Sublingual gland neoplasms: clinicopathological study of 8 cases.

BACKGROUND: Sublingual gland neoplasms are very rare and the majority of them are malignant. The aim of this study was to evaluate the clinical course, treatment, and outcomes of these uncommon neoplasms based on the authors' experience and the recent literature. MATERIAL AND METHODS: The medical charts of 8 patients with primary epithelial sublingual gland tumors treated between 1994 and 2020 were reviewed. RESULTS: Malignant tumors comprised 75% (6/8) of cases. Adenoid cystic carcinoma was the most common (50%, 3/6) and characterized by high risk of local recurrence and lung metastasis. Pleomorphic adenoma was the only representative of benign tumors with no evidence of local recurrence in follow up. CONCLUSIONS: Treatment of choice of sublingual gland tumors is surgery. However, due to the fact that adenoid cystic carcinoma is the most common malignancy with poor prognosis, surgical treatment should be combined with postoperative radiotherapy. Benign sublingual tumors are less common and treatment of choice in these cases is tumor resection together with sublingual gland.

Effects of neuraminidase on apoptosis of blood lymphocytes in rats with implanted Morris tumor.

In this study we examined the influence of neuraminidase on apoptosis of peripheral blood lymphocytes in rats with an implanted Morris tumor. The main objectives of the study were to determine whether the percentage of apoptotic blood lymphocytes would depend on the dosing regimen of neuraminidase and whether neuraminidase would affect caspase-3 activity, a marker of the apoptosis, in blood lymphocytes. A total of 51 rats were used for the study. In three groups, totalling 39 animals, Morris tumor was implanted and neuraminidase was injected intravenously using two dosing regimens: 10 units three times on Day 4, Day 7, and Day 14 and 5 units as a single dose on Day 4 of the experiment or was skipped (control). The remaining 12 rats constituted a reference group of healthy animals. At the end of the experimental period on Day 21, blood was drawn from the heart, and mononuclear cells were separated and cultured. Apoptosis of blood lymphocytes was assessed in cell cultures from fluorescence spectra generated by a Sybr Green I dye forming bonds with nuclear DNA. Caspase-3 activity was measured colorimetrically in homogenates of lymphocyte cultures using a CASP-3-C kit (Sigma, St. Louis, MO). On the whole, the results demonstrate that the bigger, but not the smaller, dose of neuraminidase was markedly effective in preserving the vitality of blood lymphocytes and in decreasing both the number of apoptotic lymphocytes and capsase-3 activity in the rats with Morris tumor. Neuraminidase treatment failed, however, to lessen the tumor size. In conclusion, the study demonstrates that neuraminidase caused an appreciable decline in apoptosis of blood lymphocytes in rats with the Morris tumor; the effect was dose-dependent. Although neuraminidase failed to influence the local cancer development in terms of tumor size, its anti-apoptotic effect toward the cells of the immune system of a cancer host is of research interest as it may potentially offer a way to strengthen the host's immune response.

DNA repair of hydrogen peroxide-induced damage in human lymphocytes in the presence of four antimutagens. A study with alkaline single cell gel electrophoresis (comet assay).

We assessed four antimutagenic compounds' influences on DNA repair in human lymphocytes exposed in vitro to hydrogen peroxide (20 microM, 5 min, at 4 degrees C). DNA damage and repair were estimated by means of alkaline single cell gel electrophoresis (comet assay). It was noticed that the enhancement of DNA repair was relatively strongest when fluphenazine was present in the cell culture medium. In the cases of anthocyanins and alkylresorcinols, the effects were almost 6-9 times weaker than that of FPh. The effect of todralazine on DNA repair was relatively weakest. Further study should be done on fluphenazine as a potential DNA repair-enhancing compound.

Impact of four antimutagens on apoptosis in genotoxically damaged lymphocytes in vitro.

