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Biomedical subjects

D Delfino

Publications and source records attributed to D Delfino.

At least 37 records · Page 2Linked to original sources

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↗

Effect of oral administration of different combinations of killed bacteria on some depressed macrophage functions in tumor-bearing rats.

In the present study, we compared the ability of different bacterial species administered orally in various combinations to restore some depressed peritoneal macrophage functions in tumor-bearing rats. Phagocytosis, killing of Candida albicans and chemotactic response of resident peritoneal cells from treated tumor-bearing rats were influenced by different associations of bacteria. In particular, when Staphylococcus aureus was administered together with other bacterial species, the phagocytic activity of peritoneal cells was restored to normal values, and intracellular killing of C. albicans was enhanced. The results are discussed in relation to the possible influence of mucosal bacterial flora on the level of activation of peritoneal macrophages. The possibility that bacterial species can influence in various ways immunocompetent cells in relation to the different chemical composition of some common structures is also discussed.

Administration, Oral↗

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 effects of cryoapheresis and cytostatic treatment in essential mixed cryoglobulinemia.

We studied the effects of cryoapheresis combined with different immunosuppressive treatments on the course of the glomerulonephritis of essential mixed cryoglobulinemia. The study was carried out on 11 patients. The effects of immunosuppressive treatments on cryoglobulin rebound after cryoapheresis varied widely. In those responding with sustained reduction in serum cryoglobulin levels, creatinine clearance increased, an effect that lasted several years in 4 patients. In one patient cryoglobulin disappeared, with almost fully recovery of renal function and normalization of blood pressure. One patient died of acute liver failure shortly after the first observation and another entered regular dialysis treatment. All the other patients are still alive after follow-up of 2-9 years. These results compare favourably with those reported by other investigators and suggest that cryoapheresis and cytostatic drugs are beneficial for glomerulonephritis associated with essential mixed cryoglobulinemia.

Adult↗

Inhibition of normal rat macrophage functions by soluble tumor products. Effect of systemic treatment with bacterial immunomodulators.

The phagocytic and chemotactic activities of normal rat peritoneal macrophages were inhibited by sera from tumor-bearing rats (TBR) and 3 M KCl extracts of tumor mass. However, sera from Corynebacterium parvum- or Listeria monocytogenes-treated TBR did not inhibit phagocytosis. On the other hand, sera from C. parvum-treated, but not from L. monocytogenes-treated TBR still inhibited the chemotactic response of the normal macrophages. Furthermore, 3 M KCl extracts of tumors from C. parvum-treated TBR did not inhibit phagocytosis and chemotactic response of the same cells. Similar results were obtained with extracts of tumor masses from L. monocytogenes-treated rats. It is suggested that treatment with bacterial immunomodulators can influence the release from neoplastic cells of soluble products influencing normal macrophage functions.

Adjuvants, Immunologic↗

Blood temperature and cardiovascular stability in hemofiltration.

Temperature (T) changes in the blood flowing through the extracorporeal circuit markedly affect cardiovascular tolerance to fluid removal during either hemodialysis (HD) and isolated ultrafiltration. In this study we investigated the effect of blood T changes during postdilutional hemofiltration (HF). To this purpose we compared the changes in mean arterial pressure (MAP) and heart rate (HR) during HF and HD carried out at equivalent T of blood in the venous segment of the extracorporeal circuit. Results show that HF entails some heat loss from blood flowing in the extracorporeal circuit; if heat loss is made similar, HD affords nearly as much blood pressure protection as HF does. On the other hand at equivalent heat gain, HF causes nearly as much hypotension as HD does. We conclude that blood T changes in the extracorporeal circuit affect vascular stability (VS) even in HF. The marginal benefit of HF over HD, still observed at equalized T changes, remains to be elucidated.

Blood↗

[Functional relationships between plasma renin activity and hemodynamic indices in essential arterial hypertension].

Vasoconstriction-volume analysis postulates that arteriolar vasoconstriction is the mechanism of blood pressure elevation in patients with "high-renin" essential hypertension while a volume expanded state with relatively dilated arterioles sustains "low renin" essential hypertension. To test this hypothesis we carried out hemodynamic and PRA studies in 43 essential hypertensives. Cardiac index was directly related to PRA (r=0,41; p less than 0,01), by contrast, peripheral vascular resistances and plasma volume were unrelated to PRA. The data do not support the bipolar hypothesis since vasoconstriction and volume expansion are associated with unpredictable changes in PRA. The direct relationship between CI and PRA may be interpreted as the result of a common factor (presumably sympathetic nervous system) governing both functions.

Adult↗

[Cardiac output and pulmonary blood volume in arterial hypertension of chronic uremia].

To investigate the mechanisms that sustains arterial hypertension in chronic uremia we performed hemodynamic studies in 13 dialysed uremics by means selective radiocardiography (Donato-Giuntini method). The 5 dialysed patients with dialysis controllable hypertension (GROUP B) had higher cardiac indexes (CI) respect to the 8 dialysed normotensive controls (GROUP A) (CI: Group B 4,250 l/min/m2, Group A 3,610 l/min/m2; p less than 0,05). The higher CI in group B appeared independent from the degree of anemia because the two groups had comparable hematocrit values (Hct:Group B 26,2% Group A 26,4%); On the other hand the slight blood volume expansion we observed in group B (7%) respect to group A hardly explains the observed difference in CI. It is interesting that pulmonary blood volume/total blood volume ratio (PBV/TBV) was significantly higher in dialysed hypertensives (PBV/TBV: Group B 14,26%, Group A 11,15%; p less than 0,05) The higher PBV/TBV can be the result of a decrease in venous compliance and could explain the higher CI in group B; further studies however are warranted to elucidate this point.

Adult↗