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Biomedical subjects

G Pesce

Publications and source records attributed to G Pesce.

At least 37 records · Page 2Linked to original sources
PubMed1997

Intercellular adhesion molecule-1 on cultured human epithelial cell lines: influence of proinflammatory cytokines.

The expression of intercellular adhesion molecule-1 (CD54 or ICAM-1) on epithelial cells during acute or chronic inflammation may favor the interaction between epithelial cells and leukocytes expressing the natural ligands of ICAM-1, LFA-1 (CD11a/CD18), and Mac-1 (CD11b/CD18). We have evaluated in vitro the expression of ICAM-1 by a conjunctival (WK) and an intestinal (I407) human continuous epithelial cell line. Cells were cultured for 24 h in the presence or absence of IFN-gamma, TNF-alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, and TGF-beta 1. Both epithelial cell lines showed a constitutive expression of ICAM-1. IFN-gamma at 500 U/ml and TNF-alpha at 200 ng/ml upregulated ICAM-1 expression; IL-1 beta at 100 pg/ml upregulated ICAM-1 on WK cells only. Cells cultured in the presence of both IFN-gamma and TNF-alpha exhibited a mean fluorescence intensity far greater than those cultured with IFN-gamma or TNF-alpha alone. I407 and WK cells were able to release soluble ICAM-1. IFN-gamma and TNF-alpha enhanced the release of sICAM-1. IL-4, IL-6, IL-8, IL-10, and TGF-beta 1 did not affect either ICAM-1 expression or sICAM-1 release. In conclusion, continuously cultured human epithelial cells may express ICAM-1 on their surface and release it in culture medium. These phenomena are upregulated by proinflammatory cytokines.

Cell Adhesion↗
PubMed1997

Molecular events in allergic inflammation: experimental models and possible modulation.

In recent years, a complex molecular network involving cytokines kinins and adhesion molecules has been demonstrated to operate in allergic inflammation. In particular, the adhesion machinery plays a crucial role for the recruitment and locomotion of the inflammatory cells and the Intercellular Adhesion Molecule 1 (ICAM-1) is a hallmark of the allergic inflammatory process. The role and possible modulation of ICAM-1 can be investigated using both eye and nose experimental models. Conjunctival and nasal epithelium are easy to study either under natural allergen exposure or after specific/aspecific provocation tests; furthermore the nasal/conjunctival challenge is well tolerated by the patients. These experimental models have allowed us to investigate in vivo the antiallergic properties of several compounds. Many of the new antihistamines, but also deflazacort and local nasal immunotherapy, were demonstrated capable of reducing both inflammatory infiltration and ICAM-1 expression on epithelia. Because of the central role of adhesion molecules in allergic inflammation, their pharmacological modulation can be regarded as a promising therapeutic approach.

Anti-Inflammatory Agents↗
PubMed1997

Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti-allergic activity.

BACKGROUND: Azelastine is a selective H1-receptor antagonist, which has previously been demonstrated to be effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical and inflammatory events following nasal allergen challenge. Particularly, we focused our attention on ICAM-1 expression on epithelial cells, since it is the natural ligand of LFA-1, an adhesion molecule expressed by leucocytes, including eosinophils. OBJECTIVE: Since azelastine ocular drops are now available, the aim of the present study was the evaluation of the anti-allergic activity in the model of allergen specific conjunctival challenge (ASCC). METHODS: Twenty outpatients with allergic rhinoconjunctivitis due to Parietaria Judaica (Wall Parietary) were included outside the pollen season. The study was designed as randomized, placebo-controlled, double-blind and parallel group, developed in two parts. The former investigated the onset of effect of a single dose of azelastine eye drops administered 20 min after clinical response due to ASCC. The latter evaluated the clinical and inflammatory parameters following ASCC after 7-days treatment with azelastine. Clinical parameters (hyperaemia, itching, lacrimation and eyelid swelling) were evaluated at baseline, 5, 10, 20 and 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. Cytological assessment (number of neutrophils, eosinophils. monocytes and lymphocytes) and ICAM-1 expression on conjunctival epithelial cells were evaluated at baseline, 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. RESULTS: When administered 30 min after ASCC, azelastine produced a clinical effect ranging between 10 and 20 min after eye drops administration (P < 0.01). After 7 days of treatment, 30 min after ASCC, azelastine induced a reduction of symptom scores during EPR and LPR (P < 0.01), a reduction of inflammatory cell infiltration during both EPR (P < 0.01) and LPR (P < 0.01), and a reduction of ICAM-1 expression during EPR and LPR (both P < 0.01). Placebo did not modify any of the studied parameters. CONCLUSION: Azelastine eye drops exert anti-allergic activity, inducing a rapid improvement of clinical events when administered after ASCC, and reducing both symptoms and cellular infiltration when administered before ASCC. Finally, azelastine down-regulates ICAM-1 expression on epithelial conjunctival cells, confirming the results obtained at nasal level.