An antimutagenic activity of fluphenazine, todralazine, anthocyanins and alkylresorcinols was established in a battery of short-term cytogenetic tests. One of the possible mechanisms of their antimutagenic action could be an increase in apoptotic elimination of heavily-damaged cells from a culture. In this paper we provide data on quantitative estimation of the antimutagens' impact on apoptosis in lymphocyte cultures exposed in the G(0)-phase to genotoxic agents: hydrogen peroxide (0.2mM, 20 min.) or benzo[a]pyrene (40 microM, 90 min.), and then cultured for 36 hrs in the presence of a lectin (PHA-M, 1% v/v) and each of the tested antimutagens. Apoptosis was estimated by means of microscopic examination of cell smears stained with a mixture of fluorochromes (ethidium bromide/acridine orange) as well as of the results of DNA separation with the field inversion gel electrophoresis. By microscopic examination we assessed that the frequencies of cells exhibiting morphological features of apoptosis considerably increased in the cultures containing the antimutagens. The FIGE separation of DNA from those cultures proved that the DNA content in the 30-50 kb domain was markedly elevated, as compared with the control cultures that did not contain antimutagens. It was established in the regression analysis that the apoptosis-enhancing effect significantly depended on the concentration of each tested antimutagen in a culture medium. However, marked differences of apoptosis-enhancing potency were noticed among the four antimutagens. The multicriterial analysis proved that the apoptosis-enhancing effects of fluphenazine and also, to a smaller extent, by alkylresorcinols, were many times stronger than those of anthocyanins and of todralazine. The results suggest that the enhancement of apoptosis by fluphenazine and by alkylresorcinols can explain a major part of their antimutagenic activity, whereas in the case of anthocyanins and of todralazine other mechanisms of antimutagenic action should be sought for.

A comparison of the methods applied to detect apoptosis in genotoxically-damaged lymphocytes cultured in the presence of four antimutagens.

The sensitivity of the available methods of apoptosis detection in lymphocyte cultures was tested. Cells were preincubated with genotoxic agents: hydrogen peroxide (0.2 mM; 20 min.) and benzo[a]pyrene (40 microM; 90min.), and then cultured for 36h in the presence of a lectin (PHA-M; 1% v/v) and one of the following potentially antimutagenic agents: alkylresorcinols, anthocyanins, todralazine and fluphenazine. It was established that staining with a mixture of fluorochromes (ethidium bromide and acridine orange) provided the highest amount of detected apoptotic cells, and the best repeatability of the results in subsequent experiments. Calculation of the Spearman's rank correlation coefficients proved that there was a high correlation between the results obtained by the ethidium bromide/acridine orange method and those obtained by identifying genomic DNA fragmentation by means of FIGE-electrophoresis. Therefore, these two methods were chosen for further studies of the tested antimutagens' impact on apoptosis in genotoxically-damaged lymphocytes.

Antimutagenic activity of fluphenazine in short-term tests.

Fluphenazine, an antipsychotic drug that belongs to the phenothiazine family, reduced the genotoxicity of direct- and indirect-acting mutagens in the Ames test, both in the presence and in the absence of promutagen-activating S9 fraction. In short-term tests on human lymphocytes, the inhibitory effect of fluphenazine on the genotoxicity of standard mutagens was strongest in the cytokinesis-blocked micronucleus assay and in the thioguanine resistance test, and weakest in the sister chromatid exchange test. Fluphenazine also considerably reduced the level of free radicals estimated in in vitro samples of human granulocytes. The results suggest that, in the range of the tested concentrations, fluphenazine could be considered for use to prevent the genotoxicity of daunorubicin, methyl methanesulfonate, benzo[a]pyrene, and mitomycin C. Reduction in the level of free radicals appears to be an important mechanism of the antimutagenic action of fluphenazine.

Evaluation of antimutagenic effect of todralazine in cultured lymphocytes.

Todralazine, an antihypertensive drug from the hydrazinophthalazine group, significantly decreased the activities of benzo[a]pyrene and mitomycin C in three short-term genotoxicity tests in human lymphocyte cultures. The thioguanine resistance test, the cytokinesis-blocked micronucleus assay and the sister chromatid exchange test were used to demonstrate the antimutagenicity of todralazine. Todralazine lowered the level of free radicals generated by human granulocytes in vitro in the presence of benzo[a] pyrene and also in the presence of the granulocyte activator and tumor promoter phorbol myristate acetate. These results, together with our previous data obtained in the standard bacterial Ames test, strongly suggest that todralazine is a good antimutagen in vitro and deserves further research on its inhibitory action on mutagenesis and carcinogenesis.

Evaluation of genotoxic and immunotoxic activities of potential glucose biosensor components: ferrocenes.

