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Biomedical subjects

G Damia

Publications and source records attributed to G Damia.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cytotoxic activity and mechanism of action of 5-Aza-2'-deoxycytidine in human CML cells.

We investigated the cytotoxic activity and some aspects of the mode of action of 5-aza-2'-deoxycytidine (Aza-dC) in 21 primary cultures of leukemic cells freshly obtained from patients with chronic myeloid leukemia (CML) in blast crisis. The cytotoxic potency of Aza-dC was comparable or even greater than that of 1-beta-D-arabinofuranosylcytosine (Ara-C) in most cases, suggesting that this drug has potential in the therapy of blast crisis of CML. Drug incorporation into DNA was evaluated by exposing leukemic cells simultaneously to 3H-Aza-dC at the concentration of 0.1 micrograms/ml and 14C-thymidine (TdR) used as internal standard. Incorporation of Aza-dC into DNA was detectable in all cases. In 17 samples we evaluated the DNA integrity of leukemic cells exposed to Aza-dC using alkaline elution techniques. The drug caused a detectable amount of DNA alkali labile sites (ALS). DNA-ALS increased in cells exposed to Aza-dC concentrations from 0.1 to 1 microgram/ml but did not further increase at 10 micrograms/ml. A plateau in the levels of DNA-ALS was also seen in human K562 cells exposed to increasing concentrations of Aza-dC from 5 to 10 micrograms/ml, whereas in these cells Aza-dC incorporation into DNA increased with increasing Aza-dC concentrations. Therefore, DNA-ALS caused by Aza-dC are not simply the result of the chemical decomposition of azacytosine molecules incorporated into DNA, but are presumably the result of a saturable DNA repair mechanism (e.g., glycosylases) leading to formation of the apyrimidinic sites.

Antineoplastic Agents↗
PubMed1993

Prolonged independent lung respiratory treatment after single lung transplantation in pulmonary emphysema.

Single lung transplantation (SLT) is now successfully used in patients with severe emphysema. Mechanical imbalance between the native emphysematous and the healthy transplanted lung can be easily managed, unless severe graft failure occurs, leading to acute respiratory failure. Emergency retransplantation has been used in this setting, since the conventional approach to adult respiratory distress syndrome (ARDS) (mechanical ventilation and positive end-expiratory pressure [PEEP]) fails, due to the mechanical discrepancy between the two lungs. We describe two cases of severe graft failure following SLT in emphysema patients that were successfully treated with prolonged independent respiratory treatment. Mechanical ventilation and PEEP were applied to the failing transplanted lung while the native emphysematous lung was maintained on spontaneous breathing to avoid hyperexpansion and barotrauma. The independent lung respiratory treatment lasted 35 and 25 days, respectively: to our knowledge, these are among the longest-lasting independent respiratory treatments reported. The management was simplified by the early use of a double-lumen tracheostomy cannula as an alternative to orotracheal double lumen tube.

Graft Rejection↗
PubMed1993

[Practical device to reduce the tidal volume in mechanical ventilation, for neonatal and pediatric anesthesia].

The authors propose a new device for controlled mechanical ventilation during general anaesthesia in pediatric and neonatal patients. This device can reduce TV delivered by an adult ventilator to small values. The device consists of: a small volume box (about 1.3 1); a disposable breathing circuit composed of a bag to put in the box, connecting tubes, a non rebreathing duckbill valve placed at the endotracheal tube; a monitoring system for pressure and expired volume. The authors tested the device according to ISO Standards. Performance during waveform tests and expiratory resistance agree with ISO request. During volume performance tests the device was able to deliver a minimum TV of 10 ml in all ISO Standard requested sets.

Anesthesia, General↗
PubMed1992

Prevention of acute chemotherapy-induced death in mice by recombinant human interleukin 1: protection from hematological and nonhematological toxicities.

