Herbal remedies and health foods are widely used, and their side effects have been reported. We describe two cases of symptomatic toxic hepatitis that developed in middle-aged women after ingesting arrowroot juice. The clinical manifestations were nausea, vomiting, and jaundice. The diagnosis of toxic hepatitis was made using the Roussel Uclaf Causality Assessment Method score on the basis of the patient's history and laboratory data. After supportive care, the patients showed rapid improvements of clinical symptoms, laboratory findings, and liver stiffness. Clinicians should be aware that the consumption of arrowroot juice can cause toxic hepatitis.
Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Drug-Induced Liver Injury/complications/*diagnosis/ultrasonography ; Elasticity Imaging Techniques ; Exanthema/complications ; Female ; Humans ; Marantaceae/*chemistry ; Middle Aged ; Plant Extracts/*toxicity

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (P(enh)) was measured. Levels of IL-4 and IFN-gamma were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher P(enh) than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-gamma were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-gamma suggesting that DEP amplify Th2 immune response.
Air Pollutants, Environmental/toxicity ; Animals ; Asthma/*chemically induced/*immunology ; Disease Models, Animal ; Drug Combinations ; Drug Synergism ; Female ; Hypersensitivity/complications/*etiology/*immunology ; Interferon Type II/immunology ; Interleukin-4/immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Ozone/*toxicity ; Pneumonia/*chemically induced/complications/*immunology ; Research Support, Non-U.S. Gov't ; Respiratory Hypersensitivity/chemically induced/complications/immunology ; Vehicle Emissions/*toxicity

The detection of sperm DNA damage, as an important supplement to semen routine examination strategies, has been applied in some clinical andrology laboratories. What factors may lead to sperm DNA damage remains one of the concerns among many andrologists. Present studies show a variety of factors of sperm DNA damage, including age, environmental pollutants such as organophosphorus and organochloride pesticides, plasticizer, heavy metals such as lead, carcinogens such as polycyclic aromatic hydrocarbons (c-PAHs) and zearalenone (ZEA), male reproductive system diseases or systemic diseases such as varicocele, infection, tumor, spermatogenesis and maturation dysfunction, spinal cord injury and endocrine disorders, seasons and temperature, lifestyle, abstinence time, semen refrigeration, semen handling in vitro, and certain medications. Among them, spermatogenesis and sperm maturation dysfunction may be the most secretive factors, which are involved in the molecular mechanisms of sperm chromatin packaging and restructuring, such as the transformation of histone to protamine, single nucleotide polymorphism of genes, and the role of telomere, which may be one of the hotspots in the future studies of sperm DNA damage. Relevant researches in the future are expected to focus on the prevention of sperm DNA damage and clarification of its specific pathogenic mechanisms so as to provide some evidence for its treatment.
Age Factors ; Chromatin ; chemistry ; DNA Damage ; Environmental Pollutants ; toxicity ; Humans ; Male ; Protamines ; Semen ; drug effects ; Specimen Handling ; Spermatogenesis ; Spermatozoa ; drug effects ; Telomere ; physiology ; Varicocele ; complications

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity. A 37-year-old female with gastric cancer underwent a curative operation, followed by adjuvant chemotherapy consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level was lower than that in a control group. Thus, when considering the routine use of 5-FU for the treatment of cancer patients, an analysis of DPD activity or screening for DPD mutations is warranted in confined patients who experience unpredicted severe toxicity after initial 5-FU administration, even though DPD deficiency is a rare metabolic defect.
Stomach Neoplasms/complications/*drug therapy/surgery ; Risk Factors ; Risk Assessment ; Humans ; Fluorouracil/*adverse effects ; Female ; *Drug Toxicity ; Dihydrouracil Dehydrogenase (NADP)/*deficiency ; Chemotherapy, Adjuvant ; Antimetabolites, Antineoplastic/*adverse effects ; Adult ; Adenocarcinoma/complications/*drug therapy/surgery

OBJECTIVENumerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid (3-NP) intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP.

METHODSMouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test.

RESULTS(1) On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. (2) In the following Y-maze test after 1h interval, the percentage (90.0%) of mice showing novel arm preference in 3-NP treatment group was significantly higher than the random chance level (50%), although it was only slightly higher than that (83.3%) in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. (3) For both post-intoxicated (on day 15 and day 45 following 3-NP treatment) and control groups, the duration in the novel arm and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test.

CONCLUSIONKunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.

Animals ; Behavior, Animal ; Convulsants ; toxicity ; Male ; Maze Learning ; drug effects ; Memory Disorders ; etiology ; Mice ; Mice, Inbred Strains ; Motor Activity ; drug effects ; Movement Disorders ; etiology ; Nitro Compounds ; toxicity ; Poisoning ; complications ; etiology ; Propionates ; toxicity ; Recovery of Function ; drug effects ; physiology ; Rotarod Performance Test ; Time Factors

OBJECTIVEWe tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo).

