Biomedical subjects

G Piatti

Publications and source records attributed to G Piatti.

At least 19 recordsLinked to original sources

PubMed2006

Lung function in beta-thalassemia patients: a longitudinal study.

Patients with beta-thalassemia often present with a restrictive pattern at pulmonary function tests (PFTs) due to several pathogenetic factors. However, the long-term evolution is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, non-smoking patients with beta-thalassemia major and intermedia. We looked for temporal changes in lung function and characteristics that would predict the development of PFT abnormalities. In 1996, 18 patients with major beta-thalassemia (9 males and 9 females; age range: 18-35 years) and 11 patients with intermediate beta-thalassemia (5 males and 6 females; age range: 25-51 years) underwent clinical assessment and PFT, including body plethysmography and gas transfer study (carbon monoxide diffusion capacity, DL(CO)). Patients were reassessed in 2003. An echocardiographic evaluation was also obtained to exclude pulmonary hypertension. In 55.5% of major and 45.4% of intermediate beta-thalassemia patients, a restrictive pattern was found in 1996; in 2003 only 38.8 and 27.2% of patients, respectively, exhibited total lung capacities below the predicted values. DL(CO) was unchanged in both groups of patients, being reduced in 5 thalassemia major patients and within the normal range in intermediate patients. We conclude that asymptomatic patients with beta-thalassemia have a high prevalence of PFT abnormalities, but without significant increases over time. An improvement may be observed when good control of the iron balance is reached with optimal chelation therapy.

Adolescent↗

PubMed2005

Effects of salmeterol on cilia and mucus in COPD and pneumonia patients.

The present study was performed to evaluate the effects of salmeterol xynaphoate on ciliary beat frequency (CBF) of nasal epithelium and on rheological parameters of tracheobronchial mucus. We studied 10 steady-state COPD patients, eight patients with community-acquired pneumonia and eight healthy subjects as controls. They underwent a nasal brushing of the inferior turbinate to study the CBF in basal conditions and following application of salmeterol at 10(-5), 10(-6), 10(-7) and 10(-8) M concentrations directly to the epithelial samples. We also collected sputum samples, in COPD patients only, by the technique for "protected expectoration" for the rheological assessment in basal conditions and following addition of salmeterol at 10(-5), 10(-6), 10(-7) and 10(-8) M concentrations. Only samples with basal viscosity values higher than 2000 mPa/s were admitted. Our results confirmed previous studies that demonstrate a ciliostimulating effect induced by salmeterol. The mean basal CBF was 11.18 +/- 0.75 Hz in control subjects, while the pathological subjects showed a markedly lower basal values: 8.64 +/- 0.88 Hz (p = 0.000) and 8.83 +/- 0.68 Hz (p = 0.000), in COPD and pneumonia patients, respectively. Salmeterol induced ciliostimulation in both patients groups as well as the healthy controls. The maximum increase in CBF, highly significant, was obtained at 10(-6) M concentrations of salmeterol, while this effect decreased at lower concentrations. Regarding the action of salmeterol on rheological parameters, a direct effect of salmeterol on mucus cannot been demonstrated and the described beneficial clinical effects on mucociliary clearance occurring in vivo are probably related to an indirect effect of stimulation of ciliary beat. This preliminary study suggests that, in addition to COPD, salmeterol could be a useful therapeutic agent in pneumonia also, for its positive effect on ciliary movement other than bronchodilation, but this finding needs further investigations.

Albuterol↗

PubMed2004

Nasal ciliary beat after insertion of septo-valvular splints.

OBJECTIVE: At present, endonasal paraseptal splints are devices frequently employed in rhinosurgery. We evaluated the local tolerance of a newly shaped device, the Guastella/Mantovani splint (G/M-SVS), with respect to the physiological mechanism of mucociliary clearance. STUDY DESIGN AND SETTING: The study involved 20 patients who underwent septoplasty and/or turbinoplasty or other nasal surgical procedures. A sample of ciliated cells was obtained by nasal brushing and was examined ex vivo to determine the ciliary beat frequency (CBF) and morphology, before and 15 days after surgery. RESULTS: Before surgery the mean CBF was 10.87 Hz +/- 0.56 Hz and when splints were removed it was 10.25 Hz +/- 1.9 Hz. Morphological evaluation of the ciliary motion after surgery demonstrated a normal, coordinated beat. CONCLUSIONS: The G/M-SVS does not appear to interfere with the physiological mechanism of mucociliary clearance since CBF remain within a normal range. SIGNIFICANCE: This is the first study that demonstrates an optimal tolerability and safety of the septo-valvular splints on nasal mucosa.

