PubMed HealthSearch

Biomedical subjects

D Delfino

Publications and source records attributed to D Delfino.

12 recordsLinked to original sources

Induction of tumor necrosis factor alpha by Leishmania infantum in murine macrophages from different inbred mice strains.

The present study was undertaken to determine whether the viscerotropic species, Leishmania infantum, endemic in Italy, could induce tumor necrosis factor alpha (TNF alpha) in murine macrophages. Genetically susceptible (Lshs) and resistant (Lshr) mice were used in the attempt to correlate TNF alpha production with the ability to control parasite growth and replication. Resident peritoneal macrophages of C3H/HeN, DBA/2, CBA (Lshr), C57BL/10 and BALB/c (Lshs) mice were infected in vitro with promastigotes at a parasite to cell ratio of 8:1. No significant differences in the percentages of infected peritoneal cells of Lshs versus Lshr mice were observed until 72 h of in vitro culture. On the contrary, Kupffer cells from Lshr mice inhibited Leishmania replication. Peritoneal macrophages of resistant mice produced significantly higher amounts of TNF alpha as compared to susceptible mice. TNF alpha production of both resistant and susceptible mice peaked at about 5 h after the challenge with the parasite. No TNF alpha was found in supernatants of infected Kupffer cells from all the strains tested. The ability of macrophages from susceptible or resistant mice strains to produce TNF alpha after challenge with Leishmania infantum does not seem related to their capacity to control parasite replication in vitro.

Animals

Generation of superoxide anion and candidacidal activity by lipopolysaccharide-treated macrophages from patients affected by neoplasia.

Macrophages, derived from in vitro cultured monocytes from both healthy donors and patients affected by metastatic breast cancer, treated or not with Escherichia coli lipopolysaccharide (LPS), were tested for phagocytosis and intracellular killing of Candida albicans and superoxide anion release. We found a marked impairment in intracellular killing closely linked to the lack of superoxide production in macrophages from patients affected by neoplasia treated or not with LPS. On the other hand, the LPS treatment significantly enhanced the phagocytic activity of all the macrophage populations tested, except for phagocytes obtained from patients affected by neoplasia and differentiated in autologous serum.

Adult

Growth of murine natural killer cells from bone marrow in vitro: role of TNF alpha and IFN gamma.

It has been previously shown that natural killer (NK) cell growth can be induced by interleukin-2 (IL-2) in bone marrow (BM) cultures and that other cytokines (CKs), including IL-1 alpha, act synergistically with IL-2. However, as the effect of IL-2 and IL-1 alpha could be due to direct stimulation of NK progenitor cell growth, as well as to the induction of other factors, we analysed the role of the endogenous production of CKs in BM cultures. Results show that mRNAs specific for tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) are detectable within hours in BM cultures supplemented with IL-2 and IL-1 alpha, and that the amount is higher when both IL-2 and IL-1 alpha are present. Antibodies directed against TNF alpha and IFN gamma abrogate the NK cell development, indicating that these CKs play an essential role. The antibodies, however, had no effect on mature NK cells. Furthermore, pretreatment of BM cells with TNF alpha or IFN gamma before culturing with IL-2, enhances IL-2 responsiveness and NK cell growth. These results suggest that induction of cytokines production may be important for growth of NK cells from BM precursors and that the synergistic effect of IL-1 alpha could be due, at least in part, to increased TNF alpha and IFN gamma production.

Animals

Effect of a new peptidyl-hypoxanthine derivative on natural killer cells and antitumor activity.

A new immunomodifier, [omega-(hypoxanthin-9-yl) pentoxy-carbonyl-leucyl-methionine] (RM06), was synthesized and its effect was evaluated on the activity of Natural Killer (NK) cells. Results indicate that RM06 is able to boost the NK activity of normal mice as well as to augment the regeneration of NK activity of lethally irradiated mice transplanted with syngeneic bone marrow (BM). This later effect also correlated with a significant increase in anti-tumor activity as evaluated by the resistance to metastasis in mice injected with syngeneic melanoma cells. These data indicate that RM06 is able to modulate the NK cell activity as well as the antitumor resistance.

Adjuvants, Immunologic

Blunting of atrial natriuretic factor response to volume expansion by benazepril in hypertensive patients.