Adolescent↗
PubMed1997

In situ hybridization analysis of ICAM-1 (CD54) mRNA on conjunctival epithelium during allergic inflammation.

BACKGROUND: The intercellular adhesion molecule ICAM-1 has been detected by immunohistochemical methods on epithelial cells of the conjunctiva and nose during allergic inflammation. OBJECTIVE: The aim of the present study was to evaluate whether ICAM-1 expression on conjunctival epithelium derives from endogenous synthesis or is merely due to passive uptake of soluble ICAM-1 released from inflammatory cells. METHODS: In situ hybridization was performed using a 3' end dygoxygenin-labelled specific DNA oligonucleotide probe on fixed conjunctival smears from allergic subjects challenged with, or naturally exposed to the allergen, and from healthy subjects. Immunocytochemistry for ICAM-1 was performed by alkaline phosphatase antialkaline phosphatase. RESULTS: In allergic patients, both naturally exposed to the allergen and after specific challenge, a clear hybridization pattern on epithelial cells was apparent. Out of allergen exposure, some symptomfree pollinosic subjects, as well as a few healthy volunteers showed mild ICAM-1 mRNA cytoplasmic staining in the absence of immunohistochemically detectable ICAM-1. This finding may explain the very early appearance of ICAM-1 on conjunctival epithelium following specific challenge in allergic individuals. CONCLUSIONS: These results indicate that the presence of ICAM-1 on conjunctival epithelium during allergic inflammation derives from endogenous synthesis and not from uptake of soluble ICAM-1.

3T3 Cells↗
PubMed1996

Resolution of multiple affinity states of 5-hydroxytryptamine-1A receptors labelled by [3H]-8-hydroxy-2-(di-n-propilamino) tetralin in rat hippocampal membranes.

1. We examined the binding of [3H]-8-hydroxy-2-(DI-n-propilamino)tetralin ([3H]-8OH-DPAT) to 5-hydroxytriptamine-1A (5-HT1A) receptors in rat hippocampal membranes. 2. Computer analysis of [3H]-8OH-DPAT displacement curves in the absence and in the presence of 100 microM guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) were best fitted with a three-site model with apparent dissociation constants (Kd) of 0.45, 2.8 and 30 nM; the corresponding binding capacity (Bmax) existing in the three affinity states were 4, 2 and 12 pmol/g of tissue (wet weight), respectively. 3. These results suggest that [3H]-8OH-DPAT binding can be resolved as complex isotherms and we provided evidence that [3H]-8OH-DPAT labels 2 high-affinity GTP gamma S-sensitive and one low-affinity GTP gamma S-sensitive state of 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Low-dose continuous intravenous infusion of 5-fluorouracil for metastatic breast cancer.

BACKGROUND: Third-line chemotherapies for advanced breast cancer are difficult to tailor to the individual patient because of reduced tolerance and significant toxicity. Treatment with a continuous intravenous infusion of low-dose 5-fluorouracil (FU-LDCI) is generally well tolerated and thus, a reasonable option for heavily pretreated patients. PATIENTS AND METHODS: From 1989 to 1995, 106 consecutive patients with advanced breast cancer were treated with FU-LDCI. 5-Fluorouracil was given at an initial daily dose of 250 mg/m2 administered continuously with the aid of an elastomer, non-electronic pump through a permanent central venous line for 21 days followed by a 7-day rest. The median age was 56 years (range, 30-82), the median ECOG Performance Status was 1 (range 0-4) and the median number of metastatic sites was 2 (range 1-4). Sixty-one percent of the patients had previously received more than 2 chemotherapy regimens which in 81% included adriamycin, and in 90% 5-fluorouracil. RESULTS: Eighty patients were evaluable for objective response: 17 of them had partial responses (21%, 95% CI: 14%-31%) and 23 stable disease (29%, 95% CI: 20%-40%). One-hundred five patients were evaluable for subjective response, with 46 reporting improvement (44%, 95% CI: 35%-54%). Previous treatments with either 5-fluorouracil or adriamycin did not predict response to FU-LDCI. Median time to progression for patients with a partial response or stable disease was 259 days (range 82-737). The overall survival for the populations as a whole was 274 days (range 13-2264), and the median dose received was 1904 mg/week (range 753-4329). The main toxic effects were grades I and II mucositis, and nausea and vomiting (observed in 31% and 28%, respectively). Grade III toxicities were uncommon: mucositis in 3%, nausea and vomiting in 3%, anemia, thrombocytopenia and hepatitis in 2%, and skin toxicity (hand-foot syndrome) in 1%. Catheter-related thrombosis was observed in 2% of the patients, and there were no pump failures. A questionnaire concerning the impact of the treatment upon quality of life was completed by all of the 13 patients who were alive at the time of evaluation of the results, and all of them rated FU-LDCI as easy to tolerate. The monthly cost of FU-LDCI (US$1,051.00 in Switzerland) was lower than the cost of weekly low-dose adriamycin (US$1,483.00 in Switzerland), a treatment which is often used as a palliative regimen in similar circumstances. CONCLUSION: FU-LDCI is a useful, cost-effective third-line treatment for patients with metastatic breast cancer who need palliation with cytotoxic drugs.