Adult↗

PubMed2003

Effects of zafirlukast on bronchial asthma and allergic rhinitis.

Asthma and allergic rhinitis are common conditions, occurring with increasing prevalence and frequently coexist. In both conditions histamine and cysteinil leukotrienes are important pathogenic inflammatory mediators. We evaluated the effects of the leukotriene receptor antagonist zafirlukast, 20mg administered twice daily for 2 weeks, in patients with allergic rhinitis and bronchial asthma during the grass pollen season. Patients underwent skin prick testing, spirometry, rhinomanometry, mucus transport test with saccharine, nasal epithelial brushing to study ciliary beat and, finally, nasal lavage.Thirty-five subjects completed the study. At the end of the study period, zafirlukast significantly reduced asthma and rhinitis symptoms (P< or =0.05); FEV(1) values were unchanged (P=0.10), whereas nasal resistances showed a decrease following treatment (P=0.01). Ciliary beat frequency (CBF) also improved (P=0.00), although mucociliary transport showed no improvement (P=0.87). The number of eosinophils in nasal lavage fluid decreased (P=0.00) while that of neutrophils was unchanged (P=0.09). These positive effects suggest that zafirlukast may be usefully employed in the treatment of both bronchial asthma, as previously demonstrated, and allergic rhinitis.

Adolescent↗

PubMed2001

Nasal ciliary function and ultrastructure in Down syndrome.

OBJECTIVES/HYPOTHESIS: To investigate the in vivo nasal ciliary beat and the ciliary ultrastructure in Down syndrome because, although in this condition an increased susceptibility to respiratory tract infections has been reported by several authors, the nature of this phenomenon is not fully understood. STUDY DESIGN: Experimental study of 18 subjects with Down syndrome and 18 healthy control subjects. METHODS: Ciliary beat frequency (CBF) was measured on samples of ciliated epithelium obtained from the inferior nasal turbinate; a further brushing for ultrastructural analysis was performed only in subjects showing a CBF reduction or a ciliary movement alteration. RESULTS: The mean CBF in the group with Down syndrome was 7 +/- 2.82 Hz, and in the control subjects it was 10.94 +/- 0.65 Hz. In the same 66.6% of subjects with Down syndrome, we observed a fibrillatory movement of cilia and no metachronicity was present. Moreover, in 14 subjects with Down syndrome as hyperproduction of mucus was present. Ultrastructural evaluation at transmission election microscopy instead revealed a normal architecture of cilia. CONCLUSION: We attribute the nature of the mucociliary defect in Down syndrome to recurrent respiratory tract infections causing changes in mucus properties as in rheological parameters and not to a primitive defect of cilia.

Adolescent↗

PubMed2000

Audiological evaluation in adult beta-thalassemia major patients under regular chelation treatment.

With the improved life expectation of beta -thalassemia major patients, new clinical problems, such as hearing damage, must be evaluated. Fifty-seven patients (32 F, 25 M; age range 17-32 years) have been studied to define risk factors for development of sensorineural hearing loss. All patients with beta -thalassemia major received daily chelation therapy with subcutaneous injection of desferrioxamine (30-50 mgkg(-1)per day). We performed an otological visit and pure tone audiometry as well as impedance; patients were followed for 3 years. Four patients with a conductive hearing loss were excluded; 66.6% had a normal audiogram; 22.8% had a slight sensorineural deficit ( </=35 dB HL) with high frequency losses; only two patients (3.5%) had a moderate deficit (between 35 and 75 dB HL). In normal subjects ABR recording gave normal values. There was no association between age, ferritin level, therapeutic index (T.I.) and hearing loss. We conclude that no significant difference exists between beta -thalassemic patients and non-thalassemic subjects of the same age; desferrioxamine treatment seem to be non-ototoxic when employed at the present dosages, but the ototoxicity is probably related to individual susceptibility that is unforeseeable; in any case, the risk of ototoxicity seems to be much less than the benefits which derive from the use of this drug.

