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L Pacchiarini

Publications and source records attributed to L Pacchiarini.

35 records · Page 2Linked to original sources

[Invagination of a gastric leiomyoma causing duodenal subocclusion and cholestasis].

The case is reported of a 78 year old female admitted to our Department with symptoms compatible with intestinal obstruction and melena. Upper gastrointestinal x-ray examination and endoscopy did not lead to a precise diagnosis. On the contrary, double contrast x-ray examination revealed the presence of a probably benign gastric tumour with gastroduodenal intussusception. Cholestasis was also present, as suggested by elevated serum conjugated bilirubin levels and by intravenous cholangiography. These findings were confirmed during surgical operation; a partial gastrectomy with gastroentero anastomosis was performed; histologic examination showed that the tumour was a gastric leiomyoma. All the symptoms disappeared quickly and the patient is still in good health after 2 years.

Aged↗

Activation of platelet prostaglandin biosynthesis pathway during neoplastic cell-induced platelet aggregation.

In a previous study we found a correlation between metastatic potential and platelet aggregating activity in sublines of a benzopyrene-induced murine fibrosarcoma ( mFS6 ); the purpose of the present work was to elucidate the role of thromboxane biosynthesis by platelets and/or by neoplastic cells in the activation of platelets in this system. The cells of the more malignant subline induced higher aggregation and TxB2 production than those of the non metastasizing one. The supernatants of aggregating cell suspensions contained very few TxB2; furthermore, preincubation of platelets with ASA or Apyrase resulted in inhibition of aggregation and TxB2 production, while preincubation of the cells was ineffective; these results suggest the platelet origin of the measured TxB2 and indicate that platelet-derived ADP plays an important role in their activation, while the production of ADP by the cells does not seem to be relevant in this model. The involvement of platelet prostaglandin biosynthesis pathway in neoplastic cell induced platelet activation could play an important role in the development of platelet-dependent tumour metastasis.

Animals↗

Interactions between neoplastic cells with different metastasizing capacity and platelet function.

We have examined the effects on platelet function of two sublines (M4 and M9) derived from spontaneous lung nodules of a benzopyrene-induced murine fibrosarcoma (m FS6). The subline M4 was more metastatic and the subline M9 less metastatic than the primary tumour. Only the more malignant cells were able to induce irreversible aggregation of human platelets; this effect was concentration-dependent and was associated with the release of serotonin by platelets. Both aggregation and release were inhibited by preincubation of platelets with ASA, not by preincubation of the cells. The supernatants of cell suspensions had no aggregating activity. However, the neoplastic cells in culture media released an activity directly stimulating platelet aggregation and potentiating the platelet response to ADP; again, this activity was higher for the more malignant cells and the effects were inhibited by preincubation of platelets with ASA. These results suggest a role for platelets in the development of tumour metastases.

Adenosine Diphosphate↗

[In vitro effect of culture fluids from neoplastic tissues on platelet aggregation. I. Human tumors of the gastrointestinal tract].

The effects on platelet function of culture media from 7 human tumours of the gastroenteric tract have been studied on platelet rich plasma obtained from 28 apparently normal subjects. Platelet aggregation was investigated according to Born's method. Some of the culture media showed an aggregating activity on platelets, while others did not; after dialysis, however, also the last ones aggregated platelets. Furthermore all the media both before and after dialysis were able to increase the platelet response to low doses of ADP (3 microM), and these effects were inhibited by Aspirin (0,1 mM). These results suggest that the tumours investigated release stimulating activities on platelet function and that these interactions can be inhibited pharmacologically.

Adenosine Diphosphate↗

[In vitro effect of culture fluids from neoplastic tissues on platelet aggregation. II. Experimental tumors].

We have investigated the effects on platelet function of culture media from 2 sublines of a benzopyrene-induced murine sarcoma (mFS6). Platelet aggregation was investigated according to Born's method. The cell line with greater "in vivo" invasiveness showed higher aggregating activity and higher increase on ADP-induced aggregation; these effects were inhibited by the preincubation of platelets with Aspirin (0,1 mM). These results suggest the role of platelets in metastasis formation; the possibility to inhibit pharmacologically the interactions between platelets and tumour cells could have important implications from both speculative and practical viewpoints.

Adenosine Diphosphate↗

Enhanced antithrombotic mechanisms in patients with maturity-onset diabetes mellitus without thromboembolic complications.