Adult↗
PubMed1996

Intraepithelial gamma/delta-positive T lymphocytes and intestinal villous atrophy.

We have evaluated the expression of different molecular forms of T cell antigen receptor (TcR) in duodenal biopsies of pediatric patients with different forms of villous atrophy: celiac disease, autoimmune enteropathy, intractable diarrhea of unknown origin, and severe cow milk intolerance. A panel of monoclonal antibodies recognizing alpha/beta and gamma/delta TcR (and gamma/delta TcR subsets) was used for immunostaining. The results showed an increase of T cells with gamma/delta-type TcR in celiac patients and also in patients with other forms of villous atrophy with respect to normal controls. Amongst the gamma/delta TcR-positive cells, the subset expressing the molecular product of V delta 1 region was the most represented. The gamma/delta TcR-positive T cells were mainly located within the epithelium: few of them were observed in the lamina propria. On the basis of these results, we hypothesize that the increased homing of gamma/delta TcR-positive T lymphocytes in gut epithelium observed in celiac disease is, at least in part, related to villous atrophy per se.

Animals↗
PubMed1996

Adhesion molecules in allergy.

Cell adhesion molecules have been recognized to play a major role in a variety of physiological and pathophysiological phenomena, such as embryogenesis, maintenance of tissue architecture and tissue damage repair, recruitment of leukocytes into tissues, immunological reactions requiring cell-to-cell contact. Their role in inflammatory reactions is crucial, in particular their involvement in allergic inflammation has been extensively studied. It has become apparent that the expression patterns and cell localization of certain adhesion molecules are related to the dynamic of allergic inflammation, and specifically to selective migration of eosinophils and interactions with epithelial cells of the target organs. In some instances, cell adhesion molecules by themselves may be regarded as reliable markers for clinical purposes. In addition, the pharmacological modulation of expression and release of adhesion molecules may provide new insight about the mechanisms of action and effectiveness of antiallergic drugs.

Cell Adhesion Molecules↗
PubMed1996

Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro.

BACKGROUND: Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis. OBJECTIVE: We evaluated the possible effects of levocabastine eye drops on early (EPR) and late phase (LPR) inflammatory changes induced by allergen-specific conjunctival challenge (ASCC). We focused our attention on the possible effect of levocabastine on expression of the intracellular adhesion molecule-1 (ICAM-1) on epithelial cells. Such a phenomenon is likely to play an important role in allergic inflammation. METHODS: The study was a double-blind, placebo-controlled, randomized trial, performed in cross-over, outside the pollen season. Ten out-patients suffering from allergic rhinoconjunctivitis due to parietaria judaica (wall parietary) were enrolled. Patients randomly received levocabastine eye drops (0.5 mg/mL) or placebo eyedrops, one drop in the left eye (right eye as control), 30 min before ASCC. Clinical evaluation (hyperaemia, burning-itching, lacrimation and eyelid swelling) and cytological assessment (number of neutrophils, eosinophils and lymphocytes, and ICAM-1 expression on conjunctival epithelium) were evaluated at baseline, 30 min and 6 h after ASCC. In parallel, we evaluated the in vitro effect of levocabastine at concentrations ranging from 2 x 10(-9) M to 2 x 10(-5) M on ICAM-1 expression and shedding by a continuously cultured differentiated epithelial cell line (WK). RESULTS: Levocabastine reduced symptom scores during EPR (15 min and 30 min, P < 0.002), inflammatory cell infiltration during EPR (P < 0.002 for neutrophils, eosinophils and lymphocytes) and ICAM-1 expression on epithelium both during EPR (P < 0.002) and LPR (P < 0.02). LPR symptom scores and inflammatory cell infiltration were only slightly modified by levocabastine treatment. In vitro levocabastine at 2 x 10(-5) M concentration was able to down-regulate basal ICAM-1 expression, although it exerted no effect on ICAM-1 release by epithelium. CONCLUSION: Levocabastine exerts anti-allergic activity, in that it reduces in vivo inflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium. The latter phenomenon may be due, at least in part, to a direct effect of levocabastine on epithelial cells.