METHODSRats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition.

RESULTSNephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones.

CONCLUSIONOur findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.

Animals ; Disease Models, Animal ; Hyperuricemia ; chemically induced ; complications ; Kidney Diseases ; chemically induced ; Lipid Peroxidation ; drug effects ; Male ; Oxonic Acid ; Rats, Wistar ; Triazines ; toxicity

To explore the underlying mechanism(s) of pulmonary arterial hypertension in endotoxic shock, the roles of N-acetylcysteine (NAC), nitric oxide (NO) and carbon monoxide (CO) were investigated. Pulmonary arterial rings (3-mm width) were prepared from 24 rabbits. Lipopolysaccharide (LPS), after 7-hour incubation, decreased the endothelium-dependent relaxation response of the arterial ring (pre-contracted with phenylephrine) to acetylcholine (1 mumol/L), but did not affect the endothelium-independent relaxation response to sodium nitroprusside. The LPS effects were reduced by a concomitant incubation with the free radical scavenger (NAC), NO donor (L-arginine), and CO donor (hemin), respectively. On the other hand, the LPS effects were enhanced by applying heme oxygenase-1 (HO-1) inhibitor (zinc protoporphyrin) to block CO production. The response to acetylcholine changed from relaxation to contraction, however, the contractile response to phenylephrine increased significantly after pre-incubation with nitric oxide synthase (NOS) inhibitor (L-NAME) to block NO production, confirming the importance of CO and NO. These results show that LPS impairs endothelium-dependent relaxation of the pulmonary artery, which can be greatly reduced by the antioxidant, or by supplying with NO and CO. Thus, multiple factors are involved in this model of endotoxin-induced pulmonary hypertension.
Acetylcysteine ; metabolism ; Animals ; Carbon Monoxide ; metabolism ; Hypertension, Pulmonary ; etiology ; physiopathology ; Lipopolysaccharides ; toxicity ; Male ; Nitric Oxide ; metabolism ; Pulmonary Artery ; drug effects ; physiopathology ; Rabbits ; Shock, Septic ; complications

Animals ; Brain ; drug effects ; pathology ; physiology ; Child ; Child Development ; drug effects ; Female ; Fetus ; drug effects ; Humans ; Hypothalamo-Hypophyseal System ; physiology ; Metals ; toxicity ; Pituitary-Adrenal System ; physiology ; Pregnancy ; Stress, Psychological ; complications

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
Acetamides ; therapeutic use ; Animals ; Chemokine CXCL10 ; metabolism ; Chloroquine ; toxicity ; Chronic Disease ; Cyclopropanes ; adverse effects ; Dehydration ; complications ; Dinitrofluorobenzene ; adverse effects ; Disease Models, Animal ; Formaldehyde ; toxicity ; Freund's Adjuvant ; toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; drug effects ; Pain ; chemically induced ; Pruritus ; chemically induced ; pathology ; Pyrimidines ; therapeutic use ; Receptors, CXCR3 ; antagonists & inhibitors ; genetics ; metabolism ; Skin ; pathology ; Spinal Cord ; drug effects ; metabolism ; pathology ; Time Factors ; p-Methoxy-N-methylphenethylamine ; toxicity

OBJECTIVES: We evaluated the risk of fracture associated with hypotension-related adverse drug reaction caused by taking alpha blockers to treat benign prostatic hyperplasia (BPH). METHODS: We used the Health Insurance Review and Assessment Service database from January 1st 2005 to June 30th 2006 for this study. The male patients with BPH and who had a prescription for alpha blockers following any fractures were defined as the cases. We set the 20 day long hazard period prior to the index date and the four control periods whose lengths were same with hazard period. After 1:4 matching of the hazard and control periods, conditional logistic regression was used to calculate the odds ratios for the risk of fractures as related to the alpha blocker exposure. RESULTS: Doxazosin and tamsulosin showed the increased risk of fractures, whereas terazosin did not. After stratification using the defined daily doses, a protective effect was shown for the patients who took terazosin at the doses lower than 0.4 DDD and the hazardous effect at the doses higher than or equal to 0.4 DDD. There was no significant difference for the risk of patients taking tamsulosin at the doses higher than 1.0 DDD but there was a statistically significant increase in the risk at the doses higher than or equal to 1.0 DDD. CONCLUSIONS: Alpha blockers for BPH may increase the risk of fracture in elderly patients who have comorbidities and take the concomitant medications. Alpha blockers need to be prescribed with caution, although some have high prostate specificity.
Adrenergic alpha-Antagonists/*therapeutic use ; Aged ; Aged, 80 and over ; Cross-Over Studies ; Drug Toxicity/complications ; Fractures, Bone/*chemically induced/epidemiology ; Humans ; Korea/epidemiology ; Male ; Prostatic Hyperplasia/*drug therapy ; Risk Assessment