Adolescent↗

PubMed2000

Cytokine gene expression and T-cell proliferative responses in lymph node mononuclear cells from children with early stage human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVES: The immunologic events taking place in secondary lymphoid tissue from children with early stage human immunodeficiency virus (HIV) infection are poorly understood. The aim of this study was to investigate cytokine gene expression and proliferative responses in lymph node (LN) biopsies from five children with early stage HIV infection, in the context of LN morphology and viral load. DESIGN AND METHODS: The design of the study was approved by the local Ethical Committee. Cytokine gene expression was studied in LN biopsies and in paired peripheral blood (PB) samples from HIV-infected children by reverse transcriptase-polymerase chain reaction. T-cell proliferation was assessed by 3H-thymidine incorporation. Viral burden in germinal centers was assessed by video densitometric analysis following immunohistochemical staining for HIV p24. RESULTS: Interleukin (IL)-2, IL-4 and IL-5 mRNA were not detected in any LN or PB sample from HIV-infected children. Interferon (IFN)-gamma mRNA was found only in CD8+ cells. IL-12 p35, IL-10, transforming growth factor-(TGF)-beta1, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and IL-16 transcripts were detected in all samples. Proliferation of LN and PB mononuclear cells to polyclonal mitogens and soluble (recall and HIV-related) antigens was impaired as compared with the responses in a group of age-matched healthy controls. INTERPRETATION AND CONCLUSIONS: Changes in cytokine gene expression and T-cell proliferative responses are already detectable in lymph nodes from HIV-infected children at an early stage of disease.

Child↗

PubMed1999

Identification of immunodominant epitopes in the filamentous hemagglutinin of Bordetella pertussis.

The filamentous hemagglutinin (FHA) of Bordetella pertussis is a principal adhesin, which plays a key role in the colonization of the upper respiratory tract. FHA is also a protective antigen, which has been incorporated in the new generation of acellular vaccines against whooping cough. The protein is synthesized as a large 367-kDa precursor, which is then processed into a 220-kDa secreted polypeptide. To optimize the use of this protein for vaccine purposes it would be helpful to define the regions encompassing immunodominant epitopes. Twelve recombinant plasmids have been generated encoding fusion proteins between fragments of the matured-secreted 220-kDa form of FHA and the vector-encoded phage MS2 polymerase. Protein extracts of the resulting recombinant clones have been tested for reactivity with sera from 20 patients convalescent from whooping cough, and two human standard sera. The results indicate the presence of an immunodominant B cell epitope in the polypeptide coded by a 1-kb DNA fragment encompassing positions 5781-6800 of the published sequence. These results suggest that the identified fragment should be conserved in the formulation of vaccines against pertussis.

Adhesins, Bacterial↗

PubMed1999

Beta-thalassemia and pulmonary function.

BACKGROUND AND OBJECTIVE: The survival of patients with beta-thalassemia major and intermedia has improved considerably. This has focused attention on the long-term sequelae of the disease itself and its treatment. The effect of hemosiderosis in major organs (heart, liver, etc) are well-recognized, but the pathophysiology of any lung damage is less clearly understood. We studied lung function changes in 32 patients with beta-thalassemia. DESIGN AND METHODS: Respiratory function tests, CO diffusion and arterial blood gas analysis were performed on 19 patients with beta-thalassemia major (9 F, 10 M) and 13 with beta-thalassemia intermedia (6 M, 7 F). All investigations were performed 24 hours before the patients received a blood transfusion or when they were in a stable state hematologic condition. Echocardiography was performed in all patients and the ejection fraction was employed as a measure of cardiac function. RESULTS: No patient had clinical signs of pulmonary dysfunction. Pulmonary function tests, however, showed a reduction of all main parameters (TLC, FVC, FEV1 and RV) in most patients with beta-thalassemia major, indicating a restrictive type of dysfunction. The pulmonary function of patients with beta-thalassemia intermedia seemed to be preserved. Arterial blood gas values were within the normal range, while in some subjects CO diffusion approached the lower limits of normality. There was no evidence that the observed abnormalities in pulmonary function were secondary to congestive heart failure. INTERPRETATION AND CONCLUSIONS: Iron deposition due to repeated blood transfusions may play a central role in determining lung alterations although the majority of patients are well chelated, suggesting that more than one causal mechanisms could be involved.

Adolescent↗

PubMed1998

The role of chemotherapy in polymorphonuclear phagocytosis in pneumonia.

The efficacy of the host defense system is a determining factor for the outcome of antimicrobial events in infected patients. The neutrophil granulocyte plays a key role in the lung's defense against bacterial invasion and in the absence of a sufficient attraction of functionally intact neutrophils in the lung, following bacterial challenge, severe pulmonary infection may result. The involvement of phagocytes in pneumonia is well known: infiltration of lung parenchyma by neutrophils occurs within a short time in response to infection and is followed by an influx of monocytes. We investigated the effects of antimicrobial therapy in pneumonia on polymorphonuclear neutrophil (PMN) phagocytosis.

Adult↗

PubMed1997

Bacterial adherence in smokers and non-smokers.

