Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The effects of vitamin E and catechin

Doxorubicin (DXR) is an anthracycline antibiotic, broadly used in tumor therapy. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of doxorubicin. Vitamin E (200 IU/kg/week), catechin (200 mg/kg/week), doxorubicin (5 mg/kg/week), doxorubicin+vitamin E (200 IU/kg/week), doxorubicin+catechin (200 mg/kg/week) combinations were given to rats weighing 210-230 g (n=6/group). Changes in major enzymes participating in free radical metabolism superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSHPx), catalase (CAT) and malondialdehyde (MDA) were evaluated in the livers of all animals. Superoxide dismutase and catalase activity increased in the doxorubicin-treated group compared to control (P<0.05). Glutathione peroxidase levels increased in the catechin+doxorubicin-treated group (P<0.05) and reached maximum concentrations in the doxorubicin-treated group compared to control (P<0.01). Malondialdehyde levels increased in the doxorubicin-treated group compared to control and all-treated groups (P<0.05). Malondialdehyde, glutathione peroxidase and catalase activities were decreased in the vitamin E+doxorubicin- and catechin+doxorubicin-treated group compared to doxorubicin-treated group (P<0.05). All enzymes activities showed no statistical differences in the not mentioned groups above (P>0.05). Electron microscopic studies supported biochemical findings. We conclude that vitamin E and catechin significantly reduce doxorubicin-induced hepatotoxicity in rats.     

Impaired antioxidant defence in guinea pig heart tissues treated with halothane

Purpose

To investigate the effects of halothane and halothane plus vitamin E treatment on myocardial free radical metabolism in guinea pigs.

Methods

Four groups of seven animals were studied; control, halothane, halothane plus vitamin E and vitamin E groups. In the halothane group, halothane 1.5% in oxygen was given for 90 min over three days. In the halothane plus vitamin E group, 300 rng · kg^?1 · day^?1 vitamin Eim was started three days before the first halothane treatment and continued for three days. Following sacrifice, the hearts were assayed for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and malondialdehyde (MDA) level was determined. Electron spin resonance (ESR) analysis and electron microscopy (EM) were also performed.

Results

In the halothane group, SOD activities and MDA concentrations were increased compared with control and GSH-Px and CAT activities were decreased. In the halothane plus vitamin E group, there were no differences in enzyme activity compared with halothane alone but the MDA level was decreased. In the vitamin E group, enzyme activities were increased compared with control. Mainly the CF₃CHCl radical was identified by ESR analysis in heart tissues exposed to halothane and the concentration of this radical was reduced by vitamin E. Electron microscopy showed cytoplasmic vacuolisation and dilation in sarcoplasmic reticulum in the heart tissues exposed to halothane: both were prevented by vitamin E.

Conclusion

Although halothane causes impairment in enzymatic antioxidant defence potential, due to lowered GSH-Px and CAT activity, and accelerates peroxidative reactions in the tissues affected, no subcellular damage occurred. Vitamin E may protect tissues against free radical attack by scavenging toxic free radicals formed in heart tissue during halothane anaesthesia.     

Efficacy,Safety, and Pharmacokinetics of a Novel Human Immune Globulin Subcutaneous, 20 % in Patients with Primary Immunodeficiency Diseases in North America

Patients with primary immunodeficiency disease (PIDD) typically require life-long intravenous (IV) or subcutaneous (SC) immunoglobulin (Ig) replacement therapy to prevent recurrent infections. The efficacy, safety, and pharmacokinetics of a highly concentrated (20 %) Ig preparation for SC administration (IGSC 20 %) were evaluated in a prospective trial in patients with PIDD. A total of 74 patients (aged 3–83 years) received 4327 IGSC 20 % infusions over a median of 380.5 days. The rate of validated serious bacterial infections was 0.012 event/patient-year (p?<?0.0001 compared with the historical control), and the annualized rate of infection was 2.41 events/patient. Median IgG trough levels were >14.5 g/l. The median maximum infusion rate was 60 ml/h/site (range 4.4–180), resulting in a median infusion duration of 0.95 h. A volume ≥30 ml was infused per site in 74.8 % of IGSC 20 % infusions. Most (84.9 %) infusions were administered using ≤2 infusion sites; for 99.8 % of infusions, there was no need to interrupt/stop administration or reduce the infusion rate. No related serious adverse event (AE) occurred during IGSC 20 % treatment; related non-serious AEs occurred at a rate of 0.036 event/infusion. The incidence of related local AEs was 0.015 event/infusion and of related systemic AEs was 0.021 event/infusion; most were mild in severity, none severe. Increased infusion rates or volumes were not associated with higher AE rates. The investigated IGSC 20 % treatment was shown to be effective and safe, enabling higher infusion rates and volumes per site compared to conventional SC treatments, resulting in fewer infusion sites and shorter infusion durations.     

Dynamics of circulating microparticles in chronic kidney disease and transplantation:Is it really reliable marker?