Previous studies have demonstrated that interleukin 1 (IL-1) can protect most mice from the acute lethal toxicity mediated by high doses of radiation and/or some chemotherapeutic drugs. The results presented herein demonstrate that the pretreatment of mice with recombinant human interleukin 1 alpha (rhIL-1 alpha) protects mice from the lethal effects of several myelotoxic chemotherapeutic drugs, including 5-fluorouracil (5FUra), cyclophosphamide, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), and 1,3-bis-(2-chloroethyl)-1-nitrosourea. However, pretreatment with rhIL-1 alpha was not effective against the acute lethal toxicity generated by doxorubicin and cisplatin. The chemoprotective effects appear to be at least partially due to myeloprotection/restoration, since the recovery of myeloid colony-forming units and the total cellularity in the bone marrow and spleen were accelerated in the rhIL-1 alpha-pretreated mice. However, the chemoprotective effects of rhIL-1 alpha are apparently not limited to myeloprotection, since pretreatment with rhIL-1 alpha protects mice against the lethal toxicity of both 5FUra and cyclophosphamide, yet bone marrow transplants rescue mice treated with 5FUra but not those treated with cyclophosphamide. The chemoprotective effects of rhIL-1 alpha may be at least partially indirect, since the efficacy of chemoprotection by rhIL-1 alpha is reduced in athymic mice, and interleukin 6, but not tumor necrosis factor alpha, can substitute for rhIL-1 alpha in chemoprotection from 5FUra.

Animals↗
PubMed1992

Expression of E. coli tag gene encoding 3-methyladenine glycosylase I in NIH-3T3 murine fibroblasts.

NIH-3T3 fibroblasts were co-transfected with pSV2neo and pSG5tag by the calcium-phosphate precipitation method. The stable integration of the tag gene sequence and its transcription was verified by Southern and Northern blot analysis. 3-Methyladenine glycosylase activity in pSG5tag transfected 3T3 cells was approximately 400 times higher than in cells transfected with the control plasmid pSG5 or in the parental cells and was inhibited by 3-methyladenine. Bacterial tag gene can thus be expressed in mammalian cells and the encoded enzyme is functionally active. These transfected cells could serve as an important tool to investigate the importance of the repair of N3-adenine as a mechanism of protection against the mutagenicity and cytotoxicity of alkylating agents.

3T3 Cells↗
PubMed1992

Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice.

The administration of greater than or equal to 5 micrograms interleukin-7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resulted in a greater than 90% reduction in the frequency and total number of single lineage colony-forming unit-culture (CFU-c) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte colonies that could be cultured from the BM, but a fivefold to 15-fold increase in the number of these progenitors that could be cultured from the spleen. All of these effects were reversible with progenitor and white blood cell numbers returning to near normal by day 6. Morphologic analysis of cells obtained from the BM of IL-7-treated mice showed an increase in lymphoid cells. Surface phenotype analysis showed that most of this IL-7-induced increase in lymphocytes was attributable to an increase in immature B cells (B220+, sIg-), while cells expressing the myelomonocytic markers 8C5 and MAC-1 decreased by twofold to threefold. Further studies showed that the administration of IL-7 to mice that had been rendered leukopenic by the injection of cyclophosphamide (Cy) or 5-fluorouracil (5FU) exhibited a more rapid recovery and/or overshoot in their peripheral blood lymphocytes when compared with mice treated with Cy or 5FU alone. These results show that IL-7 can differentially regulate myelopoiesis in the BM and spleen, while stimulating lymphopoiesis.

Animals↗
PubMed1992

Activity of aphidicolin glycinate alone or in combination with cisplatin in a murine ovarian tumor resistant to cisplatin.

