Manuela G Neuman

In Vitro Drug Safety and Biotechnology

Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and an immune response leading to a hypersensitivity react...

Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a patient was admitted with possible alcoholic hepatitis. The fir...

Alcohol effect hepatic lipid metabolism through various mechanisms, leading synergistically to an accumulation of fatty acids (FA) and triglycerides. Obesity, as well as dietary fat (saturated fatty acids (FA) versus poly-unsaturated fatty acids (PUFA)) may modulate the hepatic fat. Alcohol inhibits adenosine monophosphate activated kinase (AMPK)....

Alcohol effects on hepatic lipid metabolism through various mechanisms, leading synergistically to an accumulation of fatty acids (FA) and triglycerides. Obesity, as well as, the dietary fat [saturated fatty acids (FA) versus poly-unsaturated fatty acids (PUFA)] may modulate the hepatic fat. Alcohol inhibits adenosine monophosphate activated kinase...

In alcohol-induced liver disease (ALD) and in non-alcoholic fatty liver disease (NAFLD), there are abnormal accumulations of fat in the liver. This phenomenon may be related to excessive alcohol consumption, as well as the combination of alcohol consumption and medications. There is an evolution from simple steatosis to steatohepatitis, fibrosis an...

Herbal medicines including teas and plant extracts have been in use for thousands of years. There are reports of the use of herbal preparations in Egypt, China, India, and Samaria. Many patients consider “natural” herbal teas to be completely free of unwanted side effects. Many herbal products, however, have biological activities that can result in...

Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by th...

The present review is based on the research presented at the symposium dedicated to the legacy of the two scientists that made important discovery in the field of alcohol-induced liver damage: Prof C. S. Lieber and Prof. S.W. French. The invited speakers described pharmacological, toxicological and patho-physiological effects of alcohol misuse. Mor...

Hepatitis C virus (HCV)-induced liver disease contributes to chronic hepatitis. The immune factors identified in HCV include changes in the innate and adaptive immune system. The inflammatory mediators, known as “inflammasome”, are a consequence of the metabolic products of cells and commensal or pathogenic bacteria and viruses. The only effective...

Introduction Alcohol-related liver disease (ALD) represents the most common liver disease worldwide, however, the underlying molecular mechanisms are still poorly understood. Namely centrilobular inflammation and programmed cell death are characteristic to ALD and it remains to be elucidated why they persist despite the absence of alcohol. Aims To...

The intestinal microbiome (IM) is important for normal gastrointestinal (GI) and other organ systems’ functioning. An alteration in the normal IM, dysbiosis, and changes in intestinal motility result in microorganisms’ overgrowth and an alteration in intestinal permeability. The gut–brain axis is also of importance in the irritable bowel syndrome (...

This review describes the history of alcoholic liver disease from the beginning of the 1950s until now. It details how the hepatotoxicity of alcohol was discovered by epidemiology and basic research primarily by using new feeding techniques in rodents and primates. The article also recognizes the pioneering work of scientists who contributed to the...

A 52-year-old woman with a BMI of 31.2 kg/m2 was treated with the glucagon-like peptide 1 (GLP-1) agonist liraglutide as part of her weight-reduction program. Following this, she developed an idiosyncratic drug-related liver injury (IDILI). Advances in noninvasive techniques enabled this diagnosis to be established. By employing easily quantifiable...

Uncontrolled immune response to a pathogen or any protein can lead to tissue damage and autoimmune diseases, that represent aberrant immune responses of the individual to its own cells and/or proteins. The immune checkpoint system is the regulatory mechanism that controls immune responses. Tumor cells escape the immune surveillance mechanism, avoid...

Denosumab–Prolia®, Xgeva® (Amgen) is a fully human antibody to the receptor activator of the nuclear factor-K ligand (RANKL). Hepatotoxicity is extremely rare, with only one reported case of immune origin. We present a second case of hepatotoxicity resulting from an immune reaction to denosumab. A 43-year-old female was referred to the Endocrinolog...