The deterioration of endothelial structure plays a very important role in the development of vascular diseases. It is believed that endothelial dysfunction starts in the early stage of kidney disease and is a risk factor of an unfavorable cardiovascular prognosis. Because a direct assessment of biological states in endothelial cells is not applicable, the measurement of endothelial microparticles(EMPs) detached from endothelium during activation or apoptosis is thought to be a marker of early vascular disease and endothelial dysfunction in children with chronic kidney disease(CKD). Few studies have shown increased circulating EMPs and its relationship with cardiovascular risk factors in patients with CKD.MPs contain membrane proteins and cytosolic material derived from the cell from which they originate. EMPs having CD144, CD 146, CD31+/CD41-, CD51 and CD105 may be used to evaluate the vascular endothelial cell damage and determine asymptomatic patients who might be at higher risk of developing cardiovascular disease in CKD and renal transplant.     

Selective IgA Deficiency

Introduction  

Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations.     

Severe T- and B-cell immune deficiency associated with malignant thymoma.

BACKGROUND: Immunodeficiency with thymoma syndrome is a rare disorder that generally occurs after the fourth decade of life. Typically, thymic tumors are benign, and gradually developing immunodeficiency consists of hypogammaglobulinemia with low B-cell counts and an inverted CD4+/CD8+ T-cell ratio due to excessive CD8+ T cells. OBJECTIVE: To report the case of a 32-year-old, white man with an invasive malignant thymoma and profound combined T- and B-cell immunodeficiency associated with a normal CD4+/CD8+ T-cell ratio, absence of circulating B cells, and infection with an unusual organism. METHODS: The patient presented with a superior vena cava syndrome caused by a malignant thymoma. During chemotherapy and radiotherapy, he experienced recurrent episodes of pulmonary infections due to Haemophilus influenza and Serratia marcescens and persistent oral thrush. He was diagnosed as having thymoma and underwent immunological evaluation. RESULTS: Sixteen months after the diagnosis of thymoma, the immunological evaluation revealed profound lymphopenia, eosinopenia, very low counts of both CD4+ T cells and CD8+ T cells, and a normal CD4+/CD8+ ratio with negative delayed-type hypersensitivity skin test results. Hypogammaglobulinemia and absent specific antibody responses were associated with a lack of peripheral blood CD19+ B cells. Despite treatment with intravenous immunoglobulin, the patient died of respiratory insufficiency and sepsis secondary to a chronic pulmonary infection. CONCLUSIONS: Malignant thymoma may be associated with severe combined immunodeficiency. A normal CD4+/CD8+ ratio and the absence of peripheral B cells suggest a bone marrow defect that affects both T and B cells in the pathogenesis of this syndrome. Comprehensive immunological evaluation should be performed when thymoma is diagnosed to initiate an early and effective treatment to prevent life-threatening complications.     

Single-energy pediatric chest computed tomography with spectral filtration at 100 kVp: effects on radiation parameters and image quality

Background

Most of the applied radiation dose at CT is in the lower photon energy range, which is of limited diagnostic importance.

Objective

To investigate image quality and effects on radiation parameters of 100-kVp spectral filtration single-energy chest CT using a tin-filter at third-generation dual-source CT in comparison to standard 100-kVp chest CT.

Materials and methods

Thirty-three children referred for a non-contrast chest CT performed on a third-generation dual-source CT scanner were examined at 100 kVp with a dedicated tin filter with a tube current–time product resulting in standard protocol dose. We compared resulting images with images from children examined using standard single-source chest CT at 100 kVp. We assessed objective and subjective image quality and compared radiation dose parameters.

Results

Radiation dose was comparable for children 5 years old and younger, and it was moderately decreased for older children when using spectral filtration (P=0.006). Effective tube current increased significantly (P=0.0001) with spectral filtration, up to a factor of 10. Signal-to-noise ratio and image noise were similar for both examination techniques (P≥0.06). Subjective image quality showed no significant differences (P≥0.2).

Conclusion

Using 100-kVp spectral filtration chest CT in children by means of a tube-based tin-filter on a third-generation dual-source CT scanner increases effective tube current up to a factor of 10 to provide similar image quality at equivalent dose compared to standard single-source CT without spectral filtration.

     

Diabetic Ketoacidosis Presenting with Pseudonormoglycemia in a 15-Year-Old Girl with Type 1 Diabetes Mellitus

Pseudonormoglycemic diabetic ketoacidosis (DKA) is a rare condition and has been reported only in a few adult patients. We present a 15-year-old girl with a 9-year history of type 1 diabetes who presented with euglycemic and extreme hypertriglyceridemia. The acidosis and hypertriglyceridemia resolved with intravenous insulin therapy and rehydration. Hyperlipidemia was the apparent cause of pseudonormoglycemia in this patient. The findings in the present case demonstrate that also in children, DKA can rarely occur without abnormal blood glucose levels. Assessment of the acid-base status, urinary glucose, and ketone readings is therefore important in all diabetic patients who are unwell at admission and have normal glucose levels. In such patients, hyperlipidemia may cause pseudonormoglycemia. An awareness of this rare treatable life-threatening condition is important. Conflict of interest:None declared.     

Association between Promoter Polymorphisms of TFF1, TFF2, and TFF3 and the Risk of Gastric and Diffuse Gastric Cancers in a Korean Population

Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.

Graphical Abstract

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