Aphidicolin, a reversible inhibitor of DNA polymerase alpha and delta, has recently been reported to reverse the resistance to cisplatin (DDP) of an ovarian cancer cell line. We investigated the pharmacokinetics of aphidicolin in mice and examined its activity either alone or in combination with DDP in the DDP-sensitive M5076 (M5) murine reticular cell sarcoma as well as in a DDP-resistant subline (M5/DDP). The drug was cleared from plasma very rapidly (clearance, 41.6 ml min-1 kg-1), showing a half-life of 15 min. Aphidicolin concentrations in the tumor were approximately 50% of those found in plasma at steady state. Using several dose schedules and continuous infusions we failed to detect significant antitumor activity for aphidicolin glycinate. Potentiation of the activity of DDP by aphidicolin glycinate was moderate in mice bearing M5 tumor as well as in those bearing M5/DDP tumor. These data do not support the possible clinical use of aphidicolin in combination with DDP. However, further studies should be carried out in different tumor models before this possibility is conclusively ruled out.

Animals↗
PubMed1991

Effects of recombinant transforming growth factor-beta 1 on hematologic recovery after treatment of mice with 5-fluorouracil.

Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit bone marrow colony formation after in vitro treatment as well as after in vivo administration to normal mice. These data suggest that TGF-beta might either protect, or further depress, progenitor cell levels in mice exposed to a cell cycle-active drug such as 5-fluorouracil (5FU). rTGF-beta 1 was administered repeatedly by either the i.v. or i.p. routes to mice during the hyperproliferative state of the bone marrow that occurs 7 to 9 days after the i.v. administration of 150 mg/kg 5FU. The formation of both multilineage and the more differentiated (CFU-c) colonies was inhibited by 20 to 40%/culture, and 66 to 93%/mouse. When multiple doses of rTGF-beta 1 were administered systemically immediately before the injection of 5FU, the resulting rebound in the number of CFU-c and multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage colonies per culture was markedly inhibited by 30 to 77%, whereas the total number of CFU per mouse was inhibited up to 93%. This effect was maximal when rTGF-beta 1 was administered at daily doses of greater than or equal to 5 micrograms/mouse for at least 3 days. This inhibition of the recovery of the bone marrow from 5FU treatment induced by rTGF-beta 1 was a delayed transient response because by day 16 the progenitor cell numbers and bone marrow cellularity were identical to the 5FU-treated marrow controls.

Animals↗
PubMed1991

Natural killer (NK) and lymphokine activated killer (LAK) cell activity in patients (PTS) treated with flavone acetic acid (FAA).

Natural killer (NK) cell activity was measured in nine patients with different solid tumors treated with flavone acetic acid (FAA). In three of them, NK cell activity was significantly increased, in two instances even after repeated courses of treatment. A significant increase in lymphokine activated killer (LAK) cell activity was also observed in three of four patients after in vivo treatment with FAA and in vitro incubation of lymphocytes with recombinant Interleukin-2. We observed some inter-individual variability in drug clearance, but no apparent correlation between drug plasma levels (neither peak nor AUC values) and the effects on NK and LAK activity.

Adjuvants, Immunologic↗
PubMed1990

Flavone acetic acid antitumour activity against a mouse pancreatic adenocarcinoma is mediated by natural killer cells.

Flavone acetic acid (FAA) is one of the most active antitumour agents against mouse solid tumours. A number of reports favour the hypothesis that FAA could behave as a biological response modifier; in fact FAA stimulates natural killer (NK) cells, induces secretion of type I interferon and synergizes with interleukin-2 to increase NK/lymphokine-activated killer (LAK) activity in vivo. However, there is no conclusive evidence that the antitumour activity of FAA is mediated via the modulation of NK/LAK cells. The present study was designed to evaluate whether the reported activation of NK cells is instrumental in FAA antitumour activity. FAA (180 mg/kg, i.v. on days 3, 7 and 11 after tumour implant) was significantly effective in inhibiting the subcutaneous growth of the pancreatic adenocarcinoma PAN/03 in C57/Bl mice. After 132 days the number of tumour-free survivors was 36%, whereas in the control group receiving no treatment, or in the group of mice treated with 10 micrograms/mouse of alpha-asialo-GM1 the value was only 0 or 6.7%, respectively. The combination of FAA and alpha-asialo-GM1 resulted in only 6% tumour-free mice. In parallel experiments, splenocytes and peritoneal cells from C57/B1 mice were tested in a standard cytotoxicity NK assay. While animals treated with FAA showed a significant increase in NK activity, those injected with alpha-asialo-GM1 had very low levels, and the combined treatment of FAA and alpha-asialo-GM1 resulted in a lower or similar NK activity compared to that in untreated mice. The fact that the abrogation of the NK-stimulating effect of FAA is accompanied by a lack of anti-tumour activity indicates that, at least in this experimental model, FAA is likely to act via an immunomodulatory mechanism.