Cannabis has been used for its medicinal purposes since ancient times. Its consumption leads to the activation of Cannabis receptors CB1 and CB2 that, through specific mechanisms can lead to modulation and progression of inflammation or repair. The novel findings are linked to the medical use of Cannabis in gastrointestinal (GI) system. Purpose:...

Introduction NAFLD is the hepatic component of the metabolic syndrome, . Although the only proven treatment is weight loss, diet , exercise, and consumption of coffee. Many medications are being investigated for treatment of NAFLD Aim To present different aspects of NAFLD as part of the metabolic syndrome and to review some aspects of obeticholic...

Gamma glutamyl transferase (GGT) is an enzyme in glutathione and cysteine metabolism. GGT is a standard liver enzyme test reflecting biliary tract involvement. It also has a prooxoidant activity and a modulating influence on endothelia dysfunction. GGT is associated with the metabolic syndrome and is often elevated in patients with NAFLD. There is...

The following review article presents clinical and experimental features of alcohol-induced liver disease (ALD). Basic aspects of alcohol metabolism leading to the development of liver hepatotoxicity are discussed. ALD includes fatty liver, acute alcoholic hepatitis with or without liver failure, alcoholic steatohepatitis (ASH) leading to fibrosis...

Toxic liver disease, hepatotoxicity, encompasses numerous different individual diseases that ultimately lead to progressive damage of the liver, to liver malfunction and death. Environmental toxicity, alcoholic and non-alcoholic steatohepatitis, viral hepatitis, and cirrhosis are examples of liver diseases, though not reciprocally exclusive, that c...

Liver injuries caused by the use of exogenous compounds such as drugs, herbs, and alcohol are commonly well diagnosed using laboratory tests, toxin analyses, or eventually reactive intermediates generated during metabolic degradation of the respective chemical in the liver and subject to covalent binding by target proteins. Conditions are somewhat...

Objectives: To systematically summarize the risk relationship between different levels of alcohol consumption and incidence of liver cirrhosis. Methods: MEDLINE and Embase were searched up to March 6, 2019, to identify case-control and cohort studies with sex-specific results and more than 2 categories of drinking in relation to the incidence of...

Drug-induced liver injury (DILI) is a comprehensive phenomenon. The injury to the liver may occur as an unexpected and undesired reaction to a therapeutic dose of a drug (idiosyncratic reaction), or as an expected therapeutic effect of the direct (intrinsic) toxicity of a drug taken in a large enough dose to cause liver injury.The direct toxicity (...

Ayurveda is an ancient Indian medicinal practice. The present review includes translational research characterizing obesity, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). We reviewed published research on improving function through Ayurvedic medicine by searching electronic databases (Medline, Embase) using ter...

Background and aim The non-alcoholic fatty liver disease (NAFLD) and its sub-entity, the non-alcoholic steatohepatitis (NASH) represent a field of a tremendous progress in recent years. Clinicians need to remain updated with new data on pathogenesis and therapy. The present mini review aims to present some new scientific reports on the diagnosis of...

Objectives: (1) to describe a heavy-alcohol user, who was diagnosed with POEMS; (2) to demonstrate the utility of quantitative measurement of serum levels of VEGF in the diagnosis of POEMS and the monitoring of therapeutic interventions; (3) to demonstrate that overproduction of pro-inflammatory cytokines is a characteristic of POEMS. Methods: W...

Objective: Denosumab (Prolia, Amgen, Thousand Oaks, CA, USA) is a fully human antibody to the receptor activator of nuclear factor-KB ligand (RANKL). We present a case of submassive hepatic necrosis with evidence implicating cytokine induction resulting from an immune reaction to denosumab. Case report: A 72-year-old lady presented with elevated...

Objective: Herbal remedies containing pyrrilidozine alkaloids (PA)s can induce liver damage, including hepato-sinusoidal obstruction syndrome (HSOS) or veno-occlusive liver disease (VOD). Some individuals misusing alcohol consume also teas and/or herbal remedies containing PA. The interaction or additive toxicity of alcohol to PA toxicity needs to...

This paper is based upon the “8th Charles Lieber's Satellite Symposium” organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA.