To verify the hypothesis that the angiotensin converting enzyme (ACE) level may affect the metabolism of circulating atrial natriuretic factor (ANF), the acute and chronic effects of benazepril on plasma ANF levels were studied in hypertensive patients under basal conditions and in response to acute volume expansion. Ten essential hypertensives entered a double-blind crossover study, and were randomly allocated either to placebo or to 10 mg benazepril orally once a day for 2 days; after a placebo washout period of 2 days the groups were crossed over. On the second day of each crossover period, volume expansion was induced by infusing 1 litre saline in 30 min, and blood samples for ANF measurements were drawn at times -5, 0, 5, 15, 30, 35, 40, 50 and 60 min. Oral benazepril at 10 mg/day was then given to all patients for 4 weeks, and the volume expansion with saline was repeated. After the 2-day acute benazepril treatment, blood pressure fell from 166.1 +/- 3.6/105.1 +/- 0.9 to 140.1 +/- 4.6/85.6 +/- 2.1 mmHg (P less than 0.01 for both systolic and diastolic blood pressure), whereas ANF fell from 29.4 +/- 3.6 to 24.1 +/- 3.7 pg/ml (NS) after the acute benazepril treatment and to 17.7 +/- 3.6 pg/ml (P less than 0.01) after the chronic benazepril treatment. The volume expansion itself did not induce significant changes in mean arterial pressure, either during the placebo treatment or during the acute chronic benazepril treatment. The rise in ANF values in response to saline infusion during placebo was prompt, beginning at min 15 and reaching a maximum at min 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Modulation of macrophage functions by corynebacterium parvum preparations.

Corynebacterium parvum has been used as an anti-tumor agent in both animal experiments and clinical trials; nevertheless it is not well established the mechanism of action, since both T-dependent and T-independent ways of action have been proposed. On the other hand, mononuclear phagocytic system activation cannot be ruled out in the immunomodulation carried out by C. parvum. In the attempt to better understand the effects of C. parvum on macrophage functions, experiments were carried out on tumor-bearing rats with a decline of peritoneal macrophage activities as a result of the tumor development. For this purpose three different preparations of C. parvum were investigated: a) the first preparation was obtained by heat-inactivation of bacteria at 60 degrees C for 1h; b) the second by formalin-treatment of bacteria; c) the third obtained from Burrough Wellcome as a formaline-killed suspension in 0.01% w/v thiomersal saline. Each preparation was used at 7 mg/ml dry weight and administered subcutaneously, three days after tumor grafting. The results showed that all three preparations were capable to hinder the tumor mass growth. Macrophage functions as phagocytosis, intracellular killing, intrinsic and extrinsic anti-Herpes Simplex Virus activities, were restored to normal values by each of the preparations used. Nevertheless, concerning the chemotactic activity a discrepancy was noted among the three preparations, since the heat-inactivated one was able to carried out a complete restoration.

Adjuvants, Immunologic

Double-blind randomized, crossover trial of calcium supplementation in essential hypertension.

In a double-blind, randomized, placebo-controlled, crossover trial, 23 middle-aged patients with mild to moderate essential hypertension were given an oral calcium supplement (1 g/day) for 8 weeks. At the end of this period, eight patients continued with this treatment for an additional 2 weeks but were also given 0.5 micrograms/day of 1,25-(OH)2 vitamin D3. In the 21 patients who completed the study, arterial pressure during the calcium-supplemented phase was almost identical to that of the placebo phase. In eight patients, mean arterial pressure (MAP) had changed by greater than 5 mmHg at the end of the calcium-supplemented period, compared with the end of the placebo phase (six patients showed an increase in MAP and two a decrease). Changes in arterial pressure were unrelated to age, plasma ionized calcium, parathyroid hormone (PTH), plasma renin activity (PRA), plasma aldosterone, 24-h urinary calcium, sodium and potassium and were only weakly related to body weight. In the eight patients who continued with the treatment of calcium plus 1,25-(OH)2 vitamin D3 after the 8-week study period, arterial pressure changed very little and not significantly. These results do not support the suggestion that calcium supplements lower arterial pressure in middle-aged subjects with mild to moderate essential hypertension.

