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Biomedical subjects

M La Rosa

Publications and source records attributed to M La Rosa.

At least 19 recordsLinked to original sources
PubMed2004

Interleukin-15, as interferon-gamma, induces the killing of Leishmania infantum in phorbol-myristate-acetate-activated macrophages increasing interleukin-12.

The potential leishmanicidal activity of interleukin-15 (IL-15) was examined while priming with the cytokine phorbol-myristate-acetate (PMA)-activated macrophages and infecting them with Leishmania infantum parasites. The activation of macrophage cultures with IL-15 determined a significant anti-leishmanial activity, comparable with that induced by interferon-gamma (IFN-gamma). The killing of Leishmania in macrophages primed with IL-15, as well as with IFN-gamma, was followed by an increase in the IL-12 synthesis. The neutralization of IL-15 or IFN-gamma, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA-activated macrophages, the neutralization of IL-12 production by a specific anti-IL-12 MoAb reduced leishmanicidal activity induced by IL-15 and IFN-gamma. Data indicate that IL-15 could have a role as an activator of leishmanicidal activity, directly or indirectly, by inducing IL-12 production.

Animals↗
PubMed2004

A nonlinear circuit architecture for magnetoencephalographic signal analysis.

OBJECTIVES: The objective of this paper was to face the complex spatio-temporal dynamics shown by Magnetoencephalography (MEG) data by applying a nonlinear distributed approach for the Blind Sources Separation. The effort was to characterize and differ-entiate the phases of a yogic respiratory exercise used in the treatment of obsessive compulsive disorders. METHODS: The patient performed a precise respiratory protocol, at one breath per minute for 31 minutes, with 10 minutes resting phase before and after. The two steps of classical Independent Component Approach have been performed by using a Cellular Neural Network with two sets of templates. The choice of the couple of suitable templates has been carried out using genetic algorithm optimization techniques. RESULTS: Performing BSS with a nonlinear distributed approach, the outputs of the CNN have been compared to the ICA ones. In all the protocol phases, the main components founded with CNN have similar trends compared with that ones obtained with ICA. Moreover, using this distributed approach, a spatial location has been associated to each component. CONCLUSIONS: To underline the spatio-temporal and the nonlinearly of the neural process a distributed nonlinear architecture has been proposed. This strategy has been designed in order to overcome the hypothesis of linear combination among the sources signals, that is characteristic of the ICA approach, taking advantage of the spatial information.

Algorithms↗
PubMed2004

Cyclosporin is safe and effective in severe atopic dermatitis of childhood. Report of three cases.

Severe atopic dermatitis causes major impairment in the life of both children and their parents. Generally, symptoms can be controlled with emollients, topical steroids, antibiotics, antihistaminic but some patients remain intensely ill and may require treatment with systemic steroids and so on. Cyclosporin has been found to be effective in a variety of inflammatory skin disorders since it reduces the number of activated T-cells expressing interleukin 2 (IL-2) receptors. In order to monitor the safety and clinical efficacy of therapy and days of remission we performed Cyclosporin on 3 children with severe atopic dermatitis, refractory to all traditional therapies. Cyclosporin suspension at dosage of 5 mg/kg daily, in 2 doses for 8 weeks has been used. Cyclosporin blood levels, liver and kidney function, blood pressure and some immunological parameters (eosinophils, IgE, IL-2 receptors) were monitored. All patients showed a marked clinical improvement with reduction of pruritus, erythema, papules, vesciculation, excoriation, scaly crusts and lichenification. No clinical or haematological side effects were demonstrated. The soluble IL-2 receptor concentration decreased even after 8 weeks of treatment in all 3 patients, regardless of IgE levels (case 1: low IgE level; case 2: very high IgE level) as in several others T-cell mediated non IgE-related skin disease. The authors suggest that courses of 8 weeks seem effective and safe as well as longer time in producing early remission with the advantage of a low cumulative exposure to the drug. The main question is whether a prolonged remission will permain as well as continuous therapy. This study underscores the potential value of systemic administration of this powerful immuno-suppressive agent in the treatment of many cases of severe atopic dermatitis working regardless of the IgE values. Although 3 cases report does not justify any definitive conclusion however it does a contribute to understand the heterogeneity of atopic dermatitis and it adds information to its current treatment guidelines.

Child, Preschool↗
PubMed2003

Congenital absence of vas deferens and cystic fibrosis.

