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Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to explosive performance in elite handball players
No full textTen handball players, members of the Italian National Team (aged 20–25 years), were studied in two sessions corresponding to different performance levels. The first session occurred one week after the end of the regular season of the Italian Handball ederation: it corresponded to the beginning of the training cycle for the European Handball Championship. The second session occurred ten weeks after the first session. During this period, training consisted of 3 weeks of active recovery and 7 weeks
of increasing workload. For each session, jumping performances (maximal height in a single jump, average mechanical power for a 15-s set of consecutive jumps) were evaluated. Venous blood samples were collected in resting conditions immediately before jumping performances to assess cortisol and testosterone plasma concentrations and glucocorticoid receptors (GcR) binding capacity and affinity in peripheral blood mononuclear cells (PBMCs). All the parameters, except GcR binding affinity, increased in the second session. The trends of variation in jumping performances, steroid hormone levels and GcR binding capacity were similar. For testosterone, this agrees with the hypothesis that an adequate
level of this hormone is a prerequisite for improvement in explosive performances. For cortisol, higher GcR binding capacity after 10 weeks of training (with respect to initial values) indicated an upregulation of GcR concomitant with the increase in hormone levels and performances. These findings suggest that the adaptation to training, confirmed by the improvement in performance, is characterized by a high value of GcR binding capacity and that it is mediated, among other factors, by the hormone levels and up-regulation of the receptors
Inflammatory cells and cytokines production in chalazia
No full textPurpose Aim of the present study was to localize the different types of inflammatory
cells and cytokines in chalazion lesions to determine the sequence of events in cellular
reaction.
Methods Fifty four chalazia surgically removed by excision were fixed in Bouin’s solution
and imbedded in paraffin. For immunohistochemical studies we used CD68, CD3,
CD4, CD8, CD45RO, lactoferrin antibodies to detect respectively macrophages, T cells,
T helper, T cytotoxic, mature activated T lymphocytes and neutrophils. For detection
of cytokines we used IFN gamma and TNF alpha antibodies. The EnVision peroxidase
detection system were used and the immmunoreactivity was visualized with diaminobenzidine.
Results Large numbers of macrophages infiltrated the stroma around the alveoli and
the glandular tissue of the chalazion lesions. Lower numbers of the neutrophils were
found with similar distribution to macrophages. CD3(+) lymphocytes also accumulated
in large numbers in the stroma, around the glands, and in the areas of granulomatous
inflammation indicating an association with macrophages and neutrophils. Within the
T-cell population, numerous CD8(+) cells, fewer CD4(+) cells, many CD45RO(+) cells
were present. Positivity for IFN-gamma and TNF-alpha was showed in granulomatous
areas and near vessels.
Conclusion These cells play a significant role in the formation of the chalazion lesion.
Neutrophils might be recruited into granulomatous lesions from the blood and may
subsequently promote inflammatory cells accumulation both by direct cell to cell interactions
and through the interaction of cytokines. The presence of IFN-gamma and TNF
alpha suggests that these cytokines play a paracrine role in chalazion inflammatio
Endothelin-1 and endothelin-converting enzyme-1 in chalazia
No full textPurpose Foreign body giant cells, lymphocytes, plasma cells, and polymorphonuclear leukocytes are present within the lipogranuloma of chalazion. The aim of the present study was to investigate possible local endothelin-1 (ET-1) production by inflammatory cells and ET-converting enzyme-1 (ECE-1) expression in chalazion lesions.
Methods Forty chalazia removed surgically by excision from suffering patients were studied. Chalazia were fixed in Bouin’s or formalin solution and embedded in paraffin. Chalazia sections were stained with hematoxylin and eosin for histological examination and incubated with specific antiserum for ET-1 and ECE-1 for the immunohistochemical technique. The EnVision peroxidase detection system was used and the immunoreactivity was visualized with 3-amino-9-ethylcarbazole (AEC) as a substrate. Negative controls were carried out omitting primary antibody.
Results Histological analysis was carried out on chalazia at different stages of development, particularly chalazia with inflammatory cells or granulomatous structures. The epithelium of central duct and the alveoli did not immunostain for ET-1. Instead, ET-1 positive cells, specially neutrophils and macrophages were located in the stroma, around the alveoli, and within the lipogranuloma. The ECE-1 is present strongly in epithelial cells of ducts and scarcely in the secreting portion of the glands, suggesting a local ET-1 production by inflammatory cells.
Conclusions Thus, the ET-1 and the putative presence of ET- receptors on neutrophils oe macrophages may provide a local source of ET-1 which might act in an autocrine/paracrine role to support granulomatous structures
High Doses of Ascorbate Kill Y79 Retinoblastoma Cells In vitro
Get PDFObjectives: To tests the sensitivity of Y79 retinoblastoma cell lines to high doses of ascorbate, in vitro, and compare
its effects with those of some chemotherapeutic agents routinely employed in the treatment of retinoblastoma.
Methods: Y79 retinoblastoma cells have been exposed to increasing doses of either sodium ascorbate (SA) or
Melphalan (MEL), to define a dose-response curve around the peak plasma concentrations reached by both chemicals
when administered according to the existing therapeutic procedures and protocols. The assessment of cell number and
viability was performed, before and after exposure, with both the manual (Trypan Blue Exclusion Test) and automated
(flow cytometry) methods. Fluorescence microscopy and direct observation of cells in culture, with inverted microscope,
were also performed.
