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Human & Experimental Toxicology Sep 2011Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as... (Review)
Review
Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.
Topics: Animals; Carbamates; Carbohydrate Metabolism; Databases, Bibliographic; Humans; Hydrocarbons, Chlorinated; Lipid Metabolism; Metabolic Diseases; Organophosphates; Oxidative Stress; Pesticides; Proteins
PubMed: 21071550
DOI: 10.1177/0960327110388959 -
The Cochrane Database of Systematic... Apr 2008Alzheimer's disease (AD) has become a major public health problem around the world due to its increasing prevalence, long duration, caregiver burden, and high financial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease (AD) has become a major public health problem around the world due to its increasing prevalence, long duration, caregiver burden, and high financial cost of care. The degeneration of acetylcholine-containing neurons in the basal forebrain has been implicated in the symptoms of AD. Cholinesterase inhibitors may block the degradation of acetylcholine, thus increasing the efficacy of the remaining cholinergic neurons. Huperzine A is a linearly competitive, reversible inhibitor of acetyl cholinesterase that is said to have both central and peripheral activity with the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These properties might qualify Huperzine A as a promising agent for treating dementia (including AD).
OBJECTIVES
To assess the efficacy and safety of Huperzine A for the treatment of patients with AD.
SEARCH STRATEGY
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 1 February 2006 using the search term: huperzin*. The CDCIG Specialized register contains records from all major health care databases (MEDLINE, EMBASE, PsycINFO, CINAHL, SIGLE, ISTP, INSIDE, LILACS) as well as from many trials databases and grey literature sources. In addition, the CBM and AMED databases and relevant websites were searched and some journals were hand-searched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references.
SELECTION CRITERIA
All relevant randomized controlled trials (RCTs) studying the efficacy and safety of Huperzine A for AD.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two reviewers using a self-developed data extraction form and entered into RevMan 4.2.10 software. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Random effects analyses were performed whenever heterogeneity between results appeared to be present. Standardized differences in mean outcome measures were used due to the use of different scales and periods of treatment.
MAIN RESULTS
Six trials including a total of 454 patients met our inclusion criteria. The methodological quality of most included trials was not high. It was shown that compared to placebo, Huperzine A had beneficial effects on the improvement of general cognitive function measured by MMSE (WMD 2.81; 95% CI 1.87 to 3.76; P < 0.00001) and ADAS-Cog at six weeks (WMD 1.91; 95% CI 1.27 to 2.55) and at 12 weeks (WMD 2.51; 95% CI 1.74 to 3.28), global clinical assessment measured by CDR (WMD -0.80; 95% CI -0.95 to -0.65) and CIBIC-plus (OR 4.32, 95% CI 2.37 to 7.90), behavioral disturbance measured by ADAS-non-Cog at six weeks (WMD -1.33, 95%CI -2.12 to -0.54) and at 12 weeks (WMD -1.52, 95% CI-2.39 to -0.65), and functional performance measured by ADL (WMD = -7.17; 95% CI -9.13 to -5.22; P < 0.00001). However, Huperzine A was not superior to placebo in the improvement of general cognitive function measured by Hasegawa Dementia Scale (HDS) (WMD: 2.78; 95% CI -0.17 to 5.73, P = 0.06) and specific cognitive function measured by Weshler Memory Scale (WMS) (WMD = 6.64; 95% CI -3.22 to 16.50; P = 0.19). No data were available on quality of life and caregiver burden. The adverse events of Huperzine A were mild and there were no significant differences of adverse events between Huperzine A groups and control groups.
AUTHORS' CONCLUSIONS
From the available evidence, Huperzine A seems to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance, with no obvious serious adverse events for patients with AD. However, only one study was of adequate quality and size. There is therefore inadequate evidence to make any recommendation about its use. Rigorous design, randomized, multi-centre, large-sample trials of Huperzine A for AD are needed to further assess the effects.
Topics: Alkaloids; Alzheimer Disease; Cholinesterase Inhibitors; Humans; Randomized Controlled Trials as Topic; Sesquiterpenes
PubMed: 18425924
DOI: 10.1002/14651858.CD005592.pub2 -
American Journal of Epidemiology Oct 2007Bladder cancer is an increasingly important international public health problem, with over 330,000 new cases being diagnosed each year worldwide. In a systematic review... (Meta-Analysis)
Meta-Analysis Review
Joint effects of the N-acetyltransferase 1 and 2 (NAT1 and NAT2) genes and smoking on bladder carcinogenesis: a literature-based systematic HuGE review and evidence synthesis.
