Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a ...relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity.
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•Valproic acid (VPA) is an antiepileptic drug used in epilepsy and psychiatric disorders•VPA has good efficacy and pharmacoeconomic profiles•VPA adverse drug reactions encompass a broad spectrum•VPA produces both acute liver failure and chronic liver damage•VPA induces metabolic and endocrine adverse events, as well as teratogenicity
Hyaluronic acid and wound healing Neuman, Manuela G; Nanau, Radu M; Oruña-Sanchez, Loida ...
Journal of pharmacy & pharmaceutical sciences,
01/2015, Letnik:
18, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We developed an experimental model of ethanol-induced dermatotoxicity and hepatocytoxicity using normal human keratinocytes and normal human hepatocytes that preserve inducible cytochrome p450 ...activities. The original work was described in several articles. The objective of this study was to determine whether hyaluronic acid attenuates skin necrosis, and to further clarify its uses in wound repair in humans, animal models and in vitro studies.
We performed a systematic review of the literature using the terms "hyaluronic acid" and "wound healing". PubMed was searched for studies published during the period 2010-2014.
Hyaluronic acid is used in tissue regeneration alone or in combination with herbal or Western medicine. Scaffolds made up of hyaluronic acid were used to embed basic fibroblast growth factor.
Hyaluronic acid extracts are safe and efficacious products to be used in skin repair.
Inflammatory bowel disease (IBD) encompassed several chronic inflammatory disorders leading to damage of the gastrointestinal tract (GI). The 2 principal forms of these disorders are ulcerative ...colitis (UC) and Crohn disease (CD). Bacteria are involved in the etiology of IBD, and the genetic susceptibility, environmental factors, and lifestyle factors can affect the individual's predisposition to IBD. The review discusses the potential role of environmental factors such as diet and microbiota as well as genetics in the etiology of IBD. It is suggested that microbial ecosystem in the human bowel colonizing the gut in many different microhabitats can be influence by diet, leading to formation of metabolic processes that are essential form the bowel metabolism.
The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human ...immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior.
A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010-2015). The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers.
Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.
Biomarkers in nonalcoholic fatty liver disease Neuman, Manuela G; Cohen, Lawrence B; Nanau, Radu M
Canadian journal of gastroenterology & hepatology,
12/2014, Letnik:
28, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and ...progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers.
To review the biomarkers used to diagnose and define the severity of NAFLD and NASH.
A comprehensive PubMed and Google Scholar literature search was performed using the terms "non-alcoholic fatty liver disease", "non-alcoholic steatohepatitis", as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed.
Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity.
The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.
Chronic liver diseases may cause inflammation and progressive scarring, over time leading to irreversible hepatic damage (cirrhosis). As a result, the need to assess and closely monitor individuals ...for risk factors of components of matrix deposition and degradation, as well as the severity of the fibrosis using biomarkers, has been increasingly recognized.
Our aim is to review the use of biomarker for diagnosing and defining the severity of liver fibrosis.
A systematic literature review was done using the terms “hyaluronic acid” and “liver fibrosis” as well as the name of each biomarker or algorithm known to be employed. PubMed and Google Scholar were searched, and English language articles indexed between January 2010 and October 2014 in which HA was used as a marker of liver fibrosis were retrieved, regardless of the underlying liver disease. Each author read the publications separately and the results were analyzed and discussed.
Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression, or both. Serum biomarkers, including HA, have been used for many years.
Emerging biomarkers such as metalloproteinases have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of extracellular matrix degradation provide powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender and ethnic origin are a necessity.
This review attempts to provide a comprehensive analysis of the emerging risk biomarkers of liver fibrosis and to describe the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.
•Hyaluronic acid (HA) is a non-invasive biomarker, used alone or in combination with other markers to determine the degree of fibrosis.•HA sensitivity and specificity limit its use.•Different algorithms in which HA is part of the equation are suggested for fibrosis of liver illnesses.•Liver biopsy remains the gold standard of histological activity index/ inflammation and fibrosis in diagnosis of liver damage.•HA and other matrix markers should be employed to monitor the liver fibrosis in time and/or during therapies.
Hepatotoxicity of Pyrrolizidine Alkaloids Neuman, Manuela G; Cohen, Lawrence; Opris, Mihai ...
Journal of pharmacy & pharmaceutical sciences,
01/2015, Letnik:
18, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This article aimed 1) to review herbal medicine containing pyrrolizidine alkaloids (PA)-induced toxicities of the liver; 2) to encourage the recognition and prevention of common problems encountered ...when using complementary and alternative medicine and 3) to review the toxic effects of herbal remedies containing PAs.
