Search PubMed⌕ Search

Biomedical subjects

I Nicoletti

Publications and source records attributed to I Nicoletti.

At least 73 records · Page 4Linked to original sources
PubMed1992

Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death.

Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca(++)ionophore-induced apoptosis.

Adjuvants, Immunologic↗
PubMed1991

A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.

Corticosteroids, calcium ionophores and anti-CD3 monoclonal antibodies kill mouse thymocytes incubated in vitro. Cell death is preceded by extensive DNA fragmentation into oligonucleosomal subunits. This type of cell death (apoptosis), which physiologically occurs in the intrathymic process of immune cell selection, is usually evaluated by either electrophoretic or colorimetric methods which measure DNA fragmentation in the nuclear extracts. These techniques are unable to determine the percentage of apoptotic nuclei or recognize the apoptotic cells in a heterogeneous cell population. We have developed a flow cytometric method for measuring the percentage of apoptotic nuclei after propidium iodide staining in hypotonic buffer and have compared it with the classical colorimetric and electrophoretic techniques using dexamethasone (DEX)-treated mouse thymocytes. Apoptotic nuclei appeared as a broad hypodiploid DNA peak which was easily discriminable from the narrow peak of thymocytes with normal (diploid) DNA content in the red fluorescence channels. When the DEX-induced apoptosis was inhibited by either low-temperature (4 degrees C) incubation or cycloheximide treatment, no hypodiploid DNA peak appeared. Similarly, thymocyte death induced by sodium azide, a substance with cell-killing activity through non-apoptotic mechanisms, did not result in any variation in the normal DNA peak. The flow cytometric data showed an excellent correlation with the results obtained with both electrophoretic and colorimetric methods. This new rapid, simple and reproducible method should prove useful for assessing apoptosis of specific cell populations in heterogeneous tissues such as bone marrow, thymus and lymph nodes.

Animals↗
PubMed1991

A comparative study on the effects of a monophasic pill containing desogestrel plus 20 micrograms ethinylestradiol, a triphasic combination containing levonorgestrel and a monophasic combination containing gestodene on coagulatory factors.

The changes in haemostasis during oral contraception are related to the ethinylestradiol dose present in the formulation taken by the patient. An open, randomized longitudinal study was performed to evaluate and compare the effects that low-dose oral contraceptives (OCs) containing different doses of ethinylestradiol exert on the haemostatic system. Eighty-nine healthy women, aged 18-45 years, were randomly assigned to treatment with 3 different OCs: a monophasic pill containing 30 micrograms of ethinylestradiol plus 75 micrograms of gestodene (GSD/30) (30 subjects), a triphasic pill containing levonorgestrel (TRI/LNG) (28 subjects), a monophasic pill containing 20 micrograms ethinylestradiol plus 150 micrograms of desogestrel (DOG/20) (31 subjects). From every woman, blood samples were collected before treatment and at the 3rd and 6th cycle of pill intake. The number of platelets significantly increased (p less than 0.01) during treatment with TRI/LNG. Fibrinogen plasma values were significantly increased (p less than 0.05) only in women treated with the preparation GSD/30. Fibrinopeptide A (FPA) plasma levels significantly increased (p less than 0.01) during treatment with the pills TRI/LNG and GSD/30, but the levels of FPA were unchanged in the group treated with DOG/20. The overall results of this study confirm that the effects of OCs on haemostasis are dependent on the ethinylestradiol dose. Moreover, they suggest that with reduction of the ethinylestradiol component to 20 micrograms, the effects of OCs on haemostasis seem to be virtually eliminated.

Adult↗
PubMed1991

Inhibition of human breast cancer cell (MCF-7) growth in vitro by the somatostatin analog SMS 201-995: effects on cell cycle parameters and apoptotic cell death.

Somatostatin (SS) and SS analogs have been shown to exert an antiproliferative effect on several transplantable tumors in animals and to reduce the growth of pancreatic, pituitary, and mammary tumor cells in vitro. We evaluated the effects that the SS analog SMS 201-995 exerts on growth, cell-cycle parameters, and suicidal cell death (apoptosis) of human breast cancer cells (MCF-7) in vitro. SMS 201-995 significantly reduced the MCF-7 cell growth induced by serum, estradiol, insulin, and insulin-like growth Factor-I in both short term and long term experiments. The effect was maximal when 10 nM estradiol was used as mitogen in long term cultures. SMS 201-995 treatment produced a slight but transient accumulation of cells in the G2/M phase but did not cause any noteworthy reduction in the percentage of proliferating cells. There was, instead, a time-related increase in the number of cells with the flow-cytometric characteristics of apoptosis in the cultures treated with the SS analog, which correlated well with its growth-inhibiting activity. It would, therefore, seem that SMS 201-995 exerts its inhibitory effect on MCF-7 cell growth in vitro mainly by enhancing the rate of programmed (or suicidal) cell death in the culture.

