Exposure to zinc oxide (ZnO) metal fumes is linked to adverse human health effects; however, the hazards of ZnO nanoparticles (ZnONPs) remain unclear. To determine pulmonary exposure to occupationally relevant ZnONPs cause cardiopulmonary injury, Sprague-Dawley rats were exposed to ZnONPs via intratracheal (IT) instillation and inhalation. The relationship between intrapulmonary zinc levels and pulmonary oxidative-inflammatory responses 72 h after ZnONP instillation was determined in bronchoalveolar lavage fluid (BALF). Instilled ZnONPs altered zinc balance and increased the levels of total cells, neutrophils, lactate dehydrogenase (LDH) and total protein in BALF and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in blood after 72 h. The ZnONPs accumulated predominantly in the lungs over 24 h, and trivial amounts of zinc were determined in the heart, liver, kidneys and blood. Furthermore, the inflammatory-oxidative responses induced by occupationally relevant levels of 1.1 and 4.9 mg/m(3) of ZnONP inhalation for 2 weeks were determined in BALF and blood at 1, 7 and 30 days post-exposure. Histopathological examinations of the rat lungs and hearts were performed. Inhalation of ZnONP caused an inflammatory cytological profile. The total cell, neutrophil, LDH and total protein levels were acutely increased in the BALF, and there was an inflammatory pathology in the lungs. There were subchronic levels of white blood cells, granulocytes and 8-OHdG in the blood. Cardiac inflammation and the development of fibrosis were detected 7 days after exposure. Degeneration and necrosis of the myocardium were detected 30 days after exposure. The results demonstrate that ZnONPs cause cardiopulmonary impairments. These findings highlight the occupational health effects for ZnONP-exposed workers.

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Silver nanoparticles (AgNP) have been associated with the exacerbation of airway hyperresponsiveness. However, the allergenicity and toxicology of AgNP in healthy and allergic individuals are unclear. We investigated the pathophysiological responses to AgNP inhalation in a murine model of asthma. Continuous and stable levels of 33 nm AgNP were maintained at 3.3 mg/m 3 during the experimental period. AgNP exposure concomitant with ovalbumin challenge increased the enhanced pause (Penh) in the control and allergic groups. AgNP evoked neutrophil, lymphocyte and eosinophil infiltration into the airways and elevated the levels of allergic markers (immunoglobulin E [IgE] and leukotriene E 4 [LTE 4 ]), the type 2 T helper (Th2) cytokine interleukin-13 (IL-13), and oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG]) in healthy and allergic mice. Bronchocentric interstitial inflammation was observed after AgNP inhalation. After inhalation, the AgNP accumulated predominantly in the lungs, and trivial amounts of AgNP were excreted in the urine and feces. Furthermore, the AgNP induced inflammatory responses in the peritoneum. The inhalation of AgNP may present safety concerns in healthy and susceptible individuals.

DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.

We describe here a patient with an unusual presentation--mesenteric calcifying fibrous pseudotumor in association with jejunojejunal intussusception. This 25-year-old woman came to our emergency department with severe abdominal distension and intermittent epigastric cramping pain. She was found to have rebound tenderness and an ill-defined mass palpable in her lower abdomen. Abdominal computed tomography revealed an inhomogeneous soft tissue mass with target sign and intussusception of small intestine was suspected. Emergency laparotomy showed jejunojejunal intussusception involving ~30cm of jejunum with multiple tumors on the mesentery surface extending over the whole bowel mesenteric and peritoneal surfaces. One of the mesenteric tumors formed the leading point of the intussusception. Segmental resection of jejunum with primary anastomosis was done. Some larger tumors were resected but most of the other tumors were left in place because they were small and numerous and total resection was impossible. Pathology confirmed that the lesions were benign mesenteric calcifying fibrous pseudotumors. In such patients, surgery might be curative. If a large segment of the bowel is affected by calcifying fibrous pseudotumor, smaller pseudotumors might be left in place because these tend to be asymptomatic. But they might become the leading points of recurrent intussusception.