Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

The effect of nadroparine on coagulation mechanisms: ultrastructural analysis.

Low molecular weight heparins are widely used in the prophylaxis and treatment of thrombotic disorders. The effect of low molecular weight heparins on coagulation was examined ultrastructurally in an animal model. A test and a control group was formed, each consisting of five rabbits. Nadroparine (225 Institute of Chaoy Unit/kg twice daily) was applied to the test group for 10 days. The control group received 1 ml saline solution subcutaneously. Blood and vascular tissue samples collected at the end of the 10th day were evaluated under a JEM 100 B electron microscope. Platelet degranulation and agglutination was observed in the control group. Fibrin materials were detected in the cytoplasms and surroundings of degranulated platelets. Erythrocyte accumulation was remarkable on the vascular endothelium with intact coagulation periods. In the test group, outer membranes of platelets, hyalomere, and granular structures in the granulomeres were detected to be nearly intact. There were rare erythrocytes in the large vascular lumens. The aggregation phase had occurred but no agglutination was detected. Nadroparine seems to preserve consistency of lipoprotein membranes of platelets and granular structures containing enzymes, which contribute to the coagulation mechanisms.     

Peripheral Vascular Complication from Coronary Angiography: a Case Report of Cholesterol Embolization

A 65-year-old man developed acute limb ischemia, severe abdominal wall and lower limb livedo reticularis following a coronary angiogram. The differential diagnoses of acute limb ischemia and multiple cholesterol emboli syndrome (MCES) are discussed. This work was performed at Long Island Jewish Medical Center, 270-05, 76^th Avenue, New Hyde Park, NY 11040.     

Sentinel health events surveillance in diabetes. Deaths among persons under age 45 with diabetes

The pilot study for a sentinel health events surveillance system for deaths among persons under age 45 with diabetes was conducted in six states in 1984 and 1985. Two hundred and thirty-three events were identified. Information from death certificates, physicians, and families revealed that 22% died from acute complications of diabetes and 53% from chronic complications. Blood pressure measurement and urinalysis testing had been performed in the last year for almost all of the decedents, but other preventive practices were reported less frequently. Hypertension was present in 57% and of those, was not controlled in 73%. Forty-four percent were cigarette smokers at the time of death. Agreement between physicians and families was generally higher for clinical conditions than for care practices. This surveillance system appears to yield information about the health care of persons with diabetes not readily available from other sources, although modifications may be necessary before implementation.     

Changing attentional demands in left hemispatial neglect.

Seven variations of a letter cancellation test were used to examine how varying attentional demands affect hemispatial neglect in patients with right hemisphere lesions. While the 14 targets always remained in the same location, the number of distractors (zero, nine, 28, or 82) as well as their complexity (one letter or nine different letters) were varied. The percentage of targets canceled in the left hemispace was linearly related to the number of distractors. There were no differences between the complexity conditions. In a second study, the same 14 targets were presented but the distractors (zero, 14, or 41) were all placed on the right. Increasing the number of distractors on the right increased neglect on both sides of the space. Taken together, these results suggest that, while the limited attentional resources of the left hemisphere are biased toward the right hemispace, the absence of contralateral attentional demands allows these resources to be directed ipsilaterally.     

Recommendations for the evaluation and treatment of neonatal autoimmune and alloimmune thrombocytopenia. The Working Party on Neonatal Immune Thrombocytopenia of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH

The following recommendations of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH for the management of neonatal immune thrombocytopenia were prepared by the working party on neonatal immune thrombocytopenia. Evaluation, diagnosis, and treatment of the mother and neonate with alloimmune and autoimmune thrombocytopenia are discussed and current recommendations provided. This document is likely to require frequent future revision(s).