Effects of Carbon Monoxide on the Vulnerability of the Ventricles to Drug-Induced Arrhythmias

A 70-year-old man was referred to our respiratory department with non-productive cough over the past 6 months. High-resolution CT revealed reticular pattern with basal and peripheral predominance, centrilobular nodules and mild ground glass opacities. Serology tests were normal and bronchoalveolar lavage revealed lymphocytosis. Pulmonary function tests showed functional impairment and reduced diffusing capacity for carbon monoxide. Meticulous evaluation of patient’s medical history unveiled longitudinal administration of infliximab due to diagnosis of psoriasis. The working diagnosis of drug-induced interstitial lung disease was proposed following multidisciplinary discussion. Considerable radiological and functional improvement was determined 6 months following infliximab discontinuation without implementation of corticosteroids. To this end, the patient has reported remission of cough and functional improvement.

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Evidence for Cytoprotective Effect of Carbon Monoxide Donor in the Development of Acute Esophagitis Leading to Acute Esophageal Epithelium Lesions

Cells ◽

10.3390/cells9051203 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1203 ◽

Cited By ~ 1

Author(s):

Katarzyna Magierowska ◽

Dominik Bakalarz ◽

Dagmara Wójcik ◽

Edyta Korbut ◽

Aleksandra Danielak ◽

...

Keyword(s):

Carbon Monoxide ◽

Sensory Nerve ◽

Cytokine Signaling ◽

Zinc Protoporphyrin ◽

Esophageal Mucosa ◽

Annexin A1 ◽

Esophageal Epithelium ◽

Drug Induced ◽

Mucus Production ◽

Socs3 Mrna

Exposure to acidic gastric content due to malfunction of lower esophageal sphincter leads to acute reflux esophagitis (RE) leading to disruption of esophageal epithelial cells. Carbon monoxide (CO) produced by heme oxygenase (HMOX) activity or released from its donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) was reported to protect gastric mucosa against acid-dependent non-steroidal anti-inflammatory drug-induced damage. Thus, we aimed to investigate if CO affects RE-induced esophageal epithelium lesions development. RE induced in Wistar rats by the ligation of a junction between pylorus and forestomach were pretreated i.g. with vehicle CORM-2; RuCl3; zinc protoporphyrin IX, or hemin. CORM-2 was combined with NG-nitro-L-arginine (L-NNA), indomethacin, capsazepine, or capsaicin-induced sensory nerve ablation. Esophageal lesion score (ELS), esophageal blood flow (EBF), and mucus production were determined by planimetry, laser flowmetry, histology. Esophageal Nrf-2, HMOXs, COXs, NOSs, TNF-α and its receptor, IL-1 family and IL-1 receptor antagonist (RA), NF-κB, HIF-1α, annexin-A1, suppressor of cytokine signaling (SOCS3), TRPV1, c-Jun, c-Fos mRNA/protein expressions, PGE2, 8-hydroxy-deoxyguanozine (8-OHdG) and serum COHb, TGF-β1, TGF-β2, IL-1β, and IL-6 content were assessed by PCR, immunoblotting, immunohistochemistry, gas chromatography, ELISA or Luminex platform. Hemin or CORM-2 alone or combined with L-NNA or indomethacin decreased ELS. Capsazepine or capsaicin-induced denervation reversed CORM-2 effects. COHb blood content, esophageal HMOX-1, Nrf-2, TRPV1 protein, annexin-A1, HIF-1α, IL-1 family, NF-κB, c-Jun, c-Fos, SOCS3 mRNA expressions, and 8-OHdG levels were elevated while PGE2 concentration was decreased after RE. CO donor-maintained elevated mucosal TRPV1 protein, HIF-1 α, annexin-A1, IL-1RA, SOCS3 mRNA expression, or TGF-β serum content, decreasing 8-OHdG level, and particular inflammatory markers expression/concentration. CORM-2 and Nrf-2/HMOX-1/CO pathway prevent esophageal mucosa against RE-induced lesions, DNA oxidation, and inflammatory response involving HIF-1α, annexin-A1, SOCS3, IL-1RA, TGF-β-modulated pathways. Esophagoprotective and hyperemic CO effects are in part mediated by afferent sensory neurons and TRPV1 receptors activity with questionable COX/PGE2 or NO/NOS systems involvement.