Breast Neoplasms↗
PubMed1990

Inhibitory effect of the somatostatin analog octreotide on rat pituitary tumor cell (GH3) proliferation in vitro.

The effects of somatostatin-14 (SS-14) and the somatostatin-analog octreotide (SMS 201-995, Sandostatin) on proliferation of GH3 pituitary tumor cells were investigated in vitro. SMS 201-995 exerted a significant, but transient, inhibition on GH3 cell growth which reached a maximum at 24 h and was no longer detectable at 48 h. The concentration that evoked the strongest inhibitory effect was 10 nM SMS 201-995, while lower and higher doses resulted in a less pronounced effect. The inhibitory effect SMS 201-995 exerted on cell proliferation was associated with a dose- and time-related reduction in both c-myc and c-fos mRNA levels. SS-14 had no noteworthy influence on either cell proliferation or c-myc and c-fos protooncogene expression. These data demonstrate that SS-analogs transiently inhibit pituitary tumor cell proliferation in vitro.

Animals↗
PubMed1989

Thyroid function tests in acute viral hepatitis: relative reduction in serum thyroxine levels due to T4-TBG binding inhibitors in patients with severe liver cell necrosis.

Thyroid function tests were evaluated in 34 patients with acute viral hepatitis (AVH) and in 38 healthy controls (C). As expected, AVH patients displayed a significant increase in T4, rT3 and TBG serum levels with respect to C, while FT4 and TSH concentrations were similar. A positive correlation between TBG and T4 was evident in C, but not in AVH. In this group there was, instead, an inverse correlation between the sum of serum levels of GOT + GPT and T4 concentrations. When AVH patients were divided in "high necrosis" (HN, serum GOT + GPT greater than 2000 UI/l) and "low necrosis" (LN, serum GOT + GPT less than 2000 UI/ml) groups, we found a significant reduction in both T4 and T3 serum concentrations in HN with respect to LN, despite similar levels of TBG, albumin, FT4 and TSH. The hypothesis that thyroid-hormone binding inhibitors (THBI), released during severe liver cell injury, accounted for an impaired serum binding capacity in HN-AVH, was confirmed by the significant increase in FT4/T4 ratio and by the demonstration of THBI activity in pooled sera of these patients, with respect to LN subgroup. Our present finding may clarify the unexplained observation of reduced T4 levels in patients with fulminant hepatitis and the ominous prognostic significance of a "low T4 syndrome" in subjects with severe liver disease and/or other systemic illnesses.

Acute Disease↗
PubMed1989

X-ring Turner's syndrome with combined immunodeficiency and selective gonadotropin defect.

A rare association of chromosomal, immunological and endocrine defects is described in a young woman with short stature, recurrent pulmonary infections and primary amenorrhea. Cytogenetic studies showed a 45, X karyotype in 65% of peripheral blood lymphocytes and 46,Xr(X) (p22q27) karyotype in the remaining 35%. Severe immunodeficiency was revealed by phenotypical and functional studies and a selective gonadotropin defect was disclosed by endocrinological investigations. An attempt is made to explain the coexistence of the three abnormal pictures.

Adult↗
PubMed1989

Defective natural killer cell activity in puerperal hyperprolactinemia.

Prolactin (PRL) influences immune reactivity in animals and in humans and both T-cell abnormalities and reduced natural killer (NK) cell activity have been reported in women with pathological hyperprolactinemia. To investigate further the possible interactions between PRL and the immune system in humans, we analysed T-cell phenotypes and NK cell activity in 15 women with physiological hyperprolactinemia of the puerperium and in 45 age-matched healthy normal cycling women. Puerperal women displayed a normal T-cell phenotype but a significant reduction in the number of Leu-7+ and Leu-11+ cells, associated with a decreased NK cell activity, as measured against K-562 target cells. There was a significant inverse correlation between the raised serum PRL levels and both the number of Leu-7+ cells and NK cell activity. These data confirm an important immunoregulatory role for PRL in humans and suggest a direct inhibitory effect of the chronically raised PRL concentrations on the maturation of NK cells.

