Biochemical Changes and Pulmonary Response of Guinea Pigs to Asbestos Dust

Abstract The biochemical and histopathological changes in lungs of guinea pigs were studied 120 days after intratracheal injection of three varieties of asbestos dusts, viz. chrysotile, amosite and anthophyllite. The salient histopathological features observed were the development of dust cell lesions in the lungs of animals exposed to the different varieties of asbestos. Maximum fibrosis and minimal asbestos body formation was observed in animals exposed to chrysotile and anthophyllite, respectively. With amosite and anthophyllite the development of diffuse interstitial fibrosis ensued, accompanied by well developed asbestos body formation in the amosite exposed animals. Biochemical studies revealed significant alterations in various phosphorylated compounds, an accumulation of orthophosphate and depletion of esters and nucleotides being very marked. RNA content increased significantly in the amosite treated group while the nucleic acid content remained unaltered in the chrysotile group.     

Comparison of molecular abnormalities in bronchial brushings and tumor touch preparations

BACKGROUND: Preneoplastic lung lesions and early-stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC). METHODS: Fourteen bronchial brushings ipsilateral to the tumor (BB/Ts), tumor touch imprints, and touch imprints of the bronchus adjacent to the tumor obtained from 15 patients with early-stage NSCLC were analyzed. The LAVysion multicolor probe set consisting of probes to 5p15, 6, 7p12, and 8q2 and the in-house probes 3p22.1 and 10q22 was used. Using the LAVysion multicolor probe set, 25 epithelial cells were counted and considered positive if > 5 cells were abnormal. Using 3p22.1 and 10q22, > or = 100 nuclei per slide were scored. The results were tabulated as the percentage of cells with deletions compared with the centromeric probes 3 and 10. Greater than 2% of the deletions were positive for 3p22.1 and 10q22. Bronchial washings from patients without lung tumors were used as controls. RESULTS: The BB/Ts were negative for malignant cells by cytologic evaluation and the LAVysion probe set; however, the combined in-house probes for 3p22.1 and 10q22 tested on BB/Ts predicted cancer in 100% of cancer patients. FISH positivity in the lung cancers was 100% for 3p22.1 deletions, 79% for 10q22 deletions, and 57% for LAVysion probes. When compared with the bronchial epithelium, tumor cells showed a 3.7-fold excess of 3p22.1 deletions, a 2-fold excess of 10q22 deletions, and a 12.6-fold excess of abnormal cells. CONCLUSIONS: The current study indicated that detection of molecular abnormalities in bronchial epithelial cells via FISH was very useful in identifying patients at high risk for developing lung carcinoma. The molecular abnormalities identified in the BB/Ts were detected at elevated levels in the tumor specimens.     

Positron-emission tomography imaging of early events after transplantation of islets of Langerhans

The aim of our study was to assess cell trafficking and early events after intraportal islet transplantation. Sprague-Dawley rat islets were incubated for various times, with various concentrations of 2-[F]fluoro-2deoxy-D-glucose (FDG), and in presence of various glucose concentrations. FDG-labeled syngeneic islets or FDG alone were injected in rats. Radioactivity was measured in the liver and in various organs by positron-emission tomography for 6 hours. FDG uptake increased with incubation time or FDG concentration and decreased in presence of glucose. In vivo, all islets implanted in the liver, with an uptake 4.4 times higher than controls (44.2% vs. 10.1%, P=0.02). Radioactivity in the liver decreased at the same rate after injection of labeled-islets and FDG alone. Ex vivo labeling of islets and imaging of posttransplant early events were feasible. Islets engrafted exclusively in the liver. No islet loss could be demonstrated 6 hours after transplantation.     

Early biochemical alterations in manganese toxicity: ameliorating effects of magnesium nitrate and vitamins

Manganese-induced early biochemical changes and effects of supplementation of magnesium nitrate (Mg(NO3)2) and antioxidant vitamins (A, C, D and E) were studied in rats intoxicated with manganese. Significant elevation in the level of chlorides in plasma, erythrocytes, liver and cerebellum, and a decrease in plasma inorganic phosphate (pi) with an increase in liver pi were observed in animals exposed to manganese as compared to controls. The level of erythrocyte-acid labile phosphate (ALP), nicotinamide adeninedinucleotide (NAD+) and plasma sialic acid (N-acetylneuraminic acid, NANA) also increased significantly. Elevated levels of chlorides in plasma, erythrocytes and cerebellum reversed to normal control values whereas liver chlorides restored partially by the supplementation of Mg(NO3)2. Vitamins supplementation was effective to reverse chlorides level in erythrocytes, liver and cerebellum. Decreased level of pi in plasma and the highly elevated level of erythrocyte ALP were also recovered in animals received Mg(NO3)2 in addition to MnSO4. However, such effect of Mg(NO3)2 was not seen in lowering the elevated level of NANA that restored by the administration of vitamins. Thus, the early alterations in plasma levels of chlorides, pi, and NANA and erythrocyte-ALP seem to be an indicative of early manganese toxicity while Mg(NO3)2 and vitamins supplementation appear to provide, at least in part, protection against manganese toxicity.     

Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake

Calcium malabsorption, hypocalcemia and skeletal demineralization are well-recognized features of untreated celiac disease. This study investigates calcium absorption and bone mineral density (BMD) after a prolonged, over 4 years, treatment with a gluten-free diet. Twenty-four adult females with treated celiac disease and twenty age- and sex-matched control subjects were studied. Mean body mass index (MBI), energy intake, serum calcium, and serum 25(OH)D concentrations in treated celiacs did not differ from controls. However, while both dietary calcium and protein intake were significantly higher in celiacs (P<0.012), fractional calcium absorption was lower (mean percentage±SD; treated 39.8±12 versus controls 52.3±10, P<0.001). Thus, after adjusting for calcium intake, the estimated amount of calcium absorbed daily was similar in both groups. Whole body, spine and trochanter BMD were significantly lower in treated celiac patients compared with controls (P<0.05). There were significant inverse correlations between: serum parathyroid hormone (PTH) and femoral neck or total body BMD (P<0.01), PTH and duration of gluten-free diet (P=0.05), and fractional calcium absorption and alkaline phosphatase (P=0.022). Increased calcium intake could potentially compensate for the reduced fractional calcium absorption in treated adult celiac patients, but may not normalize the BMD. In addition, the inverse correlation between PTH and time following treatment is suggestive of a continuing long-term benefit of gluten withdrawal on bone metabolism in celiac patients.