Acute-Phase Reaction↗
PubMed1995

Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy.

The natural exposure to house dust mites causes sensitization in genetically susceptible patients. Persistent exposure of sensitized patients causes chronic inflammation, and consequently, hyperreactivity, thus promoting the development of clinical features. Recently, intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells triggered by allergen has been demonstrated and related to the inflammation caused by the allergic reaction. Therefore we evaluated the possible presence of inflammation (i.e., inflammatory cell infiltrate and ICAM-1/CD54 expression on epithelium) at conjunctival and nasal levels in patients with asymptomatic allergic rhinitis caused by mites, in their relatives living in the same environment, and in healthy volunteers. In addition, the possible relationship between inflammation and house dust mite allergen exposure was evaluated. Conjunctival and nasal scrapings of allergic subjects enrolled in the study showed many inflammatory cells. A mild ICAM-1/CD54 expression on conjunctival and nasal epithelium was detectable in allergic subjects, whereas relatives and healthy volunteers showed few inflammatory cells and no ICAM-1/CD54 expression on epithelial cells. A detectable level of house dust mite, sufficient to cause sensitization, was found in all houses. This study demonstrates a minimal persistent inflammation at conjunctival and nasal levels constantly detectable in patients without symptoms who are sensitized to mites and continuously exposed to the natural allergens.

Adolescent↗
PubMed1995

Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early- and late-phase reactions after allergen-specific challenge.

BACKGROUND: Allergen-specific conjunctival challenge (ASCC) is a safe and reproducible experimental model of allergic conjunctivitis and a useful tool in the evaluation of effectiveness and possible mechanisms of action of drugs commonly used in the treatment of allergic diseases. OBJECTIVE: The protective effect of cetirizine on inflammatory changes after ASCC was assessed in 12 patients with rhinoconjunctivitis caused by Parietaria judaica in a double-blind study. METHODS: After a screening ASCC was performed, patients were randomized into two treatment groups; each patient was given cetirizine (oral tablets) 10 mg twice daily, or matching placebo for 3 1/2 days in off-pollen season. Clinical evaluation (itching, hyperemia, lacrimation, and swelling of eyelids) and cytologic assessment (number of inflammatory cells in conjunctival scraping and evaluation of intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells) were performed at baseline, 30 minutes (i.e., early-phase reaction [EPR]), 6 hours, and 24 hours (i.e., late-phase reaction [LPR]) after ASCC, before and after treatment. RESULTS: The EPR clinical events and the EPR total number of inflammatory cells were significantly reduced by cetirizine compared with placebo. The LPR clinical events and inflammatory cell recruitment were reduced by cetirizine in a similar manner. Both eosinophil and neutrophil numbers were decreased by active drug in EPR and LPR. Furthermore, ICAM-1/CD54 expression was significantly reduced by cetirizine in both the EPR and LPR compared with placebo. CONCLUSIONS: This study shows that cetirizine has a protective effect on clinical and cellular EPR and LPR events (including ICAM-1/CD54 expression on epithelium) induced by ASCC.

Adolescent↗
PubMed1994

Effect of streptozotocin-induced diabetes on somatostatin receptors in the anterior pituitary, hypothalamus and cerebral cortex of the male rat.

In order to better understand the mechanisms underlying the reduction in GH secretion in diabetic rats, we have characterized and measured SRIH receptors in the hypothalamus and anterior pituitary gland 5 and 9 days after induction of diabetes in the rat. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats. Chronic insulin replacement therapy partly restored plasma GH and blood glucose levels in these animals. A significant reduction in SRIH receptor concentrations was demonstrated in the hypothalamus and anterior pituitary gland, 5- and 9- days after STZ injection. These changes were not significantly corrected by insulin replacement. Cerebral cortex SRIH receptor concentrations were unaffected by experimental diabetes. We conclude that hypothalamic and pituitary SRIH receptor levels are lowered in diabetic rats. These changes may contribute to aberrant GH secretion in diabetes and they indicate that pituitary sensitivity to exogenous somatostatin should be tested in diabetic patients.

Animals↗
PubMed1994

Effects of conjunctival hyperosmolar challenge in allergic subjects and normal controls.

