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Biomedical subjects

C Finelli

Publications and source records attributed to C Finelli.

At least 37 records · Page 2Linked to original sources

Effect of glutathione monoethyl ester on glutathione level and cardiac energetics in reperfused pig heart.

The GSH level in myocardial tissue represents an important defense mechanism against oxygen toxicity. Since the ischemia-induced depletion of GSH might favour the cytotoxicity of oxygen-derived free radicals produced during reperfusion, we assessed the effects of the GSH donor, glutathione monoethylester, in anaesthetized pigs subjected to 90 minutes of coronary occlusion followed by 30 minutes reperfusion. The drug was infused intracoronarily at a dose of 1 mg/ml (0.5 ml/min) throughout the experimental period. After coronary occlusion and reperfusion, we found a decrease in GSH, ADP, ATP and phosphocreatine levels in reperfused compared with non-ischemic tissue. Less evident were the differences in mitochondrial function, there being only a reduction in the reperfused tissue of the respiratory control index and state 3 respiration values when pyruvate was used as substrate. The infusion with glutathione monoethylester decreased the depletion of tissue GSH and improved the GSH/GSSG ratio, particularly in the non-ischemic tissue. Moreover, the drug decreased the mitochondrial dysfunction at the level of pyruvate utilization and partially prevented the fall in ATP in the reperfused tissue. This study confirms a possible protective effect of glutathione monoethylester in the prevention of reperfusion-induced myocardial damage.

Adenosine Diphosphate↗

[The role of prostaglandins in fertility. Experimental research].

Prevention of postoperative adhesion is an issue that continues to elude the abdominal and reproductive surgeon. Adhesions seem to be a result of an inflammatory process and it is well known that prostaglandins play an important role in such an event. In an attempt to improve the results of microsurgery, we have tried in this study to examine the effect of local intraperitoneal application of prostaglandins (PGE2 and PGF2 alpha) on adhesion formation in the rat after traumatizing to the uterine horn. Prostaglandins applied locally were found to increase intraperitoneal adhesion formation at the injured sites, in comparison with controls. Also, we have reported on histological examination an increased accumulation of inflammatory cells in traumatized areas. However, we didn't observe a reduced fertility in rats treated with prostaglandins because these substances induce follicular rupture by activation of proteolytic enzyme located in the follicular wall. We conclude that prostaglandins play an important role in the process of adhesion formation. Using antiprostaglandins agents could improve the outcomes of reproductive surgery.

Animals↗

Age-related changes in cardiac mitochondrial energetics under the influence of calcium in rat.

Mitochondria extracted from the hearts of Wistar rats aged 6 and 24 months showed similar values for the respiratory control index (RCI), state 3 oxygen consumption (QO2) and ADP/O measured using glutamate or succinate as substrates; with the exception that the QO2 of the aged rats was lower than that of the young rats in the presence of glutamate. The consumption of O2 induced by 2-oxoglutarate and ADP was similar in both age groups. Concentrations of external free Ca2+ ranging from 0.2 to 0.8 microM produced an increase in O2 consumption and ATP formation in the young mitochondria, with a maximum effect at 0.2 microM external free Ca2+. Little or no change in O2 consumption and ATP formation was evident in aged mitochondria following incubations in concentrations of external free Ca2+ ranging from 0.2 to 0.8 microM. The continuous rate of formation of ATP, measured in the presence of 0.2 microM external free Ca2+ using a luminescence method, confirmed the previous results. This study indicates that the cardiac mitochondrial phosphorylating system of aged rats is poorly sensitive to variations in external free calcium.

Adenosine Triphosphate↗

Splenectomy for patients with myelofibrosis with myeloid metaplasia: pretreatment variables and outcome prediction.

Since according to the early studies, the outcome after splenectomy in the individual patient with myelofibrosis with myeloid metaplasia (MMM) is unpredictable, we assessed retrospectively the pre-intervention characteristics that best predicted adverse events, hematological consequences, and survival in 71 splenectomized MMM patients. The findings indicate that the operative risk of splenectomy for both mortality (8.4%) and morbidity (39.3%) was unpredictable. New hemorrhagic or thrombotic complications occurred in 16.9% of surviving patients and were predicted by age < 50 years, a normal to high platelet count (> 200 x 10(9)/l) and huge splenomegaly (> 16 cm from the costal margin). Massive liver enlargement occurred in 24% of patients and has to be expected in patients splenectomized for transfusion-dependent anemia. Anemia improved substantially in 45% and 52% of patients at 3 months and at 1 year, respectively, and was predicted by severe anemia, low platelet count (< 100 x 10(9)/l) or normal to high white blood cell (WBC) count (> 4 x 10(9)/l). Survival from splenectomy was superior in patients < 45 years with WBC < 10 x 10(9)/l count. An unexpectedly high rate of blastic transformation was observed. It accounted for 42.8% of the deaths. The results suggest trials for prophylactic cytoreductive treatment in young patients and when platelet count is normal to increased. Further study is needed for elucidating the possible role played by splenectomy in inducing blastic transformation.

