Drug-Induced Nodular Regenerative Hyperplasia

Drug-induced liver disease encompasses a wide range of pathology including idiosyncratic drug-induced liver injury (DILI), acute fatty liver, autoimmune hepatitis, sclerosing cholangitis, granulomatous hepatitis, and nodular regenerative hyperplasia, as well as drug-associated fatty liver disease, cirrhosis, and liver tumours. The vast majority of commonly used drugs are reported to be associated with DILI, including over-the-counter preparations, herbal remedies, and dietary supplements. It is important to consider drug therapy as an aetiology when assessing patients presenting with hepatocellular or cholestatic patterns of liver injury. Systematic evaluation and prompt diagnosis followed by discontinuation of the particular medication is crucial to prevent the development of acute liver failure and to avoid inappropriate investigations. Both candidate gene and genome-wide association studies have identified the critical role of the adaptive immune system in the pathogenesis of idiosyncratic DILI. Human leucocyte antigen alleles that are strongly associated with DILI have the potential to assist in the clinical investigation of patients suspected to have DILI in particular circumstances.

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Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review

Hepatitis Research and Treatment ◽

10.1155/2014/562979 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Shrruti Grover ◽

Archana Rastogi ◽

Jyotsna Singh ◽

Apurba Rajbongshi ◽

Chhagan Bihari

Keyword(s):

Lupus Erythematosus ◽

Vascular Diseases ◽

Nodular Regenerative Hyperplasia ◽

Drug Induced ◽

Collagen Vascular Diseases ◽

Hepatic Involvement ◽

Multisystem Involvement ◽

Clinically Significant ◽

Histopathologic Findings ◽

Portal Tracts

Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts.

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Early Development of Drug-Induced Hepatic Necrosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066942 ◽

1971 ◽

Vol 29 ◽

pp. 576-577

Author(s):

F. G. Zaki ◽

E. Detzi ◽

C. H. Keysser

Keyword(s):

Early Development ◽

Hepatic Necrosis ◽

Screening Tests ◽

Dense Matrix ◽

Sprague Dawley ◽

Electron Microscopic ◽

Drug Induced ◽

Hepatocellular Damage ◽

Sprague Dawley Rats ◽

Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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Effect of piperacillin on morphology and viability of gram-negative bacteria

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111203 ◽

1984 ◽

Vol 42 ◽

pp. 218-219

Author(s):

R. H. Liss

Keyword(s):

Inhibitory Concentration ◽

Cytoplasmic Membrane ◽

Drug Binding ◽

Gram Negative Bacteria ◽

Bacterial Cells ◽

Drug Induced ◽

Penicillin Binding Proteins ◽

Lactam Antibiotic ◽

Drug Free ◽

Tube Dilution

Piperacillip (PIP) is b-[D(-)-α-(4-ethy1-2,3-dioxo-l-piperzinylcar-bonylamino)-α-phenylacetamido]-penicillanate. The broad spectrum semisynthetic β-lactam antibiotic is believed to effect bactericidal activity through its affinity for penicillin-binding proteins (PBPs), enzymes on the bacterial cytoplasmic membrane that control elongation and septation during cell growth and division. The purpose of this study was to correlate penetration and binding of 14C-PIP in bacterial cells with drug-induced lethal changes assessed by microscopic, microbiologic and biochemical methods.The bacteria used were clinical isolates of Escherichia coli and Pseudomonas aeruginosa (Figure 1). Sensitivity to the drug was determined by serial tube dilution in Trypticase Soy Broth (BBL) at an inoculum of 104 organisms/ml; the minimum inhibitory concentration of piperacillin for both bacteria was 1 μg/ml. To assess drug binding to PBPs, the bacteria were incubated with 14C-PIP (5 μg/0.09 μCi/ml); controls, in drug-free medium.

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012895x ◽

1987 ◽

Vol 45 ◽

pp. 934-935

Author(s):

S.S. Poolsawat ◽

C.A. Huerta ◽

S.TY. Lae ◽

G.A. Miranda

Keyword(s):

Cell Proliferation ◽

Liver Function ◽

Chronic Inflammation ◽

Foam Cell ◽

Term Effect ◽

Short Term ◽

Drug Induced ◽

Experimental Induction ◽

Tissue Alterations ◽

Toxic Responses

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

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Drug-Induced Movement Disorders

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld25.2.70 ◽

2015 ◽

Vol 25 (2) ◽

pp. 70-77

Author(s):

Amy Lustig ◽

Cesar Ruiz

Keyword(s):

Movement Disorders ◽

Medical Management ◽

Disease Process ◽

Underlying Disease ◽

Extrapyramidal Symptoms ◽

Drug Induced ◽

General Overview ◽

Management Approaches ◽

Broad Understanding ◽

Underlying Disease Process

The purpose of this article is to present a general overview of the features of drug-induced movement disorders (DIMDs) comprised by Parkinsonism and extrapyramidal symptoms. Speech-language pathologists (SLPs) who work with patients presenting with these issues must have a broad understanding of the underlying disease process. This article will provide a brief introduction to the neuropathophysiology of DIMDs, a discussion of the associated symptomatology, the pharmacology implicated in causing DIMDs, and the medical management approaches currently in use.

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