Adult

Effect of ultrafiltration on plasma concentrations of atrial natriuretic peptide in haemodialysis patients.

We have investigated the influence of body fluid volume status on plasma levels of immunoreactive atrial natriuretic peptide (irANP) in eight uraemic patients on chronic haemodialysis, including two diabetics with severely impaired reflex control of the heart. IrANP was significantly higher in volume-expanded uraemic patients (36 +/- 16 pg/ml) than in a group of seven age and sex-matched normal subjects (14 +/- 2 pg/ml), and fell consistently, approaching the normal range after the removal of 2.0-4.3 litres of isotonic plasma ultrafiltrate (by isolated ultrafiltration). Plasma levels of the hormone were strictly related to right atrial pressure. The irANP response to ultrafiltration in the two diabetics was similar to that of the other uraemic patients. The results suggest that the elevated irANP levels found in volume-expanded uraemic patients depend largely on fluid overload per se. The preserved irANP response to ultrafiltration of the two diabetics with severe autonomic neuropathy indicates that in chronic renal failure irANP secretion may be regulated independently from autonomic influences.

Adult

The restoration of impaired macrophage functions using as immunomodulator the Corynebacterium granulosum-derived P40 fraction.

Many microorganisms and compounds of microbial origin exhibit immunomodulatory activities and have been extensively used in immunotherapy of experimental animal tumors and in patients with neoplasia. In this paper we describe the effect of the C. granulosum-derived P40 fraction on the growth and metastatization of the transplantable epithelioma T8 of Guèrin. Moreover, we evaluated the effect of P40 treatment on several depressed macrophage functions of tumor-bearing rats. In particular, the phagocytic and chemotactic activities of such cells were studied, as well as the antiviral intrinsic and extrinsic activities against HSV-1 and the anti-Toxoplasma gondii activity. All these functions were depressed in untreated tumor-bearing rats. Administration of a single intravenous injection of P40 fraction led to the restoration of all depressed macrophage activities to normal values. In particular, the possibility of restoring the antimicrobial activity of macrophages from tumor-bearing rats by treatment with this immunomodulator is of great concern when one considers the increasing incidence of opportunistic infections in immunocompromised hosts. Results are discussed in terms of both the possible mechanism of action of P40 and of its possible target cells.

Adjuvants, Immunologic

Effects of a new quinoline derivative, ciprofloxacin, on some professional phagocytic cell functions.

This study reports the effects of ciprofloxacin on in vitro chemotactic, phagocytic and bactericidal activity of human polymorphonuclear leukocytes, human mononuclear cells differentiated in vitro and rat peritoneal macrophages. After in vitro preincubation with different concentrations of ciprofloxacin, acridine orange vital staining for phagocytosis and killing and the Boyden chamber for chemotaxis evaluation were used. Results obtained with different cell types showed no negative effects on the different functions tested, even at concentrations ranging from about 100 micrograms/ml.

Animals

Long-term cultures of mouse bone marrow cells: a model for studying the generation of natural killer cells.

We investigated the generation of natural killer (NK) cells, using a long-term bone marrow culture (LTBMC) system. Mouse bone marrow cells were cultured for 2 weeks in complete medium without growth factors to obtain an enriched population of NK precursor cells. When these cells were recultured in the presence of interleukin-2 (IL-2) and conditioned medium (CM) from LTBMC, lytic NK cells were generated within 4 days. Replacing CM with fresh medium, before adding IL-2, decreased NK cell generation markedly, suggesting that endogenous factors present in CM were necessary for IL-2 induction of NK cells. NK cell precursors were also cultured with a combination of IL-2 and interferon-gamma (IFN-gamma) or IL-2 and tumor necrosis factor-alpha (TNF-alpha), but no CM. Results show that IFN-gamma and TNF-alpha were able to substitute CM. The addition of anti-IFN-gamma or anti-TNF-alpha antibodies to LTBMC cells, cultured in the presence of IL-2 and CM, inhibited cytotoxicity induction in a dose-dependent manner. The data indicate that IFN-gamma and TNF-alpha production may be required for IL-2 induction of NK activity, and are consistent with the hypothesis that NK generation involves collaboration between IL-2 and other bone marrow microenvironmental growth factors.

Animals