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S Barni

Publications and source records attributed to S Barni.

At least 217 records · Page 12Linked to original sources

Effects of isoprenaline treatment on the rat liver parenchyma. Ultrastructural investigations.

Ultrastructural modifications of liver cells were studied in adult rats treated with high doses of isoprenaline for 8 days and subsequently sacrificed at various times up to 25 days from the beginning of treatment. The most evident changes were observed at the earliest times after the end of treatment. They involved both the nucleus (changes in shape and chromatin organization) and cytoplasmic organelles such as the rough endoplasmic reticulum and the smooth endoplasmic reticulum, the latter exhibiting marked dilation and increase, while glycogen generally appeared to be decreased. At later times after the end of treatment, these changes tended to disappear, while there was an increase of peroxisomes and particularly of lysosomes, which exhibited a clearly polymorphic pattern.

Animals↗

Ultrastructural cytochemical investigations on adenyl cyclase activity in isoprenaline-treated rat liver.

The possibility to demonstrate with cytochemical methods (REIK et al. 1970, HOWELL and WHITFIELD 1972) the activity of adenyl cyclase in rat liver following isoprenaline (IPR) stimulation was evaluated. The drug proved effective as an activator of the enzyme, particularly after in vivo treatment for several days, since it led to the formation of many precipitates which could be ascribed to adenyl cyclase activity, mainly on hepatocyte plasma membranes facing sinusoidal areas. The findings obtained during the experiment, through consistent with the hypothesis of a stimulation of hepatic adenyl cyclase by IPR, pointed out some limitations of the cytochemical techniques now available.

Adenylyl Cyclases↗

Failures (cause and time) of radiotherapy in oral cancer.

The results of retrospective clinical evaluation concerning 434 cases of oral carcinomas treated with radiotherapy from January 1959 to December 1967 are presented. The analysis of the results obtained shows that radiotherapy alone may offer a reasonable possiblity of success in limited lesions (68.3% 5-year survival of Stage I patients). In more advanced local cases, and especially those with regional adenopathies, radiotherapy alone cannot consistently control the disease for a long period of time; 5-year survival from the onset of treatment was respectively 36.5% and 24.5% for Stage II and III cases. Moreover, if controlateral of bilateral metastatic adenopathies or fixed lymph nodes are present, the prognosis becomes dramatic (2.6% 5-year survival of Stage IV patients). Among the irradiation techniques currently available, curietherapy (intersitial applications or surface molds) presumably offers the best possibility of success, since the observed failures, both overall and stage by stage, are inferior. Radiotherapy alone may generally be of proven efficacy if the local or locoregional extension is limited. In more advanced cases a combined surgery-chemotherapy treatment method is recommended. The criteria for a combined therapeutic approach for these tumors are also discussed.

Aged↗

Glycogen changes in the liver cells of young rats following isoprenaline treatment. (Histochemical and ultrastructural investigations).

Glycogen changes were investigated by light and electron microscopy in the liver cells of newborn rats following isoprenaline (IPR) treatment either for 1 day (2 intraperitoneal injections at 12 h interval), or for 8 days (2 intraperitoneal injections daily). On the day following the interruption of both treatments glycogen depletion was observed as compared to control rats, as evaluated by PAS reaction and confirmed by higher total phosphorylase activity. During this stage electron microscopy revealed mainly alpha-particles of glycogen associated to highly dilated smooth endoplasmic reticulum (SER) after 1-day-treatment, and to mostly increased SER after prolonged treatment. In the animals submitted to prolonged IPR administration and sacrificed at later times, glycogen masses intensely PAS-positive were strongly increased, while the activity of total phosphorylase proved accordingly lower than in the rats sacrificed at earlier times. Electron microscopy examination confirmed an increased amount of glycogen (alpha- and beta-particles) differently distributed: beta-particles were more numerous in the liver of the rats sacrificed on the last day of the experiment. At this time SER didn't appear modified as compared to control rats.

Animals↗

Changes in liver cells ploidy of young rats following isoprenaline treatment.