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are a relatively frequent cause of male infertility such as congenital absence of vas deferens. This finding suggests that CFTR could play a significant role in the etiopathogenesis of congenital absence of vas deferens. METHODS: To assess how often CFTR mutations and 5-thymidine variant of the polythymidine tract of intron 8 are detected in congenital absence of vas deferens we selected 35 infertile male adults caused by congenital absence of vas deferens. RESULTS: Frequency of mutations differs significantly from that in the general population (2% vs 40% respectively) and the delta F 508 mutation accounts for 35% of these mutations. Abnormal sweat test resulted in several patients with a mutation than in others and this difference was highly significant. CONCLUSIONS: This result confirms the role of CFTR protein in the pathogenesis of this malformation and suggests that CBAVD phenotype can represent a mild form of cystic fibrosis. Consequently genetic analysis should take into account the presence of an associated mutation and patients with bilateral agenesia and their partners should be screened for cystic fibrosis prior to any in vitro fertilization techniques.

Adult↗
PubMed2003

[Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructo-oligosaccharides in children. A multicentric double-blind vs placebo study].

AIM: The aim of this paper is to determine the efficacy of a fructo-oligosaccharides (FOS)-Lactobacillus sporogenes preparation in the prevention of diarrhea due to antibiotics in childhood. METHODS: A multicentre, randomised, double-blind versus placebo study was carried out. A total of 120 children, with active infections requiring antibiotics, were enrolled in the study and treated for 10 days either in the experimental group (F) or in the placebo one (P). The results of the study were recorded from the patients' diary and from follow-up clinical examinations. RESULTS: Out of 98 evaluable patients, 71% in group F had no diarrhea versus 38% in group P. The duration of diarrhea in F and P groups was 0.7 vs 1.6 days (p=0.002), respectively. CONCLUSION: Prophylaxis with Lactobacillus sporogens, associated to FOS, significantly reduced the number of days and duration of events in children with antibiotic-induced diarrhea.

Adolescent↗
PubMed2002

IL-15 in human visceral leishmaniasis caused by Leishmania infantum.

Interleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-gamma (IFN-gamma). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-gamma and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-gamma, one of its indirect effects on Th1 cell activation could be due to the latter's effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.

Adult↗
PubMed2002

Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma.

Interleukin-6 plays a central role in regulating the immune system, hematopoiesis, and acute phase reaction. It interacts with a receptor complex consisting of a specific ligand-binding protein (IL-6R, gp80) and a signal transduction protein (gp130). In this report, serum levels of IL-6 and a soluble form of the interleukin-6 receptor (sIL-6R) were evaluated in patients with hepatocellular carcinoma. The correlation between IL-6 and sIL-6R values, the stage of hepatocellular carcinoma, and main liver function tests was also studied.

Carcinoma, Hepatocellular↗
PubMed2002

Expression of HIP/PAP mRNA in human hepatoma cell lines.

The present study attempts to shed more light on the role of hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) in hepatoma cells. We initially examined, by reverse transcription-polymerase chain reaction (RT-PCR), the HIP/PAP transcripts present in human hepatoma cell lines of different origins and with different grades of differentiation and genetic profiles. We also used DNA sequencing analysis to investigate the structure of the HIP/PAP gene. Further investigation is necessary to define the role of HIP/PAP during the development of human hepatocellular carcinoma and to ascertain whether the use of different transcripts is helpful in regulating HIP/PAP expression in transformed liver cells.

Acute-Phase Proteins↗
PubMed2001

Liver expression in cystic fibrosis could be modulated by genetic factors different from the cystic fibrosis transmembrane regulator genotype.

During a multicentric study conducted in Southern Italy, we studied five sets of cystic fibrosis siblings bearing a strongly discordant liver phenotype, three with genotype DeltaF508/R553X, one with genotype DeltaF508/unknown, and one with genotype unknown/unknown. The siblings of each set were raised in the same family environment, and there were no interpair differences in nutritional state or in therapy compliance. All siblings had pancreatic insufficiency and moderate respiratory expression. One sibling of each of the five sets was free of liver involvement, and the other had severe liver expression. Other causes of liver disease (viral, metabolic, and genetic other than cystic fibrosis) were ruled out. Therefore, environmental factors, nutritional state, and therapy compliance are not involved in the liver expression of cystic fibrosis in the five unrelated sibships. This suggests that modifier genes, inherited independently of the cystic fibrosis transmembrane regulator gene, could modulate the liver expression in cystic fibrosis patients.

Adolescent↗
PubMed2001

Bronchiolitis obliterans organizing pneumonia (BOOP) in a child with mild-to-moderate asthma: evidence of mast cell and eosinophil recruitment in lung specimens.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is rarely described in children and little is known about its pathogenesis. This paper reports on an 11-year-old patient suffering from mild-to-moderate asthma. He presented with a retrocardiac density at chest computed tomography scan that was slow to resolve and failed to respond to antibiotic therapy. Open lung biopsy revealed a histological picture with buds of granulation tissue in respiratory bronchioles and alveolar ducts, with organized extensions into the alveoli. The use of monoclonal antibodies on biopsy specimens demonstrated the presence of an inflammatory process affecting not only the thickened alveolar walls, but also the remaining lung parenchyma, the pulmonary arteries, and the bronchioles. The inflammatory infiltrate consisted mainly of mast cells and eosinophils. The clinical condition improved with steroid therapy. To the best of the authors' knowledge, this is the first report of BOOP in an asthmatic child with recruitment of mast cells and eosinophils documented by using monoclonal antibodies.

