examined the contribution of some of the markers of collagen metabolism in cardiac remodelling, as well as the effect of spironolactone on the remodelling process. OBJECTIVES: To investigate the pathological contribution of markers of collagen metabolism, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), type I collagen carboxyterminal telopeptide (ICTP) and procollagen type I carboxyterminal propeptide (PICP), in cardiac remodelling following ischemic cardiomyopathy, and to examine the pharmacoregulatory effects of spironolactone on collagen metabolism. METHOD: Eighty-six consecutive patients (62 men and 24 women) with chronic heart failure of ischemic etiology (patient group) and 25 age-matched controls were enrolled in the study. The subjects in the patient group were randomly assigned into a spironolactone or nonspironolactone group. Plasma levels of MMP-9, TIMP-1, ICTP and PICP were measured using ELISA and radioimmunoassay techniques. Furthermore, left ventricular diastolic diameter and ejection fraction were assessed using two-dimensional and Doppler echocardiography. RESULTS: The plasma concentrations of MMP-9, TIMP-1 and the MMP-9 to TIMP-1 ratio, as well as ICTP, were significantly increased in the patient group. The PICP to ICTP ratio in the patient group was significantly lower than that in the age-matched control subjects. After a follow-up period of 24 weeks, the PICP to ICTP ratio increased, and MMP-9, TIMP-1 and the MMP-9 to TIMP-1 ratio decreased in the spironolactone subgroup. CONCLUSIONS: Biomarkers of collagen degradation were elevated and correlated with depressed heart function; spironolactone may partially reverse the dysregulation in collagen metabolism.