Cell proliferation induced by isoprenaline (IPR) stimulation in very high doses was assayed in the liver of young rats, and the formation of polyploid cells was studied form the 15th to the 70th day of life. A general stimulatory effect on a complex process of cellular multiplication, leading to a population of tetraploid cells, was found to be accelerated; the earlier appearance of binucleate cells and the subsequent significant variations in their incidence confirmed the role of this cell type as an intermediate step in the process of polyploidization. Evidence was found of concomitant size changes of the hepatocytes, which might be partially independent of the effect of DNA content. The stimulation was no longer evident 20--30 days from the end of treatment, by when the cells which had come into contact with IPR should have completed the whole sequence of events leading to the formation of tetraploid mononucleate cells.

Animals↗

Modifications in some rat liver cell components following stimulation with isoprenaline (a cytospectrophotometric, microrefractometric and cytoelectrophoretic study).

The liver cell is a quite interesting model for the study of several cytophysiological problems. Proper suspensions of isolated liver cells can be obtained which can be conveniently studied by means of quantitative microtechniques. Several cytochemical and cytophysical techniques (cytospectrophotometry, microrefractometry, and cytoelectrophoresis) were employed for elucidating the effects on the stimulation of the liver cell with high doses of isoprenaline, an amine which is known to produce hypertrophy and hyperplasia in various organs with effects also at the genetic and metabolic level. The following data were collected during the postnatal development of rats up to the 70th day of life: 1) DNA content per nucleus; 2) total dry mass per cell; 3) cellular electrophoretic mobility in connection with the sialomucinic component of the membrane. The process of polyploidization of the liver cell (typical of this life period) was generally accelerated; in this connection, an early appearance of binucleate cells and subsequent significative variations in their incidence were observed. This fact is important as the binucleate cells should represent an alternative intermediate step in the polyploidization phenomenon. At the same time, marked, although transient, signs of cellular hypertrophy were detected during a rearrangement of the hepatocyte dry mass, where the values tended to a multimodal distribution; in particular, IPR appeared to favor the disappearance of cells with a lower mass to the advantage of those with an intermediate mass. The study of electrophoretic mobility evidenced the role of the sialomucinic component of the membrane in the changes occuring in the parenchyma: indeed, this component exhibited an increase, thus causing an acceleration of the mobility similar to the one observed in actively proliferating cell populations. Such change persists even long after the IPR stimulus has ended and, at any rate, beyond the immediate phase of DNA synthesis and the appearance of binucleate cells.

Animals↗

[Changes in the electrokinetic characteristics of hepatic cells in young rats after treatment with isoprenaline].

The changes of the charge group density on the cell membrane and the role of the sialic acid residues were studied in the liver cells of rats treated with high doses of isoprenaline in various organs with effects at genetic, structural and metabolic level. The postnatal growth of the rat liver was followed, when a process of polyploidization occurs: IPR treatment in this period is known to accelerate the phenomenon. IPR was injected twice a day intraperitoneally at the dose of 2 mg/100 g of body weight in one or two week courses. The charge group density was evaluated from the electrophoretic mobility pattern of isolated hepatocytes using the Zeiss cell electrophoresis apparatus. The presence and the importance of sialosubstances in the cell membrane was evaluated by comparing the data from normal cells with neuraminidase treated cells; in this situation, the release of sialic acid by neuraminidase produced significant reductions of the cellular electrophoretic mobility. A general increase of the surface charge density, mostly due to the sialic acid fraction, was demonstrated in association with the IPR treatment; this effect was more evident at later times after the end of the stimulation and in animals treated with two courses of IPR. This study evidenced the role of the membrane sialomucinic component during the whole sequence of events induced by IPR treatment at cytological level and leading, among other things, to a mitotic stimulation. In addition, the persistence of the high charge group density should be taken into account even in connection with cell growth, differentiation and hypertrophy.

Animals↗

A study of the mechanisms involved in the immunostimulatory action of the pineal hormone in cancer patients.