Adenocarcinoma↗
PubMed1990

Flavone acetic acid distribution in human malignant tumors.

The pharmacokinetics of flavone acetic acid (FAA) after a dose of 4.8 mg/m2 given i.v. over 1 h was investigated in 13 patients with different solid tumors. The mean volume of distribution and clearance were 52 +/- 4 l/m2 and 2.6 +/- 0.2 l/h x m2, respectively. A tumor or metastasis biopsy was obtained from six patients 2 h after the end of infusion. Tumor FAA levels ranged from 39.6 to 148.8 micrograms/g and were similar to those obtained after a therapeutic i.v. dose of 200 mg/kg FAA in animals bearing Pan/03 tumor, which is very sensitive to the drug. Although FAA tumor concentration could be detected only during one interval and we therefore cannot draw a definitive conclusion, differences in the agent's antitumor activity in mice and patients (i.e. very active in the former and inactive in the latter) are apparently not due to discrepancies in drug distribution and pharmacokinetics.

Adult↗
PubMed1990

Influence of parenteral nutrition on leg nitrogen exchange in injured patients.

Body N balance, 3-methylhistidine (MEH) excretion, amino acid (AA) plasma concentration, and fluxes across the leg were investigated both during fasting and during parenteral nutrition of injured patients in order to better understand protein-sparing mechanisms induced by metabolic support in the whole body and in skeletal muscle. Patients were randomized to receive 15 or 30 kcal/kg.day coupled with 0.30 g of N either with standard or branch-chain (BC)-enriched AA solutions. During fasting, patients were highly catabolic (N balance -14.7 +/- 1.2 g N/m2.day, MEH excretion 422 +/- 25 mumol/m2.day) and showed a high efflux of AA N from the leg (5.08 +/- 2.1 g N/m2.day) without difference between the groups. During treatment, body N balance (-5.55 +/- 0.88, p less than .001) and MEH excretion (284 +/- 20, p less than .001) were significantly reduced without difference among the groups; also, AA N leg efflux (2.64 +/- 0.47, p less than .001) was reduced. Moreover, considering the effect of calorie load, patients receiving 30 kcal/kg.day showed a lower efflux of total AA N and of some AA considered as markers of muscle protein catabolism, such as phe, lys, met, and glu. The main difference between solutions was in the efflux of BCAA; particularly, val and leu efflux was turned into uptake in the BCAA group. No significant difference among the groups was found in N balance and MEH excretion during treatment. In brief, muscle catabolism was reduced in an amount dependent on glucose and insulin load, but it was not influenced by BCAA supply. Whole body net protein catabolism was reduced through different mechanisms, either an increased visceral N retention or a decreased muscle N loss. However, muscle N loss was never abolished even in the high calorie groups.

Adolescent↗
PubMed1990

[New methods and new technics in pedodontics: "conscious sedation"!].

The reasons why is it sometimes necessary to resort in paediatric dentistry to the use of conscious sedation with N2O/O2 are explained together with clinical indications and applications. The excellent results obtained with this technique lead to greater cooperation of the child, to a positive emotional contact with dental treatment and the possibility of performing the necessary therapies with greater precision.

Ambulatory Surgical Procedures↗