We performed a systematic literature search using the PubMed and Google Scholar engines. The search was not restricted to languages. We also provide an interpretation of the data.
Herbal remedies containing PAs can induce liver damage, including hepato- sinusoidal obstruction syndrome or veno-occlusive disease. Preventing overdose and monitoring long-term use of such remedies may avoid glutathione depletion leading to mitochondrial injury, and therefore avoid liver cell damage. Moreover, immediately stopping the herbal medication prevents further harm to the liver. Chronic consumption of hepatotoxicants can lead to cancer formation and promotion. The role of active metabolites in PA-induced liver toxicity and their mechanism of action require further investigation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Inflammatory and rheumatic arthritis remain leading causes of disability worldwide. The arthritis therapeutic area commands the largest market for the prescription of biological and non-steroidal ...anti-inflammatory drugs (NSAID). Yet biotechnology and pharmaceutical companies conducting research and providing therapeutics in this area frequently face challenges in patient safety. The purpose of our study was to assess safety of anti-tumor necrosis factor therapies in arthritis patients.
The present study systematically reviews adverse events of biologicals alone or in the presence of NSAIDs and other immunosuppressant therapeutics such as disease-modifying antirheumatic drugs (DMARD). We assessed the rheumatology literature that included clinical trials with anti-tumor necrosis factor (TNF) biologicals and case reports published between 2010 and 2014.
Currently approved anti-TNF biologicals in arthritis include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab, and the fusion protein etanercept. The most frequently-reported adverse event was infection. We grouped the adverse reactions as immune-mediated, hypersensitivity syndrome reactions including cutaneous and hepatic manifestation, neurological, hematological, and malignancy.
Most adverse events are due to the failure of host immunological control, which involves susceptibility to the drug itself, or de novo infection or reactivation of a latent bacterial or viral infection, often with a different expression of disease. Drug-induced liver injury associated with anti-TNF biologicals must be kept in mind when evaluating patients with increased liver enzymes.
Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving a personalized medicine approach to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert of anti-TNF agents as potential causes of drug-induced liver injury and monitor the therapies. Personalizing therapeutic pharmacovigilance promises to optimize benefits while minimizing side effects.
In vitro and animals models have long been used to study human diseases and identify novel therapeutic approaches that can be applied to combat these conditions. Ulcerative colitis and Crohn’s ...disease are the two main entities of inflammatory bowel disease (IBD). There is an intricate relationship between IBD features in human patients, in vitro and animal colitis models, mechanisms and possible therapeutic approaches in these models, and strategies that can be extrapolated and applied in humans. Malnutrition, particularly protein-energy malnutrition and vitamin and micronutrient deficiencies, as well as dysregulation of the intestinal microbiota, are common features of IBD. Based on these observations, dietary supplementation with essential nutrients known to be in short supply in the diet in IBD patients and with other molecules believed to provide beneficial anti-inflammatory effects, as well as with probiotic organisms that stimulate immune functions and resistance to infection has been tested in colitis models. Here we review current knowledge on nutritional and probiotic supplementation in in vitro and animal colitis models. While some of these strategies require further fine-tuning before they can be applied in human IBD patients, their intended purpose is to prevent, delay or treat disease symptoms in a non-pharmaceutical manner.
Alcoholic Liver Disease: Role of Cytokines Neuman, Manuela G; Maor, Yaakov; Nanau, Radu M ...
Biomolecules,
08/2015, Letnik:
5, Številka:
3
Journal Article, Book Review
Recenzirano
Odprti dostop
The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical and translational research. It focuses on the role of the immune system and the ...signaling pathways of cytokines in the pathogenesis of ALD. An additional factor that contributes to the pathogenesis of ALD is lipopolysaccharide (LPS), which plays a central role in the induction of steatosis, inflammation, and fibrosis in the liver. LPS derived from the intestinal microbiota enters the portal circulation, and is recognized by macrophages (Kupffer cells) and hepatocytes. In individuals with ALD, excessive levels of LPS in the liver affect immune, parenchymal, and non-immune cells, which in turn release various inflammatory cytokines and recruit neutrophils and other inflammatory cells. In this review, we elucidate the mechanisms by which alcohol contributes to the activation of Kupffer cells and the inflammatory cascade. The role of the stellate cells in fibrogenesis is also discussed.
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