Some haemostatic parameters have been evaluated in a group of rigorously selected patients with maturity-onset diabetes mellitus without thromboembolic complications and in apparently normal subjects of the same age before and after the venous occlusion test (VOT). In basal conditions diabetics had higher levels of AT III as biological activity and higher fibrinolytic and antifibrinolytic activities than controls. After VOT, F VIII R:Ag increased significantly in both groups, more markedly in controls than in diabetics, while F VIII: C showed no modification. Also AT III R:Ag increased after the test, but such variation was significant only in diabetics; on the contrary, the biological activity of AT III was always significantly decreased after the test. After VOT there were also in both groups highly significant increases in the fibrinolytic and antifibrinolytic activities. Finally, HbA1c levels directly correlated with AT III as biological activity before VOT, but with no other parameter either before or after the test. These data suggest the existence in patients with diabetes mellitus without thromboembolic complications of an activated protective mechanism against intravascular clotting.

Aged↗

Antithrombin III biological activity and emotional stress in patients with coronary artery disease.

We studied the effect of emotional stress (mental arithmetic for 10 minutes) in ten postinfarction patients and in ten age-matched, apparently healthy subjects as controls. Blood samples for the determination of epinephrine and AT III levels were taken in basal conditions, at the end of mental stress and after 30 minutes of recovery. Mental stress induced a significant increase in epinephrine levels and a significant decrease in AT III levels in control subjects. Both parameters returned to baseline values after 30 minutes of recovery. On the contrary, in postinfarction patients AT III levels of recovery were still significantly lower than those of baseline, suggesting a reduced ability to restore the original concentration of this physiologic inhibitor. Our data can contribute to a better understanding of the complex relationships among phychosocial factors, the haemostatic system and vascular disease.

Adult↗

Proaggregating and procoagulant activities of human mesothelioma tumor cells at different stages of "in vitro" culture.

BACKGROUND: The mechanisms of the interactions between tumor cells and the hemostatic system are not completely understood; the purpose of this study was to elucidate whether tumor cells grown "in vitro" express the same proaggregating and procoagulant activities as cells isolated from tumor tissues, and whether the activities of such cultures are constant and consistent over time. METHODS: Tumor cells were collected and cultured from the pleural fluid of a 71-year-old patient with a sarcomatous malignant mesothelioma. Platelet aggregating activity was studied by adding tumor cells to platelet rich plasma or to washed, aequorin-loaded platelets. The procoagulant activity of the tumor cells was measured by the one-stage recalcification time of different humans plasma substrates. RESULTS: Cells harvested after 4 culture passages possessed low, ADP-dependent platelet aggregating activity, while those studied after 16 or 40 passages activated platelets through the production of thrombin. In the washed platelet system and in the presence of trace amounts of platelet poor plasma, the difference in the aggregating activity of various tumor cell populations was more evident. Normal mesothelial cells did not induce platelet aggregation. Procoagulant activity (tissue factor-like) was low in normal mesothelial cells and in tumor cells after 4 passages, and it was about 10 times higher in tumor cells after 16 or 40 passages. CONCLUSIONS: Results obtained with tumor cells cultured "in vitro" should be considered with caution because their effects are different from those of freshly isolated cells and may not be constant in the different culture passages.

Adult↗

Human tumor cells cultured "in vitro" activate platelet function by producing ADP or thrombin.

We studied the effects on platelet function of different human tumour cells cultured "in vitro": Mo T lymphocyte cell line, NCI-N592 small cell lung carcinoma cell line, and 5637 bladder carcinoma cell line. Mo and NCI-N592 cells possessed a slight, dose-dependent platelet aggregating activity, which was completely abolished by apyrase and unaffected by hirudin. The cell-free supernatant also induced an aggregation response, which was very similar to that obtained with tumour cell suspensions. The presence of ADP in the cell-free supernatants of cell suspensions was confirmed by HPLC analysis. On the contrary, aggregation induced by 5637 cells was preceded by a significant lag phase; it was not affected by apyrase but it was abolished by hirudin, and the cell-free supernatant had no effect. These data suggest that Mo and NCI-N592 cells activate platelets by producing ADP, while 5637 cells stimulate platelet function by generating thrombin. The amount of ADP produced by the first two tumour cell lines was measured by bioassay: the extent of such production was similar for both cell lines and the maximum was reached after 60 minutes and maintained for up to 3 hours. These results suggest that neoplastic cells can activate platelets by different mechanisms: such investigations should be performed in homologous systems and in well-defined experimental conditions.