Nonspecific hyperreactivity to a number of physical, chemical and pharmacological agents in a common characteristics of allergic subjects, which is strictly related to the inflammatory events consequent to an allergic reaction. Hyperosmolar stimulus has previously been shown to cause an inflammatory response inducing mast cell activation and subsequent mediator release. We investigated the clinical and cytological events following conjunctival challenge using a hyperosmolar agent (i.e. glucose solution) in patients with allergy due to pollen, in patients with allergy due to mites and in healthy individuals in order to investigate the possible existence of 'conjunctival hyperreactivity', similar to the well-known nasal and bronchial nonspecific hyperreactivity in allergic patients. Hyperosmolar stimulus was able to produce an immediate inflammatory response evidenced by clinical symptomatology, inflammatory cell infiltrate and CD54 expression on conjunctival epithelium in all allergic subjects and healthy volunteers. House dust mite-sensitive subjects, but not pollen-sensitive subjects studied out of pollen season, showed conjunctival hyperreactivity as shown by histamine challenge, in that they required lower glucose concentrations to elicit the conjunctival reaction. This is probably related to an underlying although mild, inflammation.

Adolescent↗
PubMed1993

Allergic subjects express intercellular adhesion molecule--1 (ICAM-1 or CD54) on epithelial cells of conjunctiva after allergen challenge.

BACKGROUND: Allergic inflammation can be experimentally reproduced in vivo in humans, by means of the conjunctival provocation test with allergen. The allergen stimulation triggers an early clinical response and an almost simultaneous cellular infiltrate. Among the factors that can contribute to the local cellular recruitment, we postulate a possible early involvement of CD54 in the development of inflammation caused by the allergic reaction. METHODS: We used a sensitive immunocytochemical immunoenzymatic alkaline phosphatase-monoclonal antialkaline phosphatase technique to detect the possible expression of CD54 molecule on epithelial cells of conjunctiva in 15 allergic subjects and in 15 healthy individuals in basal conditions and after allergen challenge (Parietaria judaica) during the off-pollen season. RESULTS: At baseline all studied individuals did not evidence CD54 expression on epithelial cells; 30 minutes after allergen challenge, all the allergic individuals showed a marked expression of CD54 on conjunctival epithelium, whereas none of healthy subjects showed any CD54 expression. First, CD54 expression on conjunctival epithelium after specific provocation test appeared as a specific phenomenon occurring only in sensitized subjects; moreover, it is an immediate event concomitant with the local inflammatory infiltrate. Therefore conjunctival epithelium unexpectedly appeared to be more than a bystander in the allergic reaction; it may be perceived as an active participant interacting with the inflammatory infiltrate. CONCLUSIONS: These findings indicate that CD54 may play a central role in the allergic inflammation and strongly support the concept that maneuvers designed to interact with the adhesion machinery expressed on inflammatory cells and epithelium may be a helpful therapeutic approach.

Adult↗
PubMed1992

Effect of diabetes on in vivo and in vitro hypothalamic somatostatin release.

In order to better understand the mechanisms underlying the reduction in growth hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin secretion both in vivo (into hypophysial portal blood) and in vitro (from hypothalamic fragments) 5, 9 and 30 days after induction of diabetes. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9 days after STZ administration. Chronic insulin replacement therapy in diabetic animals partly normalized somatostatin levels as well as plasma GH and glucose levels. A good correlation was observed between in vivo and in vitro experiments. Indeed, somatostatin release from hypothalamic fragments did not change 5 days after STZ-induced diabetes and significantly increased 9 and 30 days after STZ administration. The in vitro increase in hypothalamic somatostatin secretion was observed in 10 as well as in 33 mM glucose concentration in the incubation medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing factor secretion was lowered 5 and 9 days after diabetes induction. We conclude that hypothalamic somatostatin release increases in diabetic rats. These changes may contribute to the reduction in GH secretion in these animals. However, since these changes occur after the onset of plasma GH decrease, a factor(s) other(s) than somatostatin may play a causal role in the reduction in GH secretion.

Animals↗
PubMed1992

[Adrenal cystic lymphangioma. A case report].

Adrenal cysts are uncommon. A case of left adrenal cystic lymphangioma in 16 year old boy is reported. The adrenal cyst was a chance finding during radiological investigation for abdominal pain. Ultrasound and CT scan showed the cyst and suggested the correct diagnosis of cystic lymphangioma of the left adrenal gland. The patient underwent surgery and a left adrenalectomy was performed. Histology confirmed the previous diagnosis of cystic lymphangioma.

Adolescent↗