Asthma↗
PubMed2001

Double-blind multicenter study on the efficacy and tolerability of cetirizine compared with oxatomide in chronic idiopathic urticaria in preschool children.

BACKGROUND: There are no studies on the use of cetirizine in children under the age of 6. OBJECTIVE: We compared the efficacy and tolerability of cetirizine in patients with idiopathic chronic urticaria to the more widely used antihistamine, oxatomide. METHODS: This double-blind study was performed on 62 patients (38 male and 24 female) with idiopathic chronic urticaria, recruited from four different medical centers of the national territory (Ancona, Cagliari, Catania, and Messina). The children's ages ranged from 2 to 6 years (mean 3.85). The patients were randomly assigned to two treatment groups: one group treated 31 children with cetirizine at a dosage of 5 mg q.d., and a second group treated 31 children for the same amount of time with oxatomide, at a dosage of 25 mg q.d. Sixty-two children began the treatment, but five did not finish the study (three in the cetirizine and two in the oxatomide group). Thus, the clinical study and the statistical evaluation were conducted on 57 children (28 cetirizine and 29 oxatomide). The Student's t test was used to compare severity of the illness and changes in the hematochemical tests. RESULTS: Overall, the effectiveness of the two medications in treating erythema, papules, edema, and itching showed comparable therapeutic activity (P < 0.001). Neither medication produced significant side effects. CONCLUSIONS: The results of the present study suggest that cetirizine may represent an effective and safe pharmacologic therapy for chronic urticaria in preschool children. There was no evidence for changes in hematochemical and urinary values, demonstrating the safety and the tolerability of the two antihistamines, even when given to young children.

Anti-Allergic Agents↗
PubMed2001

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line.

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA accumulation indicates that the inhibiting activity is mainly post-transcriptional. CMTs were unable to modulate TNF-alpha and IL-10 synthesis and they were not effective in modifying the transcription of relative mRNA in J774 macrophages. On the contrary, IL-12 mRNA expression was significantly increased by CMT-1 and CMT-8 with LPS activation. Since IL-12 protein secretion was inhibited by CMTs, these compounds interfere in the blocking of post-transcriptional events. The studies on cell viability showed that various CMTs induced a dose-dependent decrease in J774 macrophage viability. The cytotoxic activity was present even though NO production was inhibited by CMTs. These compounds appear to be able to activate apoptosis in aNO-independent way. Altogether, these results indicate that CMTs can exert anti-inflammatory effects by inhibiting NO synthesis, and they are able to modify cell viability by exerting a strong apoptotic activity.

Acridine Orange↗
PubMed2001

Bronchoalveolar lavage in asthmatic children: evidence of neutrophil activation in mild-to-moderate persistent asthma.

Little information is available on cell profiles and mediator production in the lower airways of children with asthma by comparison with the adult population. To study the bronchoalveolar lavage (BAL) cell profiles and production of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) in childhood bronchial asthma, a retrospective study was performed in 29 children (13 allergic asthmatic children and 16 controls). Six of the asthmatics had mild-to-moderate persistent disease and seven had intermittent asthma. The BAL cell count and ECP and MPO values of asthmatic children were compared with those from 16 controls. The asthmatic patients had higher values than controls for the total cell count (p = 0.08), for neutrophils (p = 0.02), and for ECP and MPO (p < 0.001). MPO levels (p = 0.04), neutrophil count (p = 0.06), and ECP values (p = 0.06) were higher in patients with mild-to-moderate persistent asthma than in those with intermittent asthma. Our results demonstrate that neutrophil-mediated inflammation is greater in patients with more severe asthma.

Adolescent↗
PubMed2001

Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines.

Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti-proliferative and anti-tumour activities. Here, we evaluated in vitro the anti-proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT-1, CMT-3, CMT-5, CMT-6, CMT-7 and CMT-8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT-5, CMT-6, CMT-7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT-3 was endowed with a high anti-proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar to that shown by doxycycline. On the contrary, CMT-1 and CMT-8 were very effective as programmed cell death inducing agents. The apoptotic pathway activated by these compounds involved the activation of caspases, especially caspase-9 and, for CMT-1, also the activation of FAS: Interestingly CMT-8, but not CMT-1, was able to induce apoptosis in multidrug resistant HL60R and in Fas-ligand resistant HUT78B1 cell lines. These properties, together with others previously described (e.g. anti-metastatic and anti-osteolytic activities), suggest that CMT-8 may have important applications in the clinical management of cancer. The comparative analysis of structure-activity relationship of CMT-8 and doxycycline suggests that the C-5 hydroxy moiety may play an important role in conferring activity in multidrug resistant cells. These findings appear to support the hypothesis that CMT-8 may represent an interesting lead for the development of a new class of potent apoptosis inducer agents active in multidrug resistant and Fas-ligand resistant malignancies.