Bacterial adherence is thought to be a first important step in the pathogenesis of infection. It is now recognized that bacteria bind to and colonize mucosal surfaces in a highly selective manner via a lock- and key mechanism with complementary receptors on the mucosal surfaces of the host. We studied adherence to buccal cells of a panel of potential respiratory pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa in 18 smokers and 18 healthy non-smokers. Our results show an increased pneumococcal adherence in smokers compared to that of non-smokers and this may explain the role of smoking as a risk factor in the susceptibility to bacterial pneumonia. The other bacterial species tested do not differ in their adhesion values and probably require previous damage of the mucosa before adhesion 1997 The Italian Pharmacological Society.

Bacterial Adhesion↗

PubMed1997

Stable expression of pertussis toxin in Bordetella bronchiseptica under the control of a tightly regulated promoter.

Pertussis toxin (PT) is an essential component of accellular vaccines against whooping cough. However, the industrial production of PT from Bordetella pertussis is impaired by slow growth and poor yields. To overcome these problems, we have constructed a minitransposon containing the tox operon under the control of a tightly regulated promoter responsive to an aromatic inducer. The expression cassettes have been integrated into the chromosome of Bordetella bronchiseptica 5376 and ATCC 10580 bvg. Five recombinant clones containing the tox operon under the control of the Psal promoter, which is activated by the product of nahR, were further characterized. The recombinant clones expressed PT after only 3 h of induction with sodium salicylate at levels similar to those of B. pertussis grown for 24 h. The stability of the engineered phenotype was 100% after 72 h of growth without selective pressure. The growth pattern was not modified either under noninducing conditions or in the presence of the inducer at low concentrations, suggesting that strain performance would not be affected in bioreactors when uncoupled from gene expression. Recombinant PT, which was localized mainly in the periplasm, was purified by affinity chromatography. The recombinant protein was immunologically indistinguishable from wild-type PT and retained its biological activity as determined by the CHO cell-clustering test. These recombinant clones appear to be useful tools for the cost-effective production of PT under conditions of improved biosafety, as demonstrated by the inducible expression of PT uncoupled from the bacterial biomass in a nonvirulent and fast-growing B. bronchiseptica background.

Animals↗

PubMed1996

Human T leukaemia virus type 1 (HTLV-1) specific T-helper cell response: clonal fluctuations and repertoire heterogeneity.

The naive T-helper (Th) repertoire specific for HTLV-1 envelope (env) has been examined on antigen specific T-cell lines and clones from non-immune individuals. Clonal heterogeneity was determined by analysing the T-cell receptor (TCR) Vbeta gene usage and by sequencing the hypervariable regions of the TCR genes. Fluctuations in the V beta gene usage were determined by comparing the TCR Vbeta gene profiles of T-cell lines at different times. We found that a diverse repertoire for HTLV-1 env could be triggered in vitro. Diverse Vbeta genes were used by the same line tested at different times, suggesting that clonal composition of an antigen-specific T-cell line is not constant in vitro. Clones in fact may be up- and down-regulated and clonotypes undetectable at one time point can emerge upon subsequent restimulation. Therefore evaluation of the clonal composition of a T-cell line gives a snapshot of the dominant clones at the time of analysis, and does not tell the whole picture of the antigen-specific ensemble. Furthermore, by sequencing the TCR genes, we identified clones with identical Vbeta gene usage which differed in hypervariable regions (CDR3), indicating their derivation from independent precursors and contributing to overall clonal heterogeneity. If these data can be extended to HTLV-1-infected patients studied in vivo, the Th cell repertoire specific for HTLV-1 env may prove very heterogenous, with important implications for vaccine development.

Base Sequence↗

PubMed1995

Export of Bordetella pertussis serotype 2 and 3 fimbrial subunits by Escherichia coli.

Bordetella pertussis serotype 2 and 3 fimbrial subunits were expressed and exported in Escherichia coli using the recently described expression/secretion vector pCGV1. Two protease deficient E. coli strains (CAG629 and EC538) and two periplasmic-leaky mutants (AE84064 and A593) were transformed with the different constructs and, after thermal induction, proteins present in the various cellular compartments were analyzed by Western blot. The results obtained with the two types of fimbrial subunits were generally the same: a recombinant protein of the expected molecular mass (19.2 kDa) was present in the periplasm of the leaky mutants and of CAG629 strain (Ion protease- and heat shock protease-deficient). Only the expression of the recombinant fimbrial subunits by the tolB A593 mutant resulted in protein release into the extracellular medium. These results indicate that the use of hybrid plasmids based on pCGV1 in combination with the tolB mutant constitute an efficient system for the export of recombinant proteins.

