Information for decision making from imperfect national data: tracking major changes in health care use in Kenya using geostatistics

Background

Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects.

Methods

Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT.

Results

A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 ± 45 IU/L and 55 ± 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group.

Conclusion

Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.     

The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection

Introduction

Helicobacter pylori infection is associated with decreased alcohol dehydrogenase (ADH) activity in the gastric mucosa. The decrease in gastric ADH activity depends on the severity of inflammation and mucosal injury. This damage can be a reason of the release of enzyme from gastric mucosa and leads to the increase of the ADH activity in the sera of patients with H. pylori infection.

Material and methods

Serum samples were taken from 140 patients with H. pylori infection. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate.

Results

The activity of ADH IV in the serum of patients with H. pylori infection increased about 42% (7.86 mU/l) in the comparison to the control level (4.52 mU/l). Total activity of ADH was 1105 mU/l in patients group and 682 mU/l in control. The diagnostic sensitivity for ADH IV was 88%, specificity 90%, positive and negative predictive values were 91% and 84% respectively. Area under ROC curve for ADH IV was 0.84.

Conclusions

Helicobacter pylori infection of gastric mucosa is reflected in the serum by significant increase of class IV and total ADH activity. The results suggest a potential role for ADH IV as a marker of H. pylori infection.     

Asialoglycoprotein receptor interacts with the preS1 domain of hepatitis B virus in vivo and in vitro

Background

The preS1 domain of the large envelope protein has been identified as an essential viral structure involved in hepatitis B virus (HBV) attachment. However, the cellular receptor(s) for HBV has not yet been identified.

Aims

To identify a cell-surface receptor for HBV, which could elucidate the molecular mechanism of HBV infection.

Methods

A novel yeast two-hybrid system was used to screen proteins interacting with the preS1 region of HBV. Their interaction was verified by yeast cotransformation, coimmunoprecipitation and mammalian two-hybrid assay, while their intracellular and tissue localization was analyzed by confocal microscopy and immunohistochemistry, respectively.

Results

Asialoglycoprotein receptor (ASGPR) interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro. The levels of expression of preS1 and ASGPR in the liver were similar and correlated with each other.

Conclusions

ASGPR is a candidate receptor for HBV that mediates further steps of HBV entry.     

The alterations in alcohol dehydrogenase and aldehyde dehydrogenase activities in the sera of patients with renal cell carcinoma

Purpose

In a previous study we showed that the total activity of alcohol dehydrogenase (ADH) and its isoenzyme class I was significantly higher in renal cancer (RCC) cells compared to normal kidney. The aim of this study was to compare the activities of ADH isoenzymes and aldehyde dehydrogenase (ALDH) in the sera of patients with different stages of RCC and healthy subjects.

Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients

Objective

We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn’s disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis.

Subjects

We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants.

Methods

The analysis was carried out using PCR–RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls.

Results

We observed no significant difference of the examined variants between the patient and control groups.

Conclusions

Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.     

Effect of a Telephone-Delivered Coronary Heart Disease Secondary Prevention Program (ProActive Heart) on Quality of Life and Health Behaviours: Primary Outcomes of a Randomised Controlled Trial

Background

Participation in coronary heart disease secondary prevention programs is low. Innovative programs to meet this treatment gap are required.

Purpose

To aim of this study is to describe the effectiveness of a telephone-delivered secondary prevention program for myocardial infarction patients.

Methods

Four hundred and thirty adult myocardial infarction patients in Brisbane, Australia were randomised to a 6-month secondary prevention program or usual care. Primary outcomes were health-related quality of life (Short Form-36) and physical activity (Active Australia Survey).

Results

Significant intervention effects were observed for health-related quality of life on the mental component summary score (p?=?0.02), and the social functioning (p?=?0.04) and role-emotional (p?=?0.03) subscales, compared with usual care. Intervention participants were also more likely to meet recommended levels of physical activity (p?=?0.02), body mass index (p?=?0.05), vegetable intake (p?=?0.04) and alcohol consumption (p?=?0.05).

Conclusions

Telephone-delivered secondary prevention programs can significantly improve health outcomes and could meet the treatment gap for myocardial infarction patients.     

Managing stress and anxiety through qigong exercise in healthy adults: a systematic review and meta-analysis of randomized controlled trials

Background

Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats.

Methods

Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated.

Results

Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio.

Conclusions

Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress.     

S-adenosylmethionine decreases the peak blood alcohol levels 3 h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver

Introduction

An alcohol bolus causes the blood alcohol level (BAL) to peak at 1–2 h post ingestion. The ethanol elimination rate is regulated by alcohol metabolizing enzymes, primarily alcohol dehydrogenase (ADH1), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 (CYP2E1). Recently, S-adenosylmethionine (SAMe) was found to reduce acute BALs 3 h after an alcohol bolus. The question, then, was: what is the mechanism involved in this reduction of BAL by feeding SAMe? To answer this question, we investigated the changes in ethanol metabolizing enzymes and the epigenetic changes that regulate the expression of these enzymes during acute binge drinking and chronic drinking.