Anti-Bacterial Agents↗
PubMed2001

The acute phase response in Sicilian patients with boutonneuse fever admitted to hospitals in Palermo, 1992-1997.

OBJECTIVES: To study the modifications of some components of the acute phase response (APR) in Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii. METHODS: Sera from 500 Sicilian patients with confirmed BF were studied at the time of diagnosis and every week after treatment, and after recovery for the presence of various inflammatory mediators. Tumour necrosis factor alpha (TNFalpha), interleukin(IL)-6, IL-1alpha, IL-8, soluble TNF receptors (sTNF-R) and sIL-6R were assayed by commercially ELISA kits. C3, C4, factor B, C-reactive protein (CRP), fibrinogen, ceruloplasmin (Cp) and alpha(1)-antitrypsin (AAT) were assayed by a rate nephelometry. RESULTS: Interferon gamma (IFNgamma), IL-6, TNFalpha, and IL-10 cytokines were significantly modified, whereas IL-1 and IL-8 were not detectable in the blood in any phase of infection. sTNF-RI, sTNF-RII and sIL-6 were significantly increased in the first 2 weeks of infection, but sTNF-R levels were not related to the plasma levels of TNFalpha, whereas sIL-6 was directly related to serum IL-6 concentrations. C3, C4, factor B and CRP were significantly increased in the first 2 weeks of infection, but afterwards returned to the normal range, even though CRP was still high in the third week and C3 persisted high after the fourth week. Fibrinogen was high only in the first week in relation to the injury to the endothelial cells (ECs). The anti-inflammatory proteins, Cp and AAT, were extremely high in the first 2 weeks of infection acting as a buffer of APR activation. CONCLUSIONS: These results suggest that R. conorii is able to elicit, after invasion and proliferation in the ECs, the activation of APR. Further work is required to establish if active inhibitory mechanisms are operating during APR, or if there is a spontaneous decay in the initiation events.

Acute-Phase Proteins↗
PubMed2000

Interleukin-12 in human boutonneuse fever caused by Rickettsia conorii.

Interleukin (IL)-12 contributes to the resistance against a number of intracellular pathogens. We examined the potential biological role of IL-12 by studying peripheral blood mononuclear cells (PBMC), its production and its effect on cytokine synthesis in 20 Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii. Data indicate that PBMC from acute BF patients were able to produce IL-12 in response to in vitro stimulation with rickettsial antigen (Ag): this production was higher than that detected in healed patients. Monocytes were the main source of IL-12 by PBMC from BF patients. IL-12 secretion by in vitro Ag-stimulated PBMC from BF patients was potentiated by recombinant interferon gamma (IFN-gamma) or anti-IL-10 monoclonal antibodies (MoAbs). Furthermore, the treatment with anti-IL-12 MoAbs reduced the IFN-gamma synthesis. These results indicate that treatment of PBMC from acute BF patients with IL-12 shifted the response toward a Th1-type cytokine response. Furthermore, IL-12 and IFN-gamma are interdependent and they may be associated with the immunity against rickettsias.

Boutonneuse Fever↗
PubMed1999

Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis.

BACKGROUND: Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper (Allergen immunotherapy: therapeutic vaccines for allergic diseases) "as a viable alternative to parenteral injection therapy to treat allergic diseases" in adults. More controlled studies were required to assess the efficacy and safety of this treatment in children. OBJECTIVE: This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies. METHODS: We used a double-blind placebo-controlled design. Forty-one children with Parietaria -induced rhinoconjunctivitis were randomized to receive sublingual standardized Parietaria judaica extract (n = 20) or placebo (n = 21) for 2 years. The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years. The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients' diary cards. Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters, analyzed after 1 and 2 years of immunotherapy. The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects. RESULTS: A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season (P =.02), with no difference in medication scores. A significant decrease in skin reactivity (P =.002 after 2 years of treatment) and an increase in the threshold dose for conjunctival allergen provocation test (P =.02) were observed in the active treatment group compared with the group receiving placebo. A significant increase in specific IgG(4 ) levels (P =.02) was also observed in the active group. Immunotherapy was well tolerated. CONCLUSION: Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen. The safety profile of this treatment, which constitutes an important issue, indicated good tolerance and compliance.

Administration, Sublingual↗