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Early-Onset Diagnosis of Lung Toxicity Caused by Cyclophosphamide, Melphalan and Procarbazine Therapy

Tumori Journal ◽

10.1177/030089168707300406 ◽

1987 ◽

Vol 73 (4) ◽

pp. 351-358 ◽

Cited By ~ 3

Author(s):

Vito Michele Lauta ◽

Giuseppe Valerio ◽

Anna Greco ◽

Marino Capece Minutolo

Keyword(s):

Multiple Myeloma ◽

Carbon Monoxide ◽

Lung Function ◽

Lung Toxicity ◽

Small Airways ◽

Lung Function Tests ◽

Diffusing Capacity ◽

Drug Induced ◽

Function Tests ◽

Impaired Lung Function

Lung function studis were performed in 33 patients with lymphomyeloproliferative diseases (25 cases of multiple myeloma and 8 cases of Hodgkin's disease) who received cyclophosphamide, procarbazine, and melphalan therapy. Lung function was investigated by spirometric tests, indicative tests of small airways disease, and diffusing capacity of the lung for carbon monoxide (DUCO). Indicative tests of small airways disease and other lung function tests such as forced expiratory volume in 1 second (FEY,), vital capacity (VC), total lung capacity (TLC) etc. were markedly improved in 18 patients (55%), whereas 24 patients (73%) showed a decreased diffusing capacity of the lung for carbon monoxide. Furthermore, most of the patients (77% – 83%) showed contemporaneous involvement of spirometric tests and DUCO. The DUCO was also found more constantly impaired than other function tests because it had decreased with and without other spirometric tests. Impaired lung function tests were found to be related to a cumulative dose of antineoplastic drugs. The absence of increased lung toxicity was found to be related to several drugs administered in combination. In view of the absence of previous bronchopathies, lung involvement signs in multiple myeloma (25, 26) or lymphoma, and concomitant bronchopneumonias, the impaired functional tests could be ascibed to drug-induced lung toxicity. In the absence of clinical symptoms, roentgenographic and pathologic features, impaired lung function tests may play a role as early-onset signs of drug-induced lung toxicity.

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Regional Cerebral Blood Flow after Marijuana Smoking

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.106 ◽

1992 ◽

Vol 12 (5) ◽

pp. 750-758 ◽

Cited By ~ 76

Author(s):

Roy J. Mathew ◽

William H. Wilson ◽

Diane F. Humphreys ◽

Joe V. Lowe ◽

Kathryn E. Wiethe

Keyword(s):

Carbon Monoxide ◽

Pulse Rate ◽

Plasma Levels ◽

Rating Scales ◽

Right Hemisphere ◽

Previous History ◽

Inhalation Technique ◽

Drug Induced ◽

End Tidal ◽

Smoking Marijuana

Regional CBF was measured with the 133Xe inhalation technique before and thrice after smoking marijuana of two strengths and placebo in 20 physically and mentally healthy male volunteers with a previous history of exposure to marijuana. They were drug-free at the time of the study. Blood pressure, pulse rate, end-tidal carbon dioxide, end-tidal carbon monoxide, and forehead skin perfusion were quantified during the CBF measurements. Blood samples were drawn for quantification of plasma levels of Δ9-tetrahydrocannabinol (THC) before and during the 2 h after smoking marijuana or placebo. Drug-induced intoxication and changes in mood were quantified with rating scales. Marijuana smoking was associated with bilateral CBF increase, which was maximal 30 min later. Greater CBF increases were seen in the frontal region and right hemisphere. No significant CBF changes were seen after placebo. Pulse rate and respiration increased significantly after marijuana but not placebo. Both marijuana and placebo smoking were associated with increased end-tidal carbon monoxide. CBF increase in both hemispheres correlated significantly with degree of intoxication, plasma levels of THC, and pulse rate.

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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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