Female↗
PubMed1988

Chromatographic and cytogenetic analysis of in vivo metabolites of fluoranthene.

Fluoranthene metabolites in rat serum were analysed by high-performance liquid chromatography (HPLC) with UV and fluorescence detection and compared with in vitro metabolites obtained by incubation with microsomal fraction of rat hepatocytes. In order to resolve very polar fluorescent compounds present in rat serum, a modification of HPLC existing methods for in vitro metabolites separation was necessary. Mutagenic 2,3-dihydrodiol was identified in both in vitro sample and rat serum: this result is in good accord with cytogenetic analysis on rats bone marrow cells, that shows a slight but significant increase of sister chromatide exchanges.

Animals↗
PubMed1988

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea.

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.

Adult↗
PubMed1987

Phenotypic and functional abnormalities of T lymphocytes in pathological hyperprolactinemia.

The phenotype and function of T cells circulating in patients with pathological hyperprolactinemia were analyzed and compared to those in sex- and age-matched control subjects. Two-color immunofluorescence study revealed an increased number of CD4+ TQ1+ cells and the presence of phenotypically immature CD1+ T cells, also exhibiting transferrin surface receptor, in peripheral blood of the hyperprolactinemic patients. After chronic treatment with the dopamine agonist bromocriptine, T-cell abnormalities disappeared. In addition, some untreated patients showed enhanced T-cell suppressor activity in an in vitro pokeweed mitogen-driven B-cell transformation assay. These immunological findings confirm a link between neuroendocrine and immune systems in humans.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Effect of exogenously administered estrogens on luteinizing hormone release in a complete testicular feminization syndrome patient with very low testosterone levels, before and after gonadectomy.

The response of LH to exogenously administered estrogens was evaluated in a 63-year-old patient affected by complete testicular feminization syndrome (CTFS) with very low testosterone (T) levels, before and after gonadectomy. Prior to gonadectomy a durative fall in gonadotropin levels was observed after estrogen administration, without observing of an estrogenic positive feed-back (EPF) from LH. After gonadectomy, following an initial decrement in both gonadotropins, the characteristic. LH peak was seen, 48 h after E2B (Estradiol Benzoate) administration. This observation, together with the very low T levels that we found in this patient, prompted us to construe that absence of EPF in males is not due, as previously believed, to a direct inhibitory action of T or E2, deriving from T aromatization, on the hypothalamus, but by a still unknown gonadal factor. The hypothesis that this factor has a tubular origin is formulated and discussed.

Androgen-Insensitivity Syndrome↗
PubMed1987

Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia.

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine↗
PubMed1987

Thyroid function tests in patients undergoing maintenance dialysis: characterization of the 'low-T4 syndrome' in subjects on regular hemodialysis and continuous ambulatory peritoneal dialysis.

Thyroid function tests were evaluated in 38 patients on regular hemodialysis (HD), in 36 on continuous ambulatory peritoneal dialysis (CAPD) and in 39 healthy controls. A significant reduction in total thyroxine (TT4), total triiodothyronine (TT3), reverse (rT3), and free T4 (fT4) mean levels and normal TSH, free T3, TBG and albumin concentrations was found in both HD and CAPD patients. A 'low-T4 syndrome' (serum T4 less than 5 micrograms/dl) was found in 9 CAPD (25%) and 20 HD (53%) patients, but none of them had fT4 levels below the normal laboratory range. The only striking difference between low-T4 HD and low-T4 CAPD patients was the significantly lower TBG and albumin serum levels in CAPD group. Low-T4 HD displayed normal TBG levels but enhanced fT4/TT4 and fT4/TT4 X TBG ratios. We concluded that: the abnormalities in thyroid function tests in patients on long-term dialysis (HD and CAPD) do not express the existence of a true hypothyroidism; a different pathogenesis of the low-T4 syndrome in the CAPD and HD groups may be hypothesized: in the former it could be attributed to a reduction in serum-binding capacity for thyroid hormones, in the latter the relative increase in fT4 percentage despite normal TBG levels suggests either the presence of T4-TBG-binding inhibitor(s), or structural abnormalities of thyroid-hormone-binding proteins.

Combined Modality Therapy↗