Three ferrocenes used in glucose biosensor construction were tested in the aspect of genotoxic and immunotoxic activities. All three ferrocenes were not mutagenic in the standard bacterial Ames test. Equally in the Sister Chromatid Exchanges test in human lymphocyte cultures, the genotoxic action of tested ferrocenes could be excluded. However, all three significantly decreased the rate of lymphocyte proliferation and especially diminished the numbers of B-lymphocytes and NK-cells after 72 hours of in vitro culture. Marked differences between the ferrocenes in their immunotoxic activities were noticed, and we were able to select those which would be relatively safe and those which should be avoided in further investigation of the glucose biosensor construction. Our results indicate the necessity to estimate immunotoxic effects as well as genotoxic effects, especially in biosensor components potentially used in vivo.

Inhibition of potassium dichromate mutagenicity by todralazine.

Todralazine, an antihypertensive drug of the hydrazinoph-thalazine group, markedly decreased the mutagenic activity of potassium dichromate in standard bacterial tests. At the highest todralazine dose tested inhibition of potassium dichromate mutagenic activity by approximately 90% in the Ames test and up to 100% (complete) inhibition in the Bacillus subtilis rec- assay was observed. Spectrophotometric analyses proved that todralazine induced reduction of Cr(VI) to Cr(III) and complexation of Cr(III) ions. These spectro-photometric results may be a presumptive explanation of the observed mutagenic activity decrease, as it is known that Cr(III) is poorly transported across cell membranes and therefore is not mutagenic to bacterial cells. We perceive our experiments as an example of attempts which should lead to an effective reduction in chromium genotoxic and carcinogenic activity in exposed individuals.

A proposed new strategy of immunotherapy for Alzheimer's disease.

Current data on the involvement of the immunological system in the pathogenesis of Alzheimer's disease (AD) are discussed, and results of immunotherapy for the disease are provided. Hypotheses on immune aging as a risk factor for AD, and a suggested new treatment strategy, are presented and discussed.

Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits.

Anthocyanins belong to the flavonoid family and are ubiquitous in plants, especially in flower petals and fruit peels. We established that anthocyanins isolated from fruits of Aronia melanocarpa markedly inhibited the mutagenic activity of benzo(a)pyrene and 2-amino fluorene in the Ames test. In the Sister Chromatid Exchanges (SCEs) test with human blood-derived lymphocytes cultured in vitro, a significant decrease of SCEs frequency induced by benzo(a)pyrene was observed in the presence of anthocyanins. In the case of mitomycin C the effect of anthocyanins on SCEs frequency was smaller but still noticeable. Anthocyanins markedly inhibited the generation and release of superoxide radicals by human granulocytes. The results suggest that the antimutagenic influence of anthocyanins is exerted mainly by their free-radicals scavenging action as well as by the inhibition of enzymes activating promutagens and converting mutagens to the DNA-reacting derivatives. These preliminary data seem to be important in the aspect of a possible antimutagenic and anticarcinogenic potency of anthocyanins commonly present in fruits and vegetables.

Antimutagenic activity of alkylresorcinols from cereal grains.

Alkylresorcinols, natural amphiphilic compounds commonly found in cereal grains, markedly decreased mutagenic activity of four standard mutagens examined in the Ames test. The effect was the strongest in the case of indirect-acting mutagens, benzo[a]pyrene and 2-aminofluorene. In the case of direct-acting mutagens, daunorubicin and methyl methanesulfonate, the diminution of the mutagenic activity by the alkylresorcinols was smaller but still noticeable. In the Sister Chromatid Exchanges test (SCEs) with cultured in vitro human blood-derived lymphocytes, a significant decrease of SCEs frequency induced by benzo[a]pyrene was observed in the presence of alkylresorcinols. These preliminary results seem to be important in the aspect of possible antimutagenic and anticarcinogenic potency of alkylresorcinols found in cereal grains.

Evaluation of the mechanisms of todralazine effect on mutagenicity of benzo(a)pyrene.

