G cells and gastrin in chronic alcohol-treated rats.

Numerous reports have described gastric mucosal injury in rats treated with high ethanol concentrations. However, to the best of our knowledge, ultrastructural characteristics of G cells and antral gastrin levels have not been previously reported, either in rats that chronically consumed alcohol or in human alcoholics. The goal of this study was to examine the effect of ethanol consumption (8.5 g/kg) over a 4-month period, under controlled nutritional conditions, on antral and plasma levels of gastrin, ultrastructure of G cells, morphometric characteristics of G cells by stereological methods, and analysis of endocrine cells in the gastric mucosa by immunohistochemistry. The chronic alcohol consumption resulted in a nonsignificant decrease in gastrin plasma levels and unchanged antral gastrin concentrations. A slightly damaged glandular portion of the gastric mucosa and dilatation of small blood vessels detected by histological analysis, suggests that ethanol has a toxic effect on the mucosal surface. Chronic alcohol treatment significantly decreased the number of antral G cells per unit area, and increased their cellular, nuclear, and cytoplasmatic profile areas. In addition, the volume density and diameter of G-cell granules, predominantly the pale and lucent types, were increased, indicating inhibition of gastrin release. Ethanol treatment also decreased the number of gastric somatostatin-, serotonin-, and histamine-immunoreactive cells, except the somatostatin cells in the pyloric mucosa, as well as both G: D: enterochromaffin cells (EC) cell ratios in the antrum and D: ECL cell ratios in the fundus. These results indicate that the change of morphometric parameters in G cells may be related to cellular dysfunction. Our findings also suggest that regulation of G-cell secretion was not mediated by locally produced somatostatin in ethanol-consuming rats, but may involve gastric luminal content and/or neurotransmitters of gastric nerve fibers.     

Synergistic effects of recombinant human tumor necrosis factor and hyperthermia on in vitro cytotoxicity and artificial metastasis

Synergy in cytotoxic effect between recombinant human tumor necrosis factor and hyperthermia (incubation at 38.5 degrees C or 40 degrees C) was observed to occur against L-M (mouse tumorigenic fibroblast) cells and shown to be related to an accelerated turnover rate of recombinant human tumor necrosis factor-receptor complex under elevated temperatures rather than to changes in number of cell receptors or binding strength. However, no synergy in cytotoxic effect was observed to occur against human embryonic lung (HEL) cells. A clearly synergistic inhibition of metastatic tumor growth by combined administration of recombinant human tumor necrosis factor (300 units) and whole-body hyperthermia (40 degrees C, 30 min) was also observed in BALB/c mice previously given injections of 1 x 10(6) Meth-A (MH) cells/mouse via tail vein, neither of which alone resulted in significant inhibition.     

Mechanism of the cytotoxic effect of tumor necrosis factor

The mechanism of murine tumor necrosis factor (TNF) cytotoxicity against tumor cell lines (L929, HeLa, K562) was investigated. Electron microscopic observation revealed that most of the organellas of L929 cells incubated with partially purified murine TNF underwent almost complete lysis with no drastic disruption of the cytoplasmic membrane, while injection of the TNF into the cytoplasm or nuclei of L929 cells caused no apparent morphological change or growth inhibition. Preincubation of the TNF with tumor cells (L929, HeLa, K562) resulted in a decrease in cytotoxic activity which was proportional to their susceptibility to TNF, thus indicating their absorption of TNF. The susceptibility of L929 tumor cells to TNF was apparently suppressed by treatment with proteases, suggesting the existence of protease-sensitive recognition sites for TNF on the tumor cell.     

Synergistic Cytotoxicity of Recombinant Human TNF and Various Anti-Cancer Drugs

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and anti-cancer drugs was demonstrated in vitro. The cytotoxicity of rH-TNF against L-M cells in combination with Mitomycin C (MMC), Adriamycin (ADM), Cytosine arabinoside (Ara-C), Actinomycin D (ACD), Daunomycin (DM), Cisplatin (CDDP), Vincristin (VCR), and 5-Fluorouracil (5FU), based on the concentration necessary for 50% inhibition of cell growth (IC50), was 4 to 347 times as high as that of rH-TNF alone. The results suggest that combination therapy including rH-TNF and anti-cancer drugs may be of value in the treatment of malignancy in human patients.     