Results: Y79 cells are highly sensitive to the cytotoxic effect of SA, with cell viability reduced of over 90% in some
experiments. As reported in the literature, this effect is directly cytotoxic and most probably mediated by acute oxidative
stress on different cellular components. The same does not apply to Melphalan which, at the doses commonly used for
therapeutic purposes, did not show any significant effect on cell viability, in vitro.
Conclusion: To our knowledge, this is the first report showing that high doses of SA can actively kill retinoblastoma
cells in vitro. While it is not surprising for SA, to show direct cytotoxic effect on tumor cells, the data reported herein
represent the first evidence in favor of the possible clinical use of high doses of intravenous SA, to treat children
affected by retinoblastoma. Given the many advantages of SA over the chemotherapeutic agents commonly employed
to treat cancer (including its almost total absence of toxic or side effects, and its exclusive specificity for cancer cells),
it is reasonable to assume, from the data reported herein, that the high doses of intravenous ascorbate, have the
potential to represent a real revolution in the treatment of retinoblastoma
Megadoses of Ascorbate as a New Chemotherapeutic Approach in Uveal Melanoma: A Preliminary In Vitro Investigation
Get PDFBackground: Despite the more recent advances, there is still no effective systemic therapy for Uveal Melanoma (UM). However, a better understanding of the role of oxidative stress in cancer, has more recently led to a completely new approach to the systemic therapy of cancer, and modulators of the oxidative balance, such as sodium ascorbate (ASC) or arsenic trioxide (ATO), have already entered advanced phases of preclinical and clinical development.
Since high doses of ASC have already demonstrated a strong cytotoxic effect on different human cancer cell lines, we have undertaken the present investigation in order to test the sensitivity of OCM1 and C918 uveal melanoma (UM) cell lines to high doses of ASC, in vitro, as compared to ATO, a pro-oxidant drug which has already undergone extensive in vitro and pre-clinical investigation in UM.
Methods: Both OCM1 and C918 UM cell lines have been exposed to increasing doses of either ASC or ATO, to build a dose-response curve around the peak plasma concentrations reached by both chemicals. The assessment of cell count and viability was performed with flow cytometry.
Results: Both OCM1 and C918 UM cell lines are highly sensitive to ASC in the range of millimolar (mM) concentrations which can be usually reached by the intravenous injection of high doses of the compound. ATO at the dosages used in this study, never reached the LC50. When the exposure to ASC was reduced to two hours, it still had significant effects on survival of both OCM1 and C918 UM cells.
Conclusions: This report shows that ASC is highly cytotoxic for both OCM1 and C918 UM cells, when used in high, pro-oxidant doses. To our knowledge, this is the first report showing that UM cells can be efficiently killed, in vitro, with high doses of ASC
Megadoses of Sodium Ascorbate Efficiently Kill HL60 Cells <i>in Vitro</i>: Comparison with Arsenic Trioxide
No full textArsenic Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce differentiation or kill APL and other tumor cells according to the dosage. Part of the cytotoxic effects of ATO on APL cells is due to its pro-oxidant activity, a characteristic which ATO shares with a number of other compounds, including high doses of ascorbate (ASC). In a comparative investigation on the cy-totoxic effects of both ATO and ASC on HL60 (APL) cell lines, in vitro, we have been able to confirm the known cy-totoxic effects of ATO, but, more importantly, we have demonstrated that ASC is significantly more effective than ATO, in killing these cancer cells in vitro, when the concentrations are maintained within the millimolar (mM) range, i.e. the range of plasma concentrations at which ASC induces oxidative damage to tumor cells. Since these plasma lev- els can be reached only by the intravenous administration of high doses of ASC, we propose that intravenous high doses of ASC may represent a potentially revolutionary new approach in the management of APL
ENDOTHELIN-CONVERCTING ENZYME-1 (ece-1) EXPRESSION AND LYMPHATIC VESSELS DISTRIBUTION IN HUMAN COLORECTAL CANCER.
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Gastrointestinal Conditions Affect Chronic Pain and Quality of Life in Women
Get PDFPain is a chronic condition in many women; drugs used for its treatment are often accompanied by detrimental effects on many organs, including the gut. Once inflamed, the gut can affect pain processes. The aim of this study was to evaluate the general health of women suffering chronic pain, with particular attention to gastrointestinal (GI) conditions. The possibility to improve pain and quality of life through personalized nutritional advice was also tested. Forty women suffering from chronic pain were contacted for the administration of questionnaires to define their pain features and gastrointestinal conditions. Their psychological, clinical and reproductive states were also recorded. Pain scores were correlated with GI, psychological and clinical scores. Diet suggestions were given, and evaluation was repeated after 4 weeks. Thirty-eight women were included in the study: 32 suffered chronic widespread pain and had 6 pelvic pain. Pain had been present in all women for years; more than 80% of women reported various types of disorders related to the gut. Pain scores were worse in the women intolerant to milk and dairy products. The GI score was positively correlated with the pain score. The Dietary Inflammatory Index was very high in all subjects. Personalized nutritional advice followed by 26 subjects for 4 weeks resulted in a significant improvement of pain and quality of life parameters. We describe women with chronic pain as being particularly affected by GI alterations. The change in feeding habits had a beneficial effect on pain and other quality of life parameters
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