Biomedical subjects

S Milano

Publications and source records attributed to S Milano.

At least 55 records · Page 3Linked to original sources

PubMed1994

Chylothorax after blunt chest trauma: an unusual case with a long latent period.

We report on a case of closed chest trauma with an unusual latent period of 11 weeks in a woman 26 years old. The patient had a dual thoracic duct with a dual lesion and was evaluated using lymphography and CT. We discuss the pathogenetic mechanism and the unusual radiological appearance with discontinuity of the duct, and an increase in back pressure which promotes dilatation of lymphatic vessels and nodes. The dual duct had two separate traumatic consequences: a chyloma on the right and leakage in the pleura on the left. Pleuroperitoneal shunting was effective after failure of conservative treatment. Two years after discharge the patient is asymptomatic with normal chest X-ray image. She is near term in a normal pregnancy and without signs of silent malignancy.

Adult↗

PubMed1994

Evaluation of serum levels of soluble CD4, CD8 and beta 2-microglobulin in visceral human leishmaniasis.

The levels of soluble CD4 (sCD4), sCD8 and beta 2-microglobulin (beta 2-M) were measured in sera from patients with visceral leishmaniasis during the course of infection. Levels of sCD4, sCD8 and beta 2-M were raised significantly above levels in normal sera and returned to the normal range after recovery. The decrease in the levels of sCD8 was related to a reduction of anaemia, leukopenia and thrombocytopenia. In contrast, sCD4 levels fluctuated during the period of infection. beta 2-M returned within normal range more rapidly than sCD8 secretion. Our results suggest that T cells are activated during infection, and that it is also possible that the raised levels of these soluble molecules play a role in the impairment of protective immunity.

Adult↗

PubMed1994

The macrophage-activating tetrapeptide tuftsin induces nitric oxide synthesis and stimulates murine macrophages to kill Leishmania parasites in vitro.

The macrophage-activating tetrapeptide tuftsin was able to activate, in a dose-dependent manner, murine macrophages to express nitric oxide (NO) synthase and to produce NO. Tuftsin required lipopolysaccharides for the optimal induction of NO production and synergized with gamma interferon in the induction of NO synthesis. Tuftsin-dependent NO production was sensitive to inhibition by dexamethasone and the NO synthase specific inhibitor LGN-monomethylarginine (L-NMMA). Murine peritoneal macrophages activated by tuftsin were able to kill the amastigotes of the intracellular protozoan parasite Leishmania major in vitro.

Animals↗

PubMed1993

Respiratory interneurons of the lower cervical (C4-C5) cord: membrane potential changes during fictive coughing, vomiting, and swallowing in the decerebrate cat.

The possible roles of interneurons in the C4-C5 cervical spinal cord in conveying central drives to phrenic motoneurons during different behaviour patterns were investigated using intracellular recordings in decerebrate, paralysed, artificially ventilated cats. Eleven cells were tentatively classified as respiratory interneurons since they: (i) could not be antidromically activated from the ipsilateral whole intrathoracic phrenic nerve, and (ii) exhibited large membrane potential changes during eupnea (7.3 mV +/- 3.6, range 2-13.5 mV) or non-respiratory behaviour patterns. Six neurons depolarized in phase with phrenic discharge; four others depolarized during the expiratory phase; one neuron exhibited depolarization during the end of both expiration and inspiration. A variety of responses was observed during fictive coughing, vomiting, and swallowing. The results are consistent with C4-C5 expiratory interneurons conveying inhibition to phrenic motoneurons during different behaviour patterns. The responses of inspiratory and multiphasic neurons suggest that the roles of these interneurons are mode complex than simply relaying central excitatory or inhibitory drive to phrenic motoneurons.

Animals↗

PubMed1993

MICE: a new active combination for non-small cell lung cancer.

We have treated 38 patients with stage III/IV non-small cell lung cancer with the following regimen: mitomycin-C = 6 mg/m2, ifosfamide = 3 g/m2, cisplatin = 75 mg/m2, vindesine = 3 mg/m2 (MICE), intravenously (i.v.) on day 1, every 3 weeks. Among 26 patients with stage IV disease, 15 obtained a partial remission (PR) (response rate = 57%, 95% confidence interval = 38-76), with a median time to disease progression and a median survival of 4.9 and 7.1 months, respectively. 6 out 7 patients with stage IIIA disease were documented as PR and 5 of them underwent radical surgery with two pathologically confirmed complete remissions. Overall toxicity was substantial but manageable: 3 patients had grade III/IV leucopenia (although 5 patients had neutropenic fever) whereas 13 patients experienced grade II/II anaemia. In conclusion we believe that MICE regimen is an interesting combination and warrants further evaluations both for palliation and in a neoadjuvant setting.

Adult↗

PubMed1992

Expression of human IL-1 beta in Salmonella typhimurium. A model system for the delivery of recombinant therapeutic proteins in vivo.