We have previously described that todralazine markedly decreased mutagenicity of several indirect- and direct-acting mutagens. In this paper we report the results of experiments conducted in order to evaluate the involvement of desmutagenic and bio-antimutagenic activities in the observed antimutagenic effect of todralazine. The results of the Ames test suggest a bio-antimutagenic, and not desmutagenic effect of todralazine. The separation of B(a)P and their derivatives by thin layer chromatography, performed after in vitro incubation of this promutagen with S9 fraction and todralazine revealed almost complete decline of B(a)P derived products in the presence of todralazine. The results indicate that the observed antimutagenic effect of todralazine on B(a)P mutagenicity is bio-antimutagenic rather than desmutagenic in their nature.

[Neurotrophic growth factors in Alzheimer's disease]. / Neurotroficzne czynniki wzrostowe w chorobie Alzheimera.

In recent years disturbances in releasing neurotrophic growth factors have been viewed as one of the causes of the development of Alzheimer's disease. It is assumed that abnormalities concerning neurotrophic growth factors (e.g. disturbances in releasing them and (or a wrong response of nerve cells to released growth factors) may be co-responsible for the development of abnormal functions of recent memory or concentration. It is assumed that their role in neurodegenerative processes consists primarily of increasing the survival rate of nerve cells and exerting an effect on the transmitting functions of CNS neurons. Attempts made at present to use growth factors in A.D. with a view to increasing the survival rate of degenerating nerve cells and improving the transmitting functions of neurons will be continued in future in pace with the advancement of our knowledge of their mechanisms.

Todralazine influence upon the mutagenicity of some direct- and indirect-acting mutagens.

Todralazine decreased the mutagenic activity of tested direct- and indirect-acting mutagens. Despite the marked differences between efficient todralazine doses (ED50) it was observed that, in the case of tested indirect mutagens as well as in some of the direct mutagens, the decrease of mutagenicity by todralazine was very strong, exceeding 80% in some cases.

Study of the mechanism of todralazine antimutagenic activity: the effect upon mutagenicity of daunorubicine.

Todralazine markedly reduced the mutagenic activity of the standard direct-acting mutagen--daunorobicine (DRC)--in the Ames test. Spectrophotometric measurements proved that todralazine did not interact with DRC in water solution. Todralazine neither interacted with calf thymus DNS in vitro, nor changed the interaction of DRC with DNA. Therefore we concluded that the decrease of DRC mutagenicity observed in the Ames test should be explained rather in terms of a bioantimutagenic than a desmutagenic activity of todralazine.

Mutagenic activity of drinking water in Wroclaw, Poland.

The Salmonella mutagenicity test was applied to the evaluation of mutagenic activity of Wroclaw drinking water. Contaminants of water samples were concentrated by adsorption on XAD-2 resin. After while they were eluted sequentially with acetone, dichloromethane/methanol (1:1, v/v) and methanol, and then obtained organic extracts were evaporated to dryness. The extracts were then dissolved in DMSO and examined by using the Ames test. The results proved significant contamination of drinking water with mutagenic substances. Hydroxyapatite column chromatography performed after direct incubation of standard DNA probes with tested water extracts showed that drinking water was contaminated with DNA interstrand cross-linking substances. Filtration of tap water through carbon filters markedly reduced mutagenic activity of tested water extracts, whereas ceramic filters were more efficient in depleting of DNA interstrand cross-linking contaminants.

Alzheimer's disease--immunological aspects.

Alzheimer's Disease (A.D.) is a multifarious, complex syndrome, which probably comprises different etiopathogenic subunits. Work by several authors has shown immunological disturbances in A.D. underlining the importance of immunological imbalance in the explanation of the etiopathogenesis and progress of some forms of A.D. An early diagnosis of A.D. is important because changes in central nervous system respond well to immunomodulatory treatment in the early course of disease. This justifies a search for diagnostic methods permitting an early diagnosis of the disease and establishment of immunological disturbances and consequently an early start of treatment. In the present paper, the literature regarding immunological disturbances observed in A.D. patients is reviewed.

Mutagenicity of B(a)P in the presence of some hydralazine derivatives.

Hydralazine, dihydralazine and todralazine were tested in the aspect of their mutagenic potency, and the influence upon the mutagenicity of standard promutagen--B(a)P. Hydralazine exhibited strong mutagenic activity in the Ames test while mutagenic activity of dihydralazine was relatively weak. Todralazine had no mutagenic activity, and significantly decreased mutagenicity of B(a)P. It was concluded that todralazine could be a good antimutagenic substance.