Bladder cancer is an increasingly important international public health problem, with over 330,000 new cases being diagnosed each year worldwide. In a systematic review and evidence synthesis, the authors investigated the joint effects of the N-acetyltransferase genes NAT1 and NAT2 and cigarette smoking on bladder carcinogenesis. Studies were identified through an exhaustive search of multiple electronic databases and reference lists and through direct contact with study authors and experts. Random-effects meta-analysis was used within a Bayesian framework to investigate individual effects of NAT1 and NAT2 acetylation status on bladder cancer risk, while a novel approach was used to investigate joint effects of these two genes with cigarette smoking. An increased risk of bladder cancer was found in NAT2 slow acetylators (odds ratio = 1.46, 95% credible interval (CI): 1.26, 1.68) but not in NAT1 fast acetylators (odds ratio = 1.01, 95% CI: 0.86, 1.22). The joint effects in the highest risk category (NAT2 slow acetylator, NAT1 fast acetylator, and current or ever cigarette smoking) as compared with the reference category (NAT2 fast acetylator, NAT1 slow acetylator, and never smoking) were associated with an odds ratio of 2.73 (95% CI: 1.70, 4.31). The importance of considering joint effects between genetic and environmental factors in the etiology of common complex diseases is underlined.
Topics: Amines; Arylamine N-Acetyltransferase; Bayes Theorem; Genetic Variation; Genotype; Humans; Isoenzymes; Polymorphism, Genetic; Risk Assessment; Risk Factors; Smoking; United Kingdom; Urinary Bladder Neoplasms
PubMed: 17675654
DOI: 10.1093/aje/kwm167 -
Intensive Care Medicine Jul 2007To appraise the literature on the value of urinary biomarkers in septic acute kidney injury (AKI). (Review)
Review
OBJECTIVE
To appraise the literature on the value of urinary biomarkers in septic acute kidney injury (AKI).
DESIGN
Systematic review.
SETTING
Academic medical centre.
PATIENTS AND PARTICIPANTS
Human studies of urinary biomarkers.
INTERVENTIONS
None.
MEASUREMENTS AND RESULTS
Fourteen articles fulfilled inclusion criteria. Most studies were small, single-centre, and included mixed medical/surgical adult populations. Few focused solely on septic AKI and all had notable limitations. Retrieved articles included data on low-molecular-weight proteins (beta2-microglobulin, alpha1-microglobulin, adenosine deaminase binding protein, retinol binding protein, cystatin C, renal tubular epithelial antigen-1), enzymes (N-acetyl-beta-glucosaminidase, alanine-aminopeptidase, alkaline phosphatase; lactate dehydrogenase, alpha/pi-glutathione-S-transferase, gamma-glutamyl transpeptidase), cytokines [platelet activating factor (PAF), interleukin-18 (IL-18)] and other biomarkers [kidney injury molecule-1, Na/H exchanger isoform-3 (NHE3)]. Increased PAF, IL-18, and NHE3 were detected early in septic AKI and preceded overt kidney failure. Several additional biomarkers were evident early in AKI; however, their diagnostic value in sepsis remains unknown. In one study, IL-18 excretion was higher in septic than in non-septic AKI. IL-18 also predicted deterioration in kidney function, with increased values preceding clinically significant kidney failure by 24-48 h. Detection of cystatin C, alpha1-microglobulin, and IL-18 predicted need for renal replacement therapy (RRT).
CONCLUSIONS
Few clinical studies of urinary biomarkers in AKI have included septic patients. However, there is promising evidence that selected biomarkers may aid in the early detection of AKI in sepsis and may have value for predicting subsequent deterioration in kidney function. Additional prospective studies are needed to accurately describe their diagnostic and prognostic value in septic AKI.
Topics: Acute Disease; Biomarkers; Cytokines; Enzymes; Humans; Proteinuria; Renal Insufficiency; Sepsis
PubMed: 17487471
DOI: 10.1007/s00134-007-0656-5 -
The Cochrane Database of Systematic... Oct 2006Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. The coronary arteries supplying the heart can be damaged in... (Review)
Review
BACKGROUND
Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. The coronary arteries supplying the heart can be damaged in Kawasaki disease. The principal advantage of timely diagnosis is the potential to prevent this complication with early treatment. Salicylate (acetyl salicylate acid (ASA), aspirin) and intravenous immunoglobulin (IVIG) are widely used for this purpose. Salicylate is largely otherwise avoided in children because of concerns about serious side effects, particularly the risk of Reyes syndrome.
OBJECTIVES
The objective of this review was to evaluate the effectiveness of salicylate in treating and preventing cardiac consequences of Kawasaki disease in children.
SEARCH STRATEGY
The Cochrane Peripheral Vascular Disease Group searched their trials register (last searched July 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 3, 2006). We searched MEDLINE (January 1966 to July 2006), EMBASE (January 1980 to July 2006), and CINAHL (1982 to July 2006), and reference list of articles. In addition we contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of salicylate to treat Kawasaki disease in children were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.
MAIN RESULTS
We found one trial involving 102 children which was described as randomised, but it was not possible to confirm the method of treatment allocation. A second comparative study, possibly with a randomised treatment allocation, was also identified. The one randomised trial reported no association between the addition of ASA to IVIG treatment on the rate of coronary artery abnormalities at follow up, but with wide confidence limits. The second, possibly randomised trial did demonstrate a reduction in duration of fever with high dose ASA compared to low dose ASA, but was insufficiently powered to establish the effect on coronary artery abnormalities at follow up.