Adult↗

[A 31P-NMR spectroscopic study of the changes in energy metabolism induced by cardiac ischemia and reperfusion in rats of different ages].

In order to investigate the energetic status of the aged heart during ischemia and reperfusion we perfused female Wistar rats 6, 12 and 24 month old. The hearts were subjected to 15 min of global total ischemia plus 30 min of reperfusion. NMR spectra were collected during the entire experimental period to have the in vivo monitoring of the changes in intracellular pH and intracellular ATP, PCr and Pi contents. In the first 8 min of ischemia the fall of pH was similar in the 3 groups of rats, while at the end of the ischemic period the young rat hearts showed an intracellular pH significantly lower than aged rat hearts. At the end of reperfusion, ATP and PCr contents appeared significantly higher in the adult and aged hearts as compared to the young. The Pi content, on the contrary, was significantly lower in aged than young rat hearts. We suggest that the hearts of adult and aged animals, at the end of reperfusion, showed larger energetic recovery, in our experimental conditions of brief ischemia, than young hearts.

Aging↗

[Microsurgery and laser surgery in conservative operations on the ovary. Experimental research].

In this study we compared two different conservative surgery techniques performed on 12 ovaries of female rabbits: microsurgery and CO2 Laser surgery. After the surgical procedure all the animals were investigated by a Laparotomy to evaluate the post-operative adhesion formation. Histological examinations were performed on 6 ovaries, to evaluate the possible damage to the ovarian parenchyma. We did not find significant differences between the two methods employed, particularly for the adherence formation and the parenchymal thermic damages: no post-operative adhesions were detected respectively in 3 ovaries operated on by microsurgery and 5 by laser surgery; slight adhesions were present in 2 ovaries treated with microsurgery and in 3 with laser surgery; 3 ovaries treated with microsurgery and 2 with laser surgery showed moderate adhesions. Only 2 ovaries treated with microsurgery presented severe adhesions.

Animals↗

[Tubo-ovarian transplantation in the treatment of sterility. Experimental research].

Microsurgical transposition of fallopian tube and ovary has the potential of being an efficient therapeutic treatment in patients with tubal sterility. The Authors present their experience of microsurgical adnexal transplantation in rabbit by two different techniques: the first procedure by microvascular anastomosis of the ovarian vessels, the second one without vascular pedicle. Function is evaluated at various time after grafting by: exploratory laparotomy on day 30 to establish whether circulation to the grafts was still maintained; macroscopic and microscopic examination of ovaries and fallopian tubes. The microvascular techniques prove highly reliable in terms of immediate vascular patency rate but it is disappointing that 50% of the autografts has failed with blocked vessels by day 30. Perhaps this is due to the difficult techniques in anastomosing the ovarian vessels of small caliber. In spite of these outcomes the vascularized autografts were viable and functional after transplantation in contrast with the non-vascularized tubo-ovarian grafts which all failed. This experience encourages to believe that the microsurgical technique could be employed for homograft transplantation in woman with extensive ovarian and tubal damages.

Anastomosis, Surgical↗

Ticlopidine lowers plasma fibrinogen in patients with polycythaemia rubra vera and additional thrombotic risk factors. A double-blind controlled study.

Thirty-seven patients affected by polycythaemia rubra vera (PRV) and with at least one additional thrombotic risk factor (overt vascular disease, diabetes mellitus, treated hypertension, smoking habit, plasma hyperviscosity, hyperfibrinogenemia) were enrolled in a double-blind randomized placebo-controlled study, and 18 were given ticlopidine 250 mg, b.i.d., for 60 days. All the patients had previously been submitted to cytoreduction, and PRV was under control in all cases at the start of the study. During the study, the haematological parameters were controlled every 15 days, and venesection was performed if haematocrit was greater than 46%. Whole blood viscosity, at low and high shear rates, plasma viscosity, and fibrinogen were measured on days 0 and 60. In the ticlopidine group, we recorded a significant 13.14% reduction of the mean fibrinogen level after treatment (390 +/- 63 vs. 449 +/- 97 mg/dl, p less than 0.01). All the other haemorheological parameters were not significantly modified by ticlopidine treatment, nor were there significant modifications recorded in the placebo group. Our study shows that ticlopidine may reduce a probable thrombotic risk factor (hyperfibrinogenemia) in PRV patients.

Aged↗

Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients.