Mediastinal neuroendocrine tumours

The spectrum of neuroendocrine tumours that may arise in the mediastinal compartment is as varied as their clinical behaviour. Because these tumours may share similar histological features and immunohistochemical profile, it is essential to properly establish a good clinical–radiological and pathological correlation. Some of these tumours by virtue of sharing similar histological features and immunoprofile may be classified into tumours that require more aggressive treatment while in fact they may represent tumours of indolent behaviour in which surgical resection is the treatment of choice. Herein we will review the most salient features of this group of tumours and highlight the important pitfalls in their interpretation, and more importantly their separation into specific entities. In addition, in some of the more aggressive neoplasms, the importance of proper classification is emphasized to provide more meaningful information regarding prognosis and behaviour of the tumour.     

Augmented Systemic Immunity in Mice Implanted with Tumor Necrosis Factor-α Gene-transduced Meth-A Cells

Syngeneic BALB/c mice bearing methylcholanthrene-induced fibrosarcoma (Meth-A) cells transduced with a tumor necrosis factor (TNF) gene showed a longer life span and tumor regression as compared with mice carrying TNF-non-producing Meth-A cells. To elucidate the mechanism of the reduced tumorigenicity of TNF-producing Meth-A, we compared systemic immune responses between mice bearing high TNF producer (C5) and unmodified Meth-A cells (M0). The results indicated that the cytotoxic activity of lymphokine-activated killer cells (LAK) induced from spleen cells of mice bearing C5 was higher against both M0 and C5 than that of LAK from mice bearing M0. Also, C5 was more sensitive to LAK induced from spleen cells of C5- and M0- bearing mice than M0. We also found that cytotoxic T lymphocyte from spleen cells of mice transplanted with C5 was more cytotoxic to M0 than that from mice with M0. In addition, the population of Lyt2 (CD8)-positive T cells was higher in freshly isolated spleen cells of mice transplanted with C5 than from mice with M0. Finally, we observed a higher expression of MHC class 1 antigen on C5 than on M0. These observations suggest that the augmented host systemic immunity in mice carrying TNF gene-modified Meth-A cells is one of the mechanisms of the reduced tumorigenicity of C5 and that the increased systemic immunity can be ascribed to the increased immunogenicity of the tumor cells. Thus, the use of TNF gene-modified tumor cells as vaccines appears to be promising for therapeutic and/or prophylactic application.     

Antibacterial effect and physicochemical properties of essential oil of Zataria multiflora Boiss

ObjectiveTo evaluate the antibacterial effect and physicochemical properties of essential oil of Zataria multiflora Boiss.MethodsAntibacterial activity of essential oil of Zataria multiflora Boiss was assessed by agar disc diffusion and minimal inhibitory concentration(MIC) was tested by E test.ResultsThe essential oil of Zataria multiflora Boiss was effective on pathogenic bacteria particularly Staphylococcus aureus (S. aureus). The MIC values of the target cultures ranged from 0.39 mg/mL to 1.56 mg/mL. The physicochemical properties like effects of pH, temperature, detergents, and enzymes on the activity of essential oil from Zataria multiflora Boiss were also determined. The essential oil was quite stable to temperature as tested against S. aureus and Escherichia coli (E. coli). The essential oil was very stable over a wide range of pH. The antibacterial activity of essential oil was insensitive to various protein-denaturing detergents (Such as Tween 80, Tween 20, Triton 100, etc.) and enzymes (namely proteinase K, trypsin, lipase, and lysosyme).ConclusionsA potential use of the essential oil from Zataria multiflora Boiss is suggested. More studies including further purification, mass spectra, nuclear magnetic resonance (NMR) and evaluation of toxicity are needed for confirmation of this suggestion.