Methods

Rats were fed a bolus of ethanol with or without SAMe, and were sacrificed at 3 h or 12 h after the bolus.

Results

RT-PCR and Western blot analyses showed that SAMe significantly induced ADH1 levels in the 3 h liver samples. However, SAMe did not affect the changes in ADH1 protein levels 12 h post bolus. Since SAMe is a methyl donor, it was postulated that the ADH1 gene expression up regulation at 3 h was due to a histone modification induced by methylation from methyl transferases. Dimethylated histone 3 lysine 4 (H3K4me2), a modification responsible for gene expression activation, was found to be significantly increased by SAMe at 3 h post bolus.

Conclusion

These results correlated with the low BAL found at 3 h post bolus, and support the concept that SAMe increased the gene expression to increase the elimination rate of ethanol in binge drinking by increasing H3K4me2.     

Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism

Purpose

β3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18–75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease.

Method

Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake ( \(\dot V\) O_2peak) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of \(\dot V\) O_2peak for sex and decade.

Results

Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and \(\dot V\) O_2peak were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects.

Conclusion

Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.     

Depressive Symptoms are Associated with Lower Bone Mineral Density in Young Adults with High Job Strain. The Cardiovascular Risk in Young Finns Study

Background

Job strain has been associated with depressive symptoms, and depression has been associated with low bone mineral density (BMD).

Purpose

The associations between BMD and job strain have not been studied. We examined the relations between BMD, job strain, and depressive symptoms in a population-based group of young adults in Finland.

Method

Ultrasonic measurement of BMD at the calcaneus was performed on 777 participants (men 45 %, aged 30–45) drawn from the Cardiovascular Risk in Young Finns Study. Job strain was assessed by self-administered questionnaires by the combination of job demands and job control. Depressive symptoms were assessed with a modified Beck Depression Inventory. The effects of job strain on BMD were studied with multivariable analyses with age, sex, BMI, vitamin D, and calcium intake, physical activity, cigarette smoking, alcohol use, and depressive symptoms as covariates.

Results

Depressive symptoms were independently associated with lower BMD T score in participants with high job strain (β?=??0.241, p?=?0.02), but depressive symptoms were not significantly associated with BMD in the low (β?=??0.160, p?=?0.26) and intermediate (β?=??0.042, p?=?0.66) job strain categories.

Conclusion

The results suggest that job strain modifies the association between depressive symptoms and BMD. Depressed individuals with high work-related stress might be in increased risk of lower bone mineral density.     

Lack of association between IL-23R gene polymorphisms and systemic lupus erythematosus in a Chinese population

Objective

The aim to this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of interleukin (IL)-23 receptor gene and systemic lupus erythematosus (SLE) in a Chinese population.

Methods

A case–control study was performed to investigate the associations of SNPs in IL-23R gene (rs10889677 and rs1884444) with susceptibility to SLE in 521 Chinese SLE patients and 527 normal controls. The chi-square test and unconditional Logistic regression were used to analysis by SPSS 10.1 software.

Results

No significant differences were detected for the distribution of allele and genotype frequencies of these two SNPs between patients and controls as well as SLE patients with nephritis (LN) and those without nephritis.

Conclusion

The findings suggest that the polymorphisms of IL-23R gene might not contribute to the susceptibility of SLE in the Chinese population.     

Role of neurokinin 1 receptors in dextran sulfate-induced colitis: studies with gene-deleted mice and the selective receptor antagonist netupitant

Objective and design

The function of the neurokinin 1 (NK1) receptor was investigated in the DSS-induced mouse colitis model using NK1 receptor-deficient mice and the selective antagonist netupitant.

Subjects

Colitis was induced by oral administration of 20 mg/ml DSS solution for 7 days in C57BL/6 and Tacr1 KO animals (n = 5–7).

Treatment

During the induction, one-half of the C57BL/6 and Tacr1 KO group received one daily dose of 6 mg/kg netupitant, administered intraperitoneally, the other half of the group received saline, respectively.

Methods

Disease activity index (DAI), on the basis of stool consistency, blood and weight loss, was determined over 7 days. Histological evaluation, myeloperoxidase (MPO) measurement, cytokine concentrations and receptor expression analysis were performed on the colon samples.

Results

NK1 receptors are up-regulated in the colon in response to DSS treatment. DSS increased DAI, histopathological scores, BLC, sICAM-1, IFN-γ, IL-16 and JE in wildtype mice, which were significantly reduced in NK1 receptor-deficient ones. NK1 receptor antagonism with netupitant significantly diminished DAI, inflammatory histopathological alterations, BLC, IFN-γ, IL-13 and IL-16 in wildtype mice, but not in the NK1-deficient ones. MPO was similarly elevated and netupitant significantly decreased its activity in both groups.

Conclusions

NK1 receptor antagonism could be beneficial for colitis via inhibiting different inflammatory mechanisms.     