The prognostic value of 12 clinical and haematological parameters, recorded at diagnosis, in myelofibrosis with myeloid metaplasia (MMM) was retrospectively analysed in a consecutive series of 133 patients followed for a minimum of 60 months. Multivariate analysis showed that the following features were associated with a significantly shorter survival: (1) short period of time (less than 13 months) between first symptoms and diagnosis; (2) anaemia (haemoglobin less than 10 g/dl); (3) leucocyte count greater than 12 x 10(9)/l; (4) peripheral blood granulocyte precursors greater than 10%. Age, splenectomy and percentage of peripheral blood metamyelocytes were found significantly to affect survival only from univariate analysis, whereas sex, size of spleen, thrombocytopenia and thrombocytosis were of no prognostic significance. These data suggest that a more intensive chemotherapy might be useful for younger patients with bad prognostic factors at diagnosis.

Adult↗

Changes in myocardial mitochondrial respiration after ligation of the coronary artery in pigs.

After ligation of the left coronary artery, porcine cardiac mitochondria were isolated by homogenizing the tissue and treating the myofibrillar pellet with nagarse. When compared with unligated controls, the ischemic myocardium showed decreases in phosphocreatine (to 41%), ATP (to 56%) and in the mitochondrial respiratory control index (to 69% and 78% as measured with glutamate and succinate respectively). No changes were found in the corresponding P/O ratios. Similar results were obtained upon separation of the mitochondria into two main fractions by a density gradient technique, though only one of these fractions showed a fall in succinate-supported respiration. The results suggest that ischemia decreases the NADH-dehydrogenase activity of cardiac mitochondria.

Adenosine Diphosphate↗

Influence of age on oxidative damage in mitochondria of ischemic and reperfused rat hearts.

Hearts from rats aged 3 months and 24 months respectively were isolated and subjected to a brief ischemia. The extent of myocardial injury, measured by release of creatine phosphokinase into coronary effluents and by developed tension, was greater in the young rats than in the old when compared with their corresponding non-ischemic controls. The amount of peroxidation, measured in the isolated mitochondria using the malondialdehyde method, was also greater in the younger rats. In contrast, when mitochondria from non-ischemic hearts were incubated for 20 minutes in a medium containing FeCl3, NADPH and ADP, known to generate hydroxyl radicals, significant peroxidation (together with a decrease in respiratory control indices) was obtained only from mitochondria isolated from the older rats. If, as the in vitro results suggest, the mitochondria of the old rats are not less sensitive to peroxidative attack, the difference between the effects of ischemia in the two age groups may be due to a lower rate of formation of reactive species of oxygen or to a greater anti-oxidative cytosolic capacity in the hearts of older rats. Alternatively, the overall oxidative stress following ischemia may be due to the effects of different radicals which target different parts of the mitochondrial membrane.

Aging↗

Cyclosporin A in the treatment of CLL associated PRCA and bone marrow hypoplasia.

Three patients (1 PRCA-T-CLL, 1 PRCA-B-CLL, 1 B-CLL aplasia) were treated with cyclosporin A (CS-A). Patient no 1 had relapsed during steroid therapy and the remaining two patients had been resistant to conventional immunosuppression. CS-A produced in all cases a prompt remission (within 1-4 weeks) of bone marrow failure. Mild reversible renal toxicity was the only side-effect noted. CS-A might be tried in every case of CLL-associated bone marrow failure.

Adult↗

Stromal cells in primary myelofibrosis: ultrastructural observations.

The bone marrows of five patients with primary myelofibrosis at different stages of the disease have been studied. In the myelofibrotic bone marrow, associated with "reticulum cells", two other cell types have been identified, namely fibroblast-like and myofibroblast-like reticulum cells, as well as a spectrum of transitional forms. Our findings suggest that reticulum cells may represent a reserve stromal cell pool (i.e. primitive reticulum cells) able to modulate themselves and to transform differently according to functional requirements. Some suggestions regarding the functional significance of fibroblast-like and myofibroblast-like reticulum cells in primary myelofibrosis are suggested.

Biopsy↗

Deficiency of autologous mixed lymphocyte reaction in patients with idiopathic autoimmune hemolytic anemia.

Alterations in the autologous mixed lymphocyte reaction (autologous MLR) have been reported in many autoimmune diseases and in diseases with a derangement of T regulatory function. We have studied autologous MLR in 10 patients with idiopathic autoimmune hemolytic anemia (IAHA). All patients had decreased autologous MLR which averaged 4,106 +/- 1,332 cpm (SEM) compared to 12,153 +/- 4,166 cpm for simultaneously studied controls. A marked decrease in phytohemagglutinin response and an imbalance of T-cell subsets were also observed. These findings suggest a possible abnormality of T immunoregulatory function in IAHA patients.

Adult↗