Atypical blast morphology of primary plasma cell leukemia with renal involvement and plasmablasts in urine

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell (PC) myeloma characterized by high levels of circulating PCs. Clinical presentation is like other acute leukemia, with extramedullary infiltration of various tissues and organs being a frequent complication. The disease has a fulminant course and poor prognosis. Morphology of PCs in PCL includes a spectrum of maturity, with most cases having lymphoplasmacytoid or plasmablastic morphology. Presentation as more primitive cells that do not resemble PCs is even rarer and requires additional morphological and immunophenotypic studies. We present a case of 79‐year‐old woman who presented with severe pancytopenia and lobar pneumonia. Laboratory and clinical evaluation revealed primary, nonsecretory PCL with atypical, immature blast morphology, extramedullary renal involvement, and plasmablasts in urine. Despite therapeutic efforts the patient succumbed to the disease. Detection of PCs in the urine indicates extramedullary spread of disease, especially without accompanying hematuria, and may contribute to impairment of renal function, what is already a frequent complication in these patients. Diagn. Cytopathol. 2015;43:158–162. © 2014 Wiley Periodicals, Inc.     

Acute doxorubicin pulmotoxicity in rats with malignant neoplasm is effectively treated with fullerenol C60(OH)24 through inhibition of oxidative stress

The aim of this study was to investigate the possible protective role of fullerenol (FLR, C₆₀(OH)₂₄ on doxorubicin (DOX)-induced lung toxicity using biochemical and histopathological approaches. Rats (Sprague-Dawley outbred) were randomly divided into five groups. The healthy control group received no medication (saline only). The other four groups had chemically induced breast cancer (1-methyl-1-nitrosourea; 50 mg/kg, ip). The second group was the cancer control group (saline only). The other three groups were DOX (8 mg/kg, ip), FLR/DOX (100 mg/kg, ip, 30 min before DOX; 8 mg/kg, ip), and FLR (100 mg/kg, ip), respectively. The levels of malondialdehyde (MDA) and oxidized glutathione (GSSG) in the lung tissue were higher in the group treated with DOX alone than in the control groups. The activities of catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), and lactate dehydrogenase (LDH) were found to be increased in the lung tissue of the animals in the DOX group over all the other groups, while GSH-Px significantly decreased in activity compared with the control and FLR groups. There was no significant difference in MDA and GSSG levels and enzyme activities in either control (healthy; cancer) or FLR (FLR/DOX; FLR) groups. The acute change found in the DOX group was subpleural edema. In contrast, the groups treated with FLR appeared to be virtually histopathologically normal.In conclusion, this study clearly indicates that DOX treatment markedly impairs pulmonary function and that pre-treatment with FLR might prevent this toxicity in rats through inhibition of oxidative stress.     

Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin

Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or “scaffold” to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 μg/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25 mg/kg, 10 mg/kg i.v.), warfarin (1.5 mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1 g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10 mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (< 20% of initial values in heparin-rats) approaches substantial fall in platelets count known in type II HIT. Also, BPC 157 markedly prolongs the survival time (heparin-rats, 25 mg/kg, right foot amputation).     

NOD2/CARD15 mutations in Croatian patients with Crohn's disease: prevalence and genotype-phenotype relationship

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. AIMS AND METHODS: As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis. RESULTS: NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. CONCLUSIONS: This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.     

Cholinesterase‐Inhibiting and Genotoxic Effects of Acute Carbofuran Intoxication in Man: A Case Report

Abstract: Carbofuran belongs to the group of N‐methylcarbamate insecticides used for the control of soil‐dwelling and foliar‐feeding insects in various crops; its consumption totals approximately 20,000 tonnes per year. Although the neurological effects on human beings have been well documented, little is known on its impact on the genome. A 38‐year‐old, healthy male worker employed in a carbofuran production facility accidentally inhaled the dust of the active ingredient carbofuran. Thirty minutes later, he experienced weakness, fatigue, perspiration, breathing difficulties, cephalalgia, disorientation, abdominal pain and vomiting. Blood samples were taken to measure cholinesterase activity, and to perform the alkaline comet assay and micronucleus assay combined with pancentromeric probes. Analyses were repeated 72 hr after intoxication and compared with the results obtained from regular monitoring conducted 10 days prior to the accident. Cholinesterase activity showed the highest correlation with the number of apoptotic cells, comet assay tail length, and number of long‐tailed nuclei, suggesting that these are the genomic end‐points primarily affected by carbofuran intake. Only a weak correlation was detected for the total number of micronuclei, centromere‐containing micronuclei and nuclear buds. Since those end‐points increased significantly 72 hr after the accident, they could be considered as late biomarkers of the effects of carbofuran intoxication. The results of this report suggest that, in the interests of higher standards in risk assessment and health hazard protection, periodical medical examination of carbamate‐exposed populations should include genotoxicity testing in addition to the assessment of cholinesterase activity.