We thank Lonardo et al. (2016) for their comments on our meta-analysis on the relationship between alcohol consumption and hepatic steatosis (Roerecke et al., 2016). We would like to clarify our position on overall risk associated with alcohol consumption and specifically on the risk of hepatic steatosis. First, as we have stated in our paper, we a...

Supplementary material.

Background: Fatty liver (hepatic steatosis) is one of the most common diseases globally, with increasing prevalence. The role of alcohol consumption in the development of hepatic steatosis has not been systematically examined. Methods: We searched Medline, Embase, and ProQuest Dissertations & Theses Global for original data on the relationship b...

Non-alcoholic fatty liver disease; Meta-analysis

Unlabelled: The present review includes translational and clinical research that characterize non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Clinical and experimental evidence led to the recognition of the key toxic role played by lipotoxicity in the pathogenesis of NAFLD. The current understanding of lipotoxic...

Purpose: 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. Design and methods:...

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), w...

The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical research, translational research, pathogenesis and therapies. A special accent is placed on alcohol misuse, as alcohol is a legally commercialized and taxable product. Drinking alcohol, particularly from a young age, is a major health...

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 rec...

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 misc...

Unhealthy diet and lack of physical exercise are responsible for fat accumulation in the liver, which may lead to liver disease. Histologically, the severity of the disease has two stages: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD is defined by the presence of steatosis with no evidence of cellular inju...

Quinolones are intensively used, broad spectrum antibiotics that can induce immediate- and delayed-type hypersensitivity reactions, either IgE or T-cell mediated, in about 2-3% of treated patients. To better understand how T cells interact with quinolones, to produce the hypersensitivity and to describe the possible prevention of the reactions. We...

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 necrosi...

Non-alcoholic fatty liver disease (NAFLD) is by far the most common form of chronic liver disease worldwide, affecting adults as well as children. Under the term of NAFLD there is a wide spectrum of diseases ranging from simple steatosis to the non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC)....

Background: 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 i...

Background: Biological therapies using anti-tumor necrosis factor (TNF)-α agents have an important impact in the treatment of inflammatory bowel disease, rheumatoid arthritis, psoriasis, and other inflammatory conditions. However, a significant number of patients lose their response to these medications over time. Clinical trials have demonstrated...

Purpose: 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 freq...

This paper is based upon the 'Charles Lieber Satellite Symposia' organized by Manuela G. Neuman at each of the 2009-2012 Research Society on Alcoholism (RSA) Annual Meetings. The presentations represent a broad spectrum dealing with alcoholic liver disease (ALD). In addition, a literature search (2008-2013) in the discussed area was performed in or...

Ischemic heart disease is the primary cause of death worldwide. The pathophysiological process of cardiovascular diseases is linked to atheromatous plaque formation, while plaque rupture releases thrombogenic elements, which lead to activation of platelets, blood clotting and formation of thrombi. Platelet inhibitors are used to prevent thrombosis....

Inflammatory bowel disease, including its 2 entities ulcerative colitis and Crohn's disease, is a chronic medical condition characterized by the destructive inflammation of the intestinal tract. Biologics represent a class of therapeutics with immune intervention potential. These agents block the proinflammatory cascade that triggers the activation...

Serum tumour necrosis factor-alpha (TNF-α) levels correlate negatively with hepatitis C virus (HCV) antiviral response. OBJECTIVES: To test the hypothesis that a single infliximab induction dose would positively influence on-treatment virological response and sustained virological response (SVR). METHODS: The present study was a phase IIIB, randomi...

To determine the cytotoxicity of valproic acid (VPA) and its derivatives in human hepatoblastoma cells (HepG2), and to study the possible toxicity of these compounds in human lymphocytes from patients with known hypersensitivity syndrome reactions (HSR) to other medication. Cells were exposed to physiological doses of VPA, valnoctamide (VCD) and it...

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 pol...

Background: Herbal-induced injury to the liver is a many-faceted phenomenon. The diverse aspects include the nature of the hepatotoxic agents, the character of the injury, the mechanism for the hepatotoxic effects, the circumstances of exposure, and the medical and social importance. Purpose: The objectives are to encourage recognition and preventi...

Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to...

Ischemic heart disease is the second leading cause of death in developing countries. The proportion of deaths resulting from this condition has decreased in the last two decades, mainly as a result of improved primary and secondary prevention of cardiovascular events, as well as the development of patient awareness and medical and pharmacological m...

Ibuprofen is a non-selective non-steroidal anti-inflammatory drug widely used for the treatment of fever, inflammation and pain. The present paper reviews the main types of adverse drug reactions (ADR) associated with ibuprofen, while briefly touching on the similarities and differences between ibuprofen ADRs and selective cyclooxygenase-2 inhibito...

Inflammatory bowel disease (IBD) encompasses several chronic inflammatory disorders leading to the damage of the gastrointestinal tract. The 2 principal forms of these disorders are ulcerative colitis (UC) and Crohn's disease (CD). Bacteria are involved in the etiology of IBD. Many microorganisms have been put forward as causative factors in IBD, b...

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 fact...

Strong evidence indicates that inflammatory bowel disease, including Crohn disease and ulcerative colitis, is a result of an inappropriate inflammatory response in which genetic and environmental factors play important roles. This review discusses several single-nucleotide polymorphisms with either susceptibility or protective effects on inflammato...

Background: Alcohol plays a role at the different points in the natural history of HIV/AIDS: This article focuses on the health implications of harmful alcohol consumption in the era of antiretroviral therapy. Aim: To explore the role of alcohol in HIV disease progression, in order to improve HIV patient management and overall better HIV prognosis....

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 an...

Many countries with heavy HIV and alcohol burdens do not fully recognize these epidemics as intrinsically interconnected. Missed opportunities for synergistic prevention and treatment of HIV and alcohol abound.Few HIV policies, services for HIV prevention or research projects adequately address alcohol-HIV harms or include alcohol use as an HIV ris...

Background. There are challenges in the clinical diagnosis of drug-induced injury and in obtaining information on the reactivation of human herpes viruses (HHV) during idiosyncratic adverse drug reactions. Objectives. (i) To develop a unified list of drugs incriminated in drug-induced hepatotoxicity and severe cutaneous reactions, in which drug hyp...

Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR). We aimed (1) to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically; (2) to correlate LTA results with the clinical syndrome; (3) to correlate LT...

The present paper describes the possible connection between alcohol consumption and adherence to medicine used to treat human deficiency viral (HIV) infection. Highly active antiretroviral therapy (HAART) has a positive influence on longevity in patients with HIV, substantially reducing morbidity and mortality, including resource-poor settings such...

The present paper describes possible connections between antiretroviral therapies (ARTs) used to treat human immunodeficiency virus (HIV) infection and adverse drug reactions (ADRs) encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly...

High levels of profibrinogenic cytokine transforming factor beta (TGF-β), metalloprotease (MMP2), and tissue inhibitor of matrix metalloprotease 1 (TIMP1) contribute to fibrogenesis in hepatitis C virus (HCV) infection and in alcohol-induced liver disease (ALD). The aim of our study was to correlate noninvasive serum markers in ALD and HCV patients...

Ischemic heart disease is the second leading cause of death in the world. The proportion of deaths resulting from this condition has decreased in the last two decades, mainly as a result of improved primary and secondary prevention of cardiovascular events, as well as the development of patient awareness and medical and pharmacological management....

Enabled by Pharmacogenomics (PGx), molecular imaging, and other molecular biomarkers, personalized medicine (PM) promises to optimize therapy while minimizing side effects. It may also dramatically impact the justice system in ways we are only beginning to understand. KeywordsPersonalized justice-Daubert standard

Hypersensitivity syndrome reactions (HSR) to antiepileptic drugs (AED) are associated with severe clinical cutaneous adverse reactions (SCAR).Our aims are: to assess HSRs to AEDs using the in vitro lymphocyte toxicity assay (LTA) in patients who manifested HSRs clinically, to correlate LTA results with the clinical syndrome, to correlate LTA result...