The feasibility of using Salmonella typhimurium aroA mutant (SL3261) to deliver protein therapeutic agents was investigated in a murine model system. We have constructed an Escherichia coli expression plasmid designed to express the human protein IL-1 beta. This plasmid expresses IL-1 beta to high levels (greater than 30% total cell protein) in E. coli. In Salmonella the IL-1 beta is expressed constitutively to about 10% total cell protein, as verified by Western blotting analysis using polyclonal rabbit anti-IL-1 beta antibody. The protein is produced in a soluble and biologically active form. BALB/c mice administered orally or i.v. with S. typhimurium aroA mutants carrying the plasmid produced highly significant antibody responses against human IL-1 beta as determined by a solid-phase RIA. Furthermore, mice injected with the construct were significantly protected against lethal gamma-irradiation (850 rad). This study therefore demonstrates that the vaccine strain of Salmonella mutants can also be used effectively to deliver therapeutic proteins in vivo.

Animals↗

PubMed1992

Active avoidance learning in old rats chronically treated with levocarnitine acetyl.

The aging laboratory animal is recognized as a suitable experimental model for the investigation on drugs potentially able to retard the age-dependent decline in cognitive functions. There is robust evidence that levocarnitine acetyl (ALCAR), the acetyl derivative of carnitine, when administered chronically, prevents some age-related deficits of the central nervous system, mainly at the hippocampal level. On the basis of this evidence and because learning of active avoidance was demonstrated to become impaired with age, we decided to investigate the effect of ALCAR in rats. For statistical evaluation of results, the Cluster Analysis technique was chosen. This procedure pointed out the great heterogeneity of the old population and allowed the classification of the animals into homogeneous groups according to their response pattern. The effect of ALCAR was evident in the higher number of treated old animals yielding escape responses, indicating that ALCAR can preserve, at least partially, learning and memory from the natural decay occurring with age.

Acetylcarnitine↗

PubMed1992

Modulation of IL-2, IFN-gamma, TNF-alpha and IL-4 production in mice of different ages by thymopentin.

The effect of an immunomodulator drug thymopentin (TP5) on the production of various cytokines (IFN-gamma, IL-2, IL-4, TNF-alpha) in mice of different ages has been studied. TP5 enhanced IL-2, TNF-alpha and IFN-gamma production but reduced the IL-4 secretion by splenocytes from aged mice (greater than 120 week old) in vitro. However, it had no effect on the IL-2, IFN-gamma, TNF-alpha or IL-4 production by splenocytes from young and adult mice. TP5 injected subcutaneously was able to induce high levels of IL-2 production by splenocytes from all groups of mice. The TP5 effect on TNF-alpha and IFN-gamma was similar, even though it was significant only in old mice. Furthermore, TP5 was able to significantly reduce IL-4 production in old mice, which normally produced high levels of this cytokine after mitogen stimulation. Since it has been observed in the mouse that the Th1 cells secrete IFN-gamma and IL-2, whereas the Th2 cells preferentially produce IL-3, IL-4 and IL-5, these results indicate that the immunopotentiatory activity of TP5 is due to the preferential up-regulation of Th1 cells.

Age Factors↗

PubMed1992

Multi-phase expiratory inhibition of phrenic motoneurons in the decerebrate cat.

We studied the membrane potential changes of 11 phrenic motoneurons (PMs), located in the C5 portion of the cervical spinal cord, in decerebrate, paralyzed and artificially ventilated cats. Intracellular chloride iontophoresis into PMs could reverse the waves of inhibitory postsynaptic potentials (IPSPs) causing membrane hyperpolarization during expiration. In all PMs, we revealed, in addition to the previously described late expiratory augmenting wave of IPSPs, an early expiratory decrementing wave of IPSPs. Moreover, in three PMs, recorded in two cats exhibiting slow respiratory rhythms, an additional wave of IPSPs was interposed between the early and late ones. The possible origins and roles of these three different waves of inhibition are discussed.

Animals↗

PubMed1992

Discharge patterns of phrenic motoneurons during fictive coughing and vomiting in decerebrate cats.

