Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic responses of micro- and nano-particles of dolomite on human lung epithelial cells A(549)

Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A(549). The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-α, IL-1β and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite.     

Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture.

Alpha tocopheryl succinate treatment (6-8 micrograms/ml), which inhibited the growth of murine neuroblastoma (NBP2) cells (46 +/? 3%), reduced basal and prostaglandin (PG)E1- and PGA2-stimulated adenylate cyclase (AC) activity in vitro. It also inhibited sodium fluoride (NaF)- and forskolin-stimulated AC activity, suggesting that the effect of vitamin E succinate on AC activity is mediated via stimulatory GTP-binding protein (Gs) and catalytic subunit. Vitamin E succinate-induced reduction of AC activity is not strictly related to inhibition of cell growth. This is substantiated by the finding that, although retinoic acid and butylated hydroxyanisole reduced the growth by over 50%, they did not inhibit AC activity. On the other hand, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724, 200 micrograms/ml), which inhibited growth (73 +/? 3%) and induced differentiation in NB cells, increased basal and PGE1-stimulated AC activity. Vitamin E succinate treatment also reduced PGE1- and PGA2-AC activity in murine fibroblasts (L-cells) without inhibiting growth.     

Zinc deficiency in head and neck cancer patients.

Although a great deal of attention has been given to protein and calorie malnutrition in patients with head and neck cancer, zinc status has not been assessed properly in such patients in the past.

In this study we characterized zinc status by cellular zinc criteria and assessed several measures of protein and calorie malnutrition in patients with head and neck cancer. We determined prognostic nutritional index (PNI) based on serum albumin, serum transferrin, triceps skin fold measures, and delayed hypersensitivity, as proposed by Buzby et al. In this study, the baseline zinc status and PNI of 60 head and neck cancer patients were correlated with the tumor size and overall stage of the disease.

Our results showed that the tumor size and overall stage correlated significantly to zinc status whereas no correlation was seen with PNI, alcohol intake, or smoking in our study subjects.

We conclude that zinc status is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than the patients' overall nutritional status.     

Prolonged Stimulation of Corticosterone Secretion by Corticotropin-Releasing Hormone in Rats Exhibiting High Preference for Dietary Fat

Through the secretion of corticosterone, the hypothalamo-pituitary-adrenal (HPA) axis is thought to play an important role in the regulation of caloric intake and dietary fat preference. In an earlier study, we demonstrated a positive correlation between urinary corticosterone output and dietary fat preference. Furthermore, dietary fat preference was augmented following chronic but not acute hypercorticosteronemia produced by exogenous corticosterone administration. These observations led us to explore whether the HPA axis of rats exhibiting high preference for fat may have exaggerated sensitivity to corticotropinreleasing hormone (CRH). The results of these studies show a delayed and blunted but more prolonged corticosterone response to CRH in the fat-preferring rats compared with that of the carbohydrate-preferring rats.     

Ameliorative Effects of a Polyphenolic Fraction of Cinnamomum zeylanicum L. Bark in Animal Models of Inflammation and Arthritis

Cinnamon bark (Cinnamomum zeylanicum Syn C. verum, family: Lauraceae) is one of the oldest traditional medicines for inflammatory- and pain-related disorders. The objective of the present study was to evaluate the efficacy of the polyphenol fraction from Cinnamomum zeylanicum bark (CPP) in animal models of inflammation and rheumatoid arthritis. Dose-response studies of CPP (50, 100, and 200 mg/kg) used in a separate set of in vivo experiments were conducted in acute (carrageenan-induced rat paw edema), subacute (cotton pellet-induced granuloma), and sub-chronic (AIA, adjuvant-induced established polyarthrtis) models of inflammation in rats and the acetic acid-induced writhing model of pain in mice. Effects of CPP on cytokine (IL-2, IL-4, and IFNγ) release from Concanavalin (ConA)-stimulated lymphocytes were also evaluated in vitro. CPP showed a strong and dose-dependent reduction in paw volume, weight loss reversal effects against carrageenan-induced paw edema, and cotton pellet-induced granuloma models in rats. CPP (200 mg/kg p.o. for 10 days) showed a significant reduction in elevated serum TNF-α concentration without causing gastric ulcerogenicity in the AIA model in rats. CPP also demonstrated mild analgesic effects during acute treatment as evidenced by the reduction in the writhing and paw withdrawal threshold of the inflamed rat paw during the acetic acid-induced writhing model and Randall-Selitto test. CPP was found to inhibit cytokine (IL-2, IL-4, and IFNγ) release from ConA-stimulated lymphocytes in vitro. In conclusion, CPP demonstrated prominent action in animal models of inflammation and arthritis and therefore can be considered as a potential anti-rheumatic agent with disease-modifying action.     

Benign cervical thymoma masquerading as a malignant thyroid nodule

A thymoma in the neck region is a rare diagnosis involving a solitary neck nodule that moves with deglutition and is contiguous with the thyroid gland. The authors report an unusual case of a thymoma that accumulated both Tc-99m pertechnetate and Tc-99m MIBI. This is probably the first reported case of a benign neck thymoma concentrating these two radiopharmaceuticals. Thymoma should be added to the gamut of false-positive findings in the neck for thyroidal (with Tc-99m pertechnetate) and malignant (with Tc-99m MIBI) tissue.     

Differential expression of hZnT-4 in human prostate tissues

BACKGROUND: Altered zinc levels in prostate benign prostatic hyperplasia (BPH) and carcinoma is well documented. It is not known whether loss of zinc, necessary to restrain aggressive growth, results from loss of a single specific or multiple zinc transporters. METHODS: Human prostate tissues from patients who underwent radical prostatectomy were screened by RT-PCR analysis for five zinc transporters. Relative cDNA expression was determined in normal, BPH, and tumor specimens and four prostate epithelial cell lines. RESULTS: Surgical specimens were obtained from patients with assigned Gleason scores ranging from 5 to 9. Relative expression of hZIP-1 and hZnT-1 were prominent in most samples with relatively lesser degree of expression of hZIP-2 and no detectable expression of hZnT-3. Expression of hZnT-4 was decreased in BPH and tumor samples compared to normal tissue. CONCLUSIONS: These data suggest that zinc homeostasis in normal prostate tissues results from an interplay of multiple transporters and decreased hZnT-4 expression is associated with prostate tissue abnormalities independent of total cellular zinc content.