The mechanisms responsible for the immunostimulatory role of the pineal hormone melatonin (MLT) are still obscure. To investigate the influence of MLT on interleukin-2 (IL-2)-induced immune effects in cancer, we compared the results obtained in 14 cancer patients treated with IL-2 (6 x 10(6) IU/day s.c. for 5 days/week for 4 weeks) plus MLT (10 mg/day orally) with those seen in 14 patients treated with IL-2 alone and with those obtained from 14 other patients treated with MLT only. All patients were affected by metastatic solid neoplasms. The increase in the mean number of lymphocytes, T lymphocytes, natural killer cells, CD25-positive cells and eosinophils was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. On the contrary, the increase in mean serum levels of the macrophage marker neopterin was significantly higher in patients treated with IL-2 alone than in those treated with IL-2 plus MLT. Finally, MLT alone has no significant effect on immune cell mean number and on neopterin secretion. These results would suggest that the immunostimulatory action of MLT requires the concomitant presence of IL-2 and that two of the main target cells for MLT activity in humans are represented by T helper lymphocytes of type 2, which are involved in IL-2-induced eosinophilia by the release of IL-5, and macrophages, which may inhibit IL-2-dependent immune functions.

Adjuvants, Immunologic↗

Prognostic factors of the clinical response to subcutaneous immunotherapy with interleukin-2 alone in patients with metastatic renal cell carcinoma.

The intravenous immunotherapy with interleukin 2 (IL-2) represents one of the most active therapies of metastatic renal cell carcinoma (RCC). Recently, it has been demonstrated that IL-2 given subcutaneously in association with interferon alpha (IFN) may determine a response rate in RCC comparable to that obtained with an intravenous route of administration, but with a lower toxicity. Moreover, our previous data have suggested that IFN is not essential for IL-2 efficacy. On the basis of these data, we have designed a protocol of immunotherapy with IL-2 alone given subcutaneously in the treatment of metastatic RCC. The study included 48 consecutive evaluable patients. IL-2 was given at a daily dose of 6 million IU for 5 days/week for 6 consecutive weeks, corresponding to one IL-2 cycle. The overall response rate was 14/48 (29%; CR:1; PR:13). Response rate was significantly higher in nephrectomized than in nonnephrectomized patients, and in patients with a good compared to those with a low performance status. Patients with an interval between the diagnosis of primary renal tumor and of its metastases longer than 1 year did better than those with a lower interval, as did patients with a single metastasis compared to those with multiple metastases, while no significant difference was seen in relation to sex, age and previous IFN therapy. As far as dominant metastasis sites are concerned, patients with liver metastases showed a response rate significantly lower than that seen in patients with metastases in sites other than liver. Toxicity was low in all patients. This study shows that the subcutaneous immunotherapy with IL-2 alone is a well tolerated and effective therapy of metastatic RCC. The evidence of a low PS, disseminated tumor and liver metastases represents the most important negative prognostic factor for the response to therapy.

Adult↗

Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone.

Our preliminary studies in humans have shown that the pineal neurohormone melatonin (MLT) may enhance the antitumor activity of IL-2, by confirming the existence of a neuroendocrine control on cytokine effects. On this basis, a study was started to evaluate the influence of a concomitant administration of MLT and low-dose IL-2 in cancer patients, who had progressed during a previous immunotherapy with IL-2 alone. The study included 14 patients with advanced solid tumors (lung 6; kidney 4; stomach 2; liver 1; melanoma 1). IL-2 was given at a daily dose of 3 million IU s.c. for 6 days/week for 4 weeks. MLT was given orally at a daily dose of 40 mg every day, starting 7 days prior to IL-2. Objective tumor regression, consisting of a partial remission (PR), was achieved in 3/14 (21%) patients (lung 1; kidney 1; liver 1). Six other patients had a stable disease (SD), while the remaining 5 cases progressed. PR and SD were associated either with a significantly longer survival at 1 year, or with a significantly higher increase in lymphocyte and eosinophil mean number with respect to the patients with disease progression. This preliminary study suggests that advanced solid neoplasms resistant to IL-2 may become responsive to IL-2 therapy by a concomitant administration of the pineal hormone MLT, which could act by enhancing IL-2 antitumor immune effect and/or by increasing the susceptibility of cancer cells to the cytolysis mediated by IL-2-induced cytotoxic lymphocytes.

Aged↗

Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors.

Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in association with the pineal hormone MLT may constitute a new well-tolerated and potentially active therapy of untreatable advanced endocrine tumors.

Abdominal Neoplasms↗