In decerebrate, paralyzed, and ventilated cats, we recorded the activity of 100 spontaneously active phrenic motor axons during the increased phrenic discharges characteristic of fictive vomiting (FV) and coughing (FC). During control respiratory cycles, approximately one-half the neurons were recruited in the first decile of inspiration; recruitment continued throughout inspiration. During FV, the duration of phrenic discharge was halved; 20 of 26 motoneurons studied were recruited in the first decile of the burst. During FC, recruitment times did not change compared with control, although the duration of the phrenic burst doubled. Discharge frequencies increased and recruitment order of phrenic motoneurons was virtually unaffected during FC and FV. Limited recruitment of previously inactive neurons in the filaments from which we recorded was found during FV and FC. During FV, 1 previously inactive motoneuron was recruited in 16 filaments containing 25 spontaneously active motor axons. During FC, 3 new motoneurons were recruited in addition to the 64 already active in 35 filaments. Recruitment during FV and FC was absent even when recording from filaments known, on the basis of antidromic activation, to contain inactive motor axons. During FV, 10 of 26 motoneurons began their discharges with doublets (interspike interval < 10 ms); doublets occurred in only 4 of 67 motoneurons during FC. Already active phrenic motoneurons contributed to the intense phrenic activity associated with both respiratory (coughing) and nonrespiratory (vomiting) behavior by increases in discharge frequency, earlier recruitment, and doublets; the contribution of previously quiescent motoneurons remains uncertain.

Animals↗

PubMed1992

Membrane potential changes of phrenic motoneurons during fictive vomiting, coughing, and swallowing in the decerebrate cat.

1. The patterns of membrane potential changes of phrenic motoneurons were compared during fictive vomiting, fictive coughing, and fictive swallowing in decerebrate, paralyzed cats. These fictive behaviors were identified by motor nerve discharge patterns similar to those recorded from the muscles of nonparalyzed animals. Phrenic motoneurons (n = 54) were identified by antidromic activation from the thoracic phrenic nerve. Intracellular recordings were obtained from 27 motoneurons during fictive vomiting, 40 during fictive coughing, and 27 during fictive swallowing. Sixteen motoneurons were recorded during both fictive coughing and fictive swallowing, eight during both fictive coughing and fictive vomiting, and two during both fictive vomiting and fictive swallowing. Seven motoneurons were studied during all three behaviors. 2. Fictive vomiting, typically evoked by electrical stimulation of abdominal vagal afferents, was characterized by a series of bursts of coactivation of phrenic and abdominal motor nerves, culminating in an expulsion phase in which abdominal discharge was prolonged both with respect to phrenic discharge and to abdominal discharge during the preceding retching phase. During fictive vomiting, phrenic motoneurons depolarized abruptly, and the amplitude of depolarization was significantly greater than during control inspirations. They then repolarized slowly throughout the phrenic burst, rapidly repolarizing at the end of each phrenic burst during retching and reaching a level similar to that observed during expiration. During the expulsion phase, the pattern was initially the same. However, after the cessation of phrenic discharge, the membrane potential repolarized slowly until the end of the abdominal burst, exhibiting greater synaptic noise than during expiration. One phrenic motoneuron, presumably innervating the periesophageal region of the diaphragm, received a strong hyperpolarization just before the onset of the emetic episode and fired for shorter periods during fictive vomiting than did other phrenic motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Thymopentin reduces the susceptibility of aged mice to cutaneous leishmaniasis by modulating CD4 T-cell subsets.

BALB/c mice are highly susceptible to Leishmania major infection. The susceptibility increases progressively with the age of the mice. Aged mice produce progressively lower levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) but higher levels of IL-4 compared to younger mice. Thymopentin, a pentapeptide with thymopoietin activity, dramatically increases the resistance to Leishmania major infection in aged mice. The thymopentin-treated mice produce enhanced levels of IL-2 and IFN-gamma, but significantly reduced amounts of IL-4. Thus, it appears that the age-related susceptibility to cutaneous leishmaniasis is correlated with the enhancement of Th2 and the reduction of Th1 cell activities. Furthermore, thymic hormone may play an important role in the induction and function of these two subsets of CD4 T cells.

Age Factors↗

PubMed1991

Reduction in the number of UCHL-1+ cells and IL-2 production in the peripheral blood of patients with visceral leishmaniasis.

PBMC from patients with visceral leishmaniasis (VL), before and after successful antimony therapy, were analyzed for their phenotypes and for their ability to produce IL-2 and IFN-gamma and to proliferate against PHA and leishmanial Ag. In agreement with results of earlier studies, PBMC from active VL patients showed a markedly reduced proliferative response and IL-2 and IFN-gamma production, compared with those of healthy controls. The levels of CD4+ and CD8+ T cells were within the normal range, but there was a significant decrease in UCHL-1+ cells (helper-inducer), compared with healthy individuals. The inhibited cellular responses, and lymphokine secretion and decreased level of UCHL-1+ cells in the PBMC of the VL patients returned to the normal range after successful chemotherapy. PBMC from active VL patients were fractionated into adherent cells and nonadherent cells, and the non-adherent were further fractionated into UCHL-1+ and UCHL-1- subpopulations. Results from cell depletion and reconstitution experiments suggest that the IL-2 production by nonadherent cells stimulated with PHA was inhibited by adherent cells, but the IL-2 production by nonadherent cells in response to specific Ag was not. In contrast, UCHL-1- cells seem to mediate the inhibition of Ag-driven IL-2 production by nonadherent cells but not mitogen-stimulated IL-2 secretion by nonadherent cells. Ag-specific IL-2 production principally involves UCHL-1+ cells.