Adenosine Diphosphate↗

Effect of interferon alpha, interferon gamma and tumor necrosis factor on the procoagulant activity of human cancer cells.

BACKGROUND: It is not known whether the different cytokines may influence the procoagulant activity of cancer cells; the purpose of this study was to investigate the effect of interferon alpha, interferon gamma and tumor necrosis factor on the procoagulation capacity of human cancer cells cultured "in vitro" or isolated from tumor tissues. METHODS: "In vitro" cultured tumor cell lines were derived from a patient with malignant mesothelioma and a patient with lung adenocarcinoma. Cells isolated from 6 carcinomas of different origin were also investigated. The procoagulant activity of the cells before and after treatment with the cytokines was expressed as RBT U/10(5) cells or RVV U/10(5) cells. RESULTS: Short-term incubation of tumor cells cultured "in vitro" with cytokines did not modify their procoagulant activity; after longer incubation however, interferon alpha induced a significant increase in the procoagulant activity of mesothelioma cells, while interferon gamma induced and increase in the procoagulant activity of lung adenocarcinoma cells. Furthermore, short-term incubation of cells isolated from tumor tissues with interferon gamma or tumor necrosis factor resulted in a significant increase of procoagulant activity, while interferon alpha had no effect. CONCLUSIONS: Altogether, these data demonstrate that the cytokines may influence the expression of the different procoagulant activities of tumor cells.

Blood Coagulation↗

Cryopreservation of human platelets using dimethyl sulfoxide and glycerol-glucose: effects on "in vitro" platelet function.

BACKGROUND: The technique of freezing blood platelets could be very useful in the transfusion support of thrombocytopenic patients. The best method of platelet cryopreservation still remains an object of debate, though it has been suggested that dimethyl sulfoxide (DMSO) is more effective than glycerol-glucose as a cryopreservative. However, few studies have directly compared platelets cryopreserved with different methods. METHODS: We compared "in vitro" function of platelets cryopreserved with 5% dimethyl sulfoxide (DMSO) or 3% glycerol-glucose at -140 degrees C. Platelet aggregation and release reaction were studied with a Lumi aggregometer, thromboxane B2 (TxB2) production by radioimmunoassay, and Ca++ movement by the Fura 2 method. RESULTS: Cryopreservation with both of the methods dramatically reduced the ability of platelets to release ATP and to aggregate in response to single agonists. In contrast, cryopreserved platelets maintained their ability to aggregate after stimulation with paired agonists and to produce TxB2. Cytoplasmic Ca++ increase induced by thrombin was observed in the glycerol-preserved platelets, while it was nearly absent in the DMSO-preserved ones. CONCLUSIONS: We suggest that cryopreservation with glycerol-glucose or DMSO induces similar defects of platelet function. The damage is severe, but platelets are still able to respond to strong stimulation.

Blood Platelets↗

In vitro effect of reduced glutathione on platelet function.

BACKGROUND: Generation of reactive oxygen species has been suggested to represent an important regulatory mechanism of platelet reactivity in both physiological and pathological conditions, and free-radical scavengers may inhibit platelet activation. The purpose of the present study was to investigate the effect of reduced glutathione (GSH) on different platelet functions stimulated by ADP, collagen or PAF. METHODS: Platelet aggregation was investigated by Born's method. TxB2 and PDGF levels were measured by radioimmunoassay. RESULTS: GSH at the lowest dose (1 mM) did not significantly modify aggregation, TxB2 production or PDGF release induced by ADP or PAF, while at higher concentrations (3 mM or 10 mM) it significantly inhibited all parameters. Collagen-induced platelet activation was remarkably less sensitive to GSH, since aggregation was not significantly reduced, while TxB2 production was reduced by GSH when employed at concentrations of 3 mM or 10 mM, and PDGF release was inhibited only by the highest dose (10 mM). IC50 for inhibition of platelet aggregation, TxB2 production and PDGF release were between 1.43 and 2.36 mM when platelets were stimulated with ADP, between 2.23 and 8.90 mM when PAF was used and between 8.00 and 16.30 mM when collagen was the agonist. CONCLUSIONS: Our data suggest that GSH may act as a physiological inhibitor of platelet activation and may therefore contribute to the regulation of platelet reactivity.

Adenosine Diphosphate↗