Antimicrobial activities of the methanol extract and compounds from Artocarpus communis (Moraceae)

Background

Artocarpus communis is used traditionally in Cameroon to treat several ailments, including infectious and associated diseases. This work was therefore designed to investigate the antimicrobial activities of the methanol extract (ACB) and compounds isolated from the bark of this plant, namely peruvianursenyl acetate C (1), α-amyrenol or viminalol (2), artonin E (4) and 2-[(3,5-dihydroxy)-(Z)-4-(3-methylbut-1-enyl)phenyl]benzofuran-6-ol (5).

Methods

The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species.

Results

The MIC results indicated that ACB as well as compounds 4 and 5 were able to prevent the growth of all tested microbial species. All other compounds showed selective activities. The lowest MIC value of 64 μg/ml for the crude extract was recorded on Staphylococcus aureus ATCC 25922 and Escherichia coli ATCC 8739. The corresponding value of 32 μg/ml was recorded with compounds 4 and 5 on Pseudomonas aeruginosa PA01 and compound 5 on E. coli ATCC 8739, their inhibition effect on P. aeruginosa PA01 being more than that of chloramphenicol used as reference antibiotic.

Conclusion

The overall results of this study provided supportive data for the use of A. communis as well as some of its constituents for the treatment of infections associated with the studied microorganisms.     

Viral Suppression and Antiretroviral Medication Adherence Among Alcohol Using HIV-Positive Adults

Background

Substance use is a known predictor of poor adherence to antiretroviral therapies (ART) in people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Less studied is the association between substance use and treatment outcomes, namely, suppression of HIV replication.

Methods

Adults living with HIV (N?=?183) who reported alcohol use in the previous week and receiving ART were observed over a 12-month period. Participants completed computer interviews, monthly unannounced pill counts to monitor ART adherence, and daily cell-phone delivered interactive-text assessments for alcohol use. HIV viral load was collected at baseline and 12-month follow-up from medical records. Analyses compared participants who had undetectable HIV viral loads at baseline and follow-up (sustained viral suppression) to those with unsustained viral suppression. Analyses also compared participants who were adherent to their medications (>85 % pills taken) over the year of observation to those who were nonadherent.

Results

Fifty-two percent of participants had unsustained viral suppression; 47 % were ART nonadherent. Overall results failed to demonstrate alcohol use as a correlate of sustained viral suppression or treatment adherence. However, alcohol use was associated with nonadherence among participants who did not have sustained viral suppression; nonadherence in unsustained viral suppression patients was related to drinking on fewer days of assessment, missing medications when drinking, and drinking socially.

Conclusions

Poor HIV treatment outcomes and nonadherence were prevalent among adults treated for HIV infection who drink alcohol. Drinking in relation to missed medications and drinking in social settings are targets for interventions among alcohol drinkers at greatest risk for poor treatment outcomes.     

BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal plants

Background

The roots of Sophora flavescens (Leguminosae) have been used in East Asian countries as an herbal medicine and a food ingredient for thousands of years. The aim of the present study was to investigate the effects of S. flavescens fermentation on endotoxin-induced uveitis (EIU) in rats.

Methods

EIU was induced in rats via a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, fermented and non-fermented extracts of S. flavescens (FSE and NFSE, respectively) were administered orally, and the aqueous humor was collected from both eyes 24 hours later. The anti-inflammatory effects of FSE and NFSE were examined in terms of regulation of nuclear factor kappa B (NF-κB) activation and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular cell adhesion molecule (ICAM)-1, and cyclooxygenase-2 (COX-2). The regulation of maleic dialdehyde (MDA) levels and polymorphonuclear cell (PMN) infiltration by FSE and NFSE were also examined.

Results

Treatment with FSE significantly inhibited LPS-induced increases in IL-1β and TNF-α production and the expression of iNOS, ICAM-1 and COX-2. Moreover, FSE suppressed LPS-induced NF-κB activation, and reduced both MDA levels and infiltration by PMN.

Conclusion

These results indicate that solid state fermentation may enhance the anti-inflammatory effects of S. flavescens.     

Identifying the Zheng in psoriatic patients based on latent class analysis of traditional Chinese medicine symptoms and signs

Background

There are approximately five Zhengs reported in psoriatic patients. Systematic data collection and proper analysis for the classification of psoriasis have been lacking. This study aims to cluster the Zhengs in psoriatic patients based on the application of a checklist of traditional Chinese medicine (TCM) symptoms and signs followed by latent class analysis (LCA).

Methods

A cross-sectional study of 507 psoriatic patients aged above 10 years was performed in Yunnan Provincial Hospital of TCM and the First Affiliated Hospital of Kunming Medicine University from October 2010 to September 2011 using a TCM symptoms and signs checklist obtained from 16 TCM experts by the Delphi technique. LCA was applied to obtain the best fitted model for clustering of symptoms and signs that can be interpreted as underlying Zhengs of psoriasis.

Results

The LCA identified three Zhengs: dampness-heat Zheng (35.1%); blood heat Zheng (34.7%); and yin deficiency and blood dryness Zheng (30.2%). The first Zheng was associated with winter, the second with male sex, old age, smoking, and drinking alcohol, and the third with outpatient status, which reflected a mild disease course.

Conclusions

In this study, 507 psoriasis patients were clustered into three Zhengs, which had different associated factors.