Adult↗

PubMed1991

In vitro release and tissue levels of ileal serotonin after cisplatin-induced emesis in the cat.

We have studied the peripheral mechanisms responsible for the severe vomiting observed in cisplatin treated cats. Release of 5-hydroxytryptamine from isolated portions of the ileum and ileal tissue concentrations of 5-hydroxytryptamine were studied in vitro with control animals and animals previously treated with cisplatin. In the latter, two groups were observed: animals in which cisplatin (single dose, 10 mg/kg) induced vomiting within 4 h and animals that did not vomit within 4 h. Spectrofluorimetric assessment of 5-hydroxytryptamine in the perfusate and ileal tissue revealed that cisplatin increases both release, and tissue levels, of ileal 5-hydroxytryptamine in animals which vomited, whereas only ileal 5-hydroxytryptamine release was increased in animals which did not vomit. This may have clinical implications as cisplatin induced emesis may be more effectively prevented by drugs preventing ileal 5-hydroxytryptamine formation rather than release.

Animals↗

PubMed1991

Effect of isoprinosine on IL-2, IFN-gamma and IL-4 production in vivo and in vitro.

The effects of an immunopotentiating drug, isoprinosine, on the splenocytes of BALB/c mice to produce cytokines were investigated. Isoprinosine enhanced IL-2 production, upregulating the expression of IL-2 receptor in vitro. It also significantly increased the IFN-gamma secretion and decreased the IL-4 production in vivo. The significance of these findings in terms of immune regulation is discussed.

Animals↗

PubMed1991

Diaphragmatic and abdominal muscle activity during coughing in the decerebrate cat.

We studied electrical activity of the phrenic and abdominal nerves and from the diaphragm and abdominal muscles during coughing elicited by stimulation of the superior laryngeal nerves (SLN) in decerebrate spontaneously breathing cats. This activity was compared with that observed after partial and complete paralysis. During coughing, the duration, rate of rise, and amplitude of inspiratory discharge increased concomitantly with activity of the rectus abdominis and external, but not internal, oblique muscle. After end-inspiration, the abdominal muscles discharged with one or more bursts. Similar patterns of activity were observed in phrenic and abdominal nerves during SLN-induced coughing, first in spontaneously breathing and then in paralyzed, ventilated cats. The paralyzed, ventilated decerebrate cat provides a powerful experimental model for studying coughing.

Abdominal Muscles↗

PubMed1991

Protective effect of isoprinosine in genetically susceptible BALB/c mice infected with Leishmania major.

The effects of an immunopotentiating drug Inosine Pranobex (isoprinosine) were investigated in an experimental cutaneous leishmaniasis model. The highly susceptible BALB/c mice treated orally with isoprinosine developed significantly delayed onset of disease when infected with Leishmania major compared to untreated mice. The drug itself is not toxic to the parasite up to millimolar levels in vitro. The increase in resistance to L. major infection is accompanied by a marked decrease in the CD4+/CD8+ ratio and the leishmanial antigen-specific proliferative response of the spleen cells of isoprinosine-treated mice compared to untreated mice. There was a significant increase in the production of IFN-gamma but a decrease in the secretion of IL-3 and IL-4 by the spleen cells of isoprinosine-treated mice in response to concanavalin A with or without L. major infection compared to untreated controls. There was, however, no significant difference in the level of IL-2 production by the spleen cells between mice with or without isoprinosine treatment. These data are consistent with the interpretation that isoprinosine potentiates the resistance to leishmanial infection by up-regulating the host-protective Th1 cells and down-regulating the disease-promoting Th2 cells or, alternatively, by increasing CD8+ T-cell function.

Animals↗

PubMed1990

Rapid quantitative method for measuring phagocytosis of Leishmania promastigotes using a double radiolabelling method.

A double radiolabelling method is described for the measurement of phagocytosis of Leishmania major promastigotes in cultures of murine resident peritoneal macrophages. L. major promastigotes were radiolabelled during exponential growth in RPMI supplemented with [125I]5-iodo-2-deoxyuridine. They were used to infect sodium [51Cr]chromate-labelled macrophages. Phagocytosis was evaluated by measuring the radioactivity of the 125IUdR-labelled parasites detectable inside 51Cr-labelled macrophages by a Beckmann gamma 5500 counting system. This was able to count simultaneously, in two different windows the radioactivity of (a) the parasites and (b) the cells. The technique compares favorably with the conventional light microscopic technique and appears to be more sensitive, totally objective, and easy to use for the rapid analysis of multiple samples. Furthermore, the double radiometric method permits a more precise distinction between adherent and engulfed organisms than does the microscopic assay.

Animals↗