AUTHORS' CONCLUSIONS
Until good quality RCTs are carried out, there is insufficient evidence to indicate whether children with Kawasaki disease should continue to receive salicylate as part of their treatment regimen.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Child; Humans; Immunoglobulins, Intravenous; Mucocutaneous Lymph Node Syndrome; Salicylates
PubMed: 17054199
DOI: 10.1002/14651858.CD004175.pub2 -
BMC Medical Genetics Jul 2006N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is polymorphic, thus resulting in rapid or slow acetylator phenotypes. The acetylator status may, therefore, predispose drug-induced toxicities and cancer risks, such as bladder, colon and lung cancer. Indeed, some studies demonstrate a positive association between NAT2 rapid acetylator phenotype and colon cancer, but results are inconsistent. The role of NAT2 acetylation status in lung cancer is likewise unclear, in which both the rapid and slow acetylator genotypes have been associated with disease.
METHODS
We investigated three genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), of the NAT2 gene, which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects, 92 colon and 67 lung cancer patients for these genetic variations. As there is a recent meta-analysis of NAT2 studies on colon cancer (unlike in lung cancer), we have also undertaken a systematic review of NAT2 studies on lung cancer, and we incorporated our results in a meta-analysis consisting of 16 studies, 3,865 lung cancer patients and 6,077 control subjects.
RESULTS
We did not obtain statistically significant differences in NAT2 allele and genotype frequencies in colon cancer patients and control group. Certain genotypes, however, such as [c.590AA+c.857GA] and [c.590GA+c.857GA] were absent among the colon cancer patients. Similarly, allele frequencies in lung cancer patients and controls did not differ significantly. Nevertheless, there was a significant increase of genotypes [c.590GA] and [c.481CT+c.590GA], but absence of homozygous c.590AA and [c.590AA+c.857GA] in the lung cancer group. Meta-analysis of 16 NAT2 studies on lung cancer did not evidence an overall association of the rapid or slow acetylator status to lung cancer. Similarly, the summary odds ratios obtained with stratified meta-analysis based on ethnicity, and smoking status were not significant.
CONCLUSION
Our study failed to show an overall association of NAT2 genotypes to either colon or lung cancer risk.
Topics: Arylamine N-Acetyltransferase; Case-Control Studies; Colonic Neoplasms; Gene Frequency; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Polymorphism, Single Nucleotide; White People
PubMed: 16827944
DOI: 10.1186/1471-2350-7-58 -
BMC Medical Genetics Mar 2006Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.
METHODS
We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.
RESULTS
Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12-1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9-1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well.
CONCLUSION
We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.
Topics: Arylamine N-Acetyltransferase; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide
PubMed: 16571112
DOI: 10.1186/1471-2350-7-30 -
Gastroenterology Aug 2001Increasingly, studies of the relationship between common genetic variants and colorectal tumor risk are being proposed. To assess the evidence that any of these confers... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Increasingly, studies of the relationship between common genetic variants and colorectal tumor risk are being proposed. To assess the evidence that any of these confers a risk, a systematic review and meta-analysis of published studies was undertaken.
METHODS
Fifty studies of the effect of common alleles of 13 genes on risk were identified. To clarify the impact of individual polymorphisms on risk, pooled analyses were performed.
RESULTS
Of the 50 studies identified, significant associations were seen in 16, but only 3 were reported in more than one study. Pooling studies, significant associations were only seen for 3 of the polymorphisms: adenomatosis polyposis coli (APC)-I1307K (odds ratio [OR] = 1.58, 95% confidence interval [CI]: 1.21-2.07); Harvey ras-1 variable number tandem repeat polymorphism (HRAS1-VNTR; OR = 2.50, 95% CI: 1.54-4.05); and methylenetetrahydrofolate reductase (MTHFR)(Val/Val) (OR = 0.76, 95% CI: 0.62-0.92). For tumor protein 53 (TP53), N-acetyl transferase 1 (NAT1), NAT2, glutathione-S transferase Mu (GSTM1), glutathione-S transferase Theta (GSTT1), and glutathione-S transferase Pi (GSTP1) polymorphisms, the best estimates are sufficient to exclude a 1.7-fold increase in risk of colorectal cancer.
CONCLUSIONS
APC-I1307K, HRAS1-VNTR, and MTHFR variants represent the strongest candidates for low penetrance susceptibility alleles identified to date. Although their genotypic risks are modest, their high frequency in the population implies that they may well have considerable impact on colorectal cancer incidence. Determining precise risk estimates associated with other variants and gene-gene and gene-environment interactions will be contingent on further studies with sample sizes larger than typically used to date.
Topics: Colorectal Neoplasms; DNA Methylation; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Humans; Oncogenes; Polymorphism, Genetic; Risk Factors
PubMed: 11487538
DOI: 10.1053/gast.2001.26265