Adhesins, Bacterial↗

PubMed1995

Alterations in surface morphology of Candida albicans produced by rilopirox: a scanning electron microscopy study.

The topological changes produced in Candida albicans cells by incubation in vitro with rilopirox have been investigated by scanning electron microscopy. Rilopirox is a new hydroxypyridone compound with fungicidal activity and the effects of 1x MIC (2.9 micrograms/ml) and 4 x MIC (11.6 micrograms/ml) after 1, 12, 24 hours of incubation were evaluated. The morphological alterations produced by rilopirox are round shapes, collapsed cells, surface folds, clusters, holes and thorn-like extrusion. The effects of rilopirox are already evident at 1 x MIC and after 1 h but their frequency and severity are correlated with the time of incubation and the MIC.

Antifungal Agents↗

PubMed1995

Neltenexine: morphological investigation of protection against elastase-induced emphysema in rats.

The instillation of elastase into airways is a widely adopted experimental method to quickly produce emphysematous lesions that mimic human disease anatomically and physiologically. Experiments were undertaken to determine whether of not neltenexine, a new drug active on surfactant production, would diminish the severity of this disease. Anaesthetized rats were instilled tracheally with porcine pancreatic elastase (46 U/mg) dissolved in saline, in a single instillation of 0.33 mg/100 microliters. Neltenexine was administered in one experiment at the dose of 25 mg/kg i.p. daily for 30 days. In a second test, neltenexine was given at the same dose six days before the elastase instillation and then by the same schedule as in the first experiment; this was done in search of a possible preventive action. At the end of the treatment, lungs were removed and fixed, and slices were dehydrated, critically point dried, coated with gold and observed by scanning electron microscopy (SEM). Rats that were both pretreated and treated with neltenexine showed a significant reduction in the alveolar deformation induced by elastase. There were no differences between pretreated and treated animals. These experimental findings suggest that neltenexine might prove to be useful for preventing pulmonary emphysema. Biochemical studies in man are needed to confirm the clinical application of neltenexine.

Ambroxol↗

PubMed1995

Inhibition of Candida albicans adhesiveness to human buccal and vaginal cells by sub-inhibitory concentrations of rilopirox.

Candida albicans is an opportunistic dimorphic pathogenic yeast which is present on the human mucosal epithelial cell surface. Its adhesion is considered to be an important first step in colonization and in the subsequent symptomatic or asymptomatic infection of buccal or vaginal mucosa. Because the ability to adhere is an important element of the pathogenicity of Candida we investigated in this study the compared effects of sub-inhibitory concentrations (sub-MICs) of rilopirox (CAS 104153-37-9) with those of ciclopirox olamine (CAS 41621-49-2) in inhibiting Candida adhesion to human buccal (BEC) and vaginal cells (VEC). Rilopirox is a new hydroxypyridone antimycotic agent with strong activity, especially against Candida albicans. There was a significant reduction in the mean number of Candida adhering to both buccal and vaginal cells with up to 1/8 MIC rilopirox for buccal and 1/16 MIC for vaginal cells, while for ciclopirox olamine reduction was significant up to 1/16 MIC for buccal and 1/8 MIC for vaginal cells. There were no significant differences in the dose-effect curves for BEC and VEC with either rilopirox and ciclopirox olamine, but on a molar basis, rilopirox was more active than ciclopirox olamine. The present in-vitro results support the developmental concept of an oropharyngeal and vaginal preparation of rilopirox. It can be expected that even sub-inhibitory concentrations of rilopirox exert an important additional effect in the treatment of oral and vaginal candidosis by impairing the pathogenic adhesion process of the fungus.

Antifungal Agents↗

PubMed1994

A novel Escherichia coli expression-export vector containing alkaline phosphatase as an insertional inactivation screening system.

An Escherichia coli expression-export vector was constructed (pCGV1, 6.3 kb) containing the alkaline phosphatase structural gene (phoA) located downstream from the phage lambda pR and pL promoters positioned in tandem and the cIts857 gene encoding lambda thermosensitive repressor. The phoA gene is fused to DNA encoding a hybrid signal sequence that contains the N-terminal portion of the beta-lactamase (Bla) signal sequence and the C-terminal region of the PhoA signal sequence. Within the DNA encoding hybrid signal sequence, a unique NheI restriction site is present where polymerase chain reaction (PCR)-amplified genes may be cloned. The 5' PCR primers reconstitute the C-terminal portion of either the PhoA or Bla signal sequences to restore an intact signal peptide. Recombinant phoA- clones are selected on indicator plates containing 5-bromo-4-chloro-3-indolyl phosphate.

Alkaline Phosphatase↗