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Biomedical subjects

G Nicoletti

Publications and source records attributed to G Nicoletti.

At least 19 recordsLinked to original sources

Chronic peripheral arteriopathy is associated with seropositivity to Chlamydia pneumoniae.

The study was carried out to clarify the correlation between Chlamydia pneumoniae infection and peripheral arterial disease (PAD). The level of specific antibodies of the 133 consecutive patients suffering from PAD at 2nd stage of Leriche's classification were compared with 60 healthy controls by using a commercial Micro-IF Test. A higher incidence of serological evidence of C. pneumoniae infection was found in the patients (106/133) than in controls (6/60). These results are in agreement with other findings that measured the infection in atheromasic plaques. A strong cause-effect relationship between bacterial infection and peripheral arterial disease was not found, but the raised seropositivity level could be considered as a target for medical therapy of PAD.

Antibodies, Bacterial↗

The Sentinel Project: an update on the prevalence of antimicrobial resistance in community-acquired respiratory Streptococcus pneumoniae and Haemophilus spp. in Italy.

A total of 460 Streptococcus pneumoniae and Haemophilus spp. collected from respiratory infections during 2000 was tested for their susceptibility to 15 selected antibiotics. Overall, penicillin resistance among pneumococci was 10.5%, while lack of susceptibility to macrolides, co-trimoxazole, tetracycline and chloramphenicol reached 35.2%, 26.2%, 22.6% and 6.0%, respectively. Amoxicillin/clavulanic acid and levofloxacin were the most potent compounds (100% and 99.9% susceptible strains, respectively). Among isolates of Haemophilus influenzae and Haemophilus parainfluenzae, beta-lactamase production (12.5% and 10%, respectively), and co-trimoxazole (19.9% and 40.0%) and clarithromycin (11.2% and 40.0%) resistance were the prevalent threats. This study confirms the trend observed in Italy since 1992: macrolide resistance among respiratory microorganisms is increasing, while several drugs including amoxicillin/clavulanic acid, third generation injectable cephalosporins and fluoroquinolones remain active on the great majority of these pathogens.

Community-Acquired Infections↗

Antibiotic susceptibility and serotype distribution in Streptococcus pneumoniae circulating in Italy: results of the SEMPRE surveillance study (2000-2002).

During 2000-2002, 20 clinical microbiology centres collected 1623 Streptococcus pneumoniae isolates. Susceptibility to penicillin, amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime, cefotaxime, clarithromycin, ciprofloxacin, levofloxacin, rifampicin and teicoplanin was determined locally by the Etest and/or by the microdilution method by three co-ordinating centres. Total resistance to penicillin increased from 15.2% to 16.1% and macrolide resistance increased from 37.9% to 43.7%. Overall, the most effective drugs (>99% susceptible strains) were amoxicillin, amoxicillin/clavulanic acid, levofloxacin and rifampicin. The most frequent serotypes were: 23F (15.8%), 3 (10.8%) 14 (9.1%), 19F (9.1%), 6B (7.2%), 19A (6.9%) and 6A (4.8%). In conclusion, penicillin and macrolide resistance is increasing in Italy, whilst fluoroquinolone currently remains active. The most common serotypes circulating are included in the heptavalent conjugate vaccine, with the exception of type 3.

Anti-Bacterial Agents↗

Is dermolipectomy effective in improving insulin action and lowering inflammatory markers in obese women?

OBJECTIVE: Obesity is a major risk factor for coronary heart disease, and surgical treatment of obese patients as part of a multidisciplinary approach seems to provide faster results than diet therapy. The aim of this study was to evaluate the effect of dermolipectomy on insulin action and inflammatory markers in 20 obese women. PATIENTS: At baseline and 40 days after dermolipectomy, 20 obese women underwent indirect calorimetry and hyperinsulinaemic glucose clamp. Twenty obese nonsmoking females (age range 25--40 years) volunteered for the study. All subjects had a stable body weight for 2 months before the study. No patient was affected by cardiovascular and/or pulmonary disease, type 2 diabetes, thyroid dysfunction, acute or chronic hepatitis, renal insufficiency or cancer. No patients was receiving any drug therapy and all measurements were made during the follicular phase of the menstrual cycle. RESULTS: At baseline, fat mass (FM) correlated with plasma triglycerides (r=.58, P<0.009), free fatty acids (FFA) (r=0.73, P<0.001), insulin (r=0.70, P<0.002), leptin (r=0.55, P<0.01), adiponectin (r=-0.32, P<0.02) and resistin (r=0.31, P<0.01), insulin sensitivity (IS) (r=-0.59, P<0.005) and respiratory quotient (Rq) (r=0.62, P<0.002). With regard to inflammatory markers, FM was significantly correlated with plasma interleukin (IL)-6 (r=0.71, P<0.001), IL-10 (r=-0.67, P<0.002), tumour necrosis factor-alpha (TNF-alpha) (r=0.78, P<0.001) and soluble IL-6 receptor (sIL-6r) (r=-0.65, P<0.003). Dermolipectomy resulted in a significant decline in total FM of 2.3+/- 0.2 kg. A significant decline in BMI was also observed (30.0+/- 0.08 vs. 31.1+/- 0.7 kg/m(2)). After 40 days a significant decline in plasma resistin (P<0.001) and inflammatory markers and an increase in plasma adiponectin (P<0.03) were observed. Those metabolic changes were accompanied by a significant improvement in insulin-mediated glucose uptake (P<0.001), substrate oxidation and degree of inflammation. Changes in FM following dermolipectomy correlated with the changes in IS (P<0.01), substrate oxidation and FFA (P<0.001). CONCLUSIONS: In obese patients, dermolipectomy is associated with weight lost, improved glucose handling and lower inflammatory markers.

Adiponectin↗

Antimicrobial susceptibility patterns of contemporary pathogens from uncomplicated urinary tract infections isolated in a multicenter Italian survey: possible impact on guidelines.

During 2004 four Italian Laboratories assessed the prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female out-patients. A total of 600 urine samples from individuals aged 18-65 were studied. The overall prevalence of Escherichia coli was 85.3%. Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis, Enterococcus faecalis and other rarer species were far less represented. Determination of the antibiotic susceptibility pattern of the entire collection of E. coli (512 organisms) revealed that among the drugs analyzed ampicillin was the least active molecule with only 62.5% of the strains being inhibited. Amoxicillin-clavulanate and cefuroxime displayed a higher potency (87.7% and 89.2% respectively). Cotrimoxazole inhibited only 70.1% of the uropathogens. The three fluoquinolones tested had comparable activity ranging from 83.0% for ciprofloxacin, to 83.6% for levofloxacin and 84.9% for prulifloxacin, indicating an identical spectrum of cross resistance. Nitrofurantoin (96.7%) and fosfomycin (98.6%) were the most potent drugs. Against the whole collection of uropathogens, only cefuroxime, nitrofurantoin and fosfomycin overcame the threshold of 90% activity, with the fluoroquinolones and amoxicillin-clavulanate suffering from about 15% resistance. The results of this survey strongly support the conclusions of recent Italian guidelines concerning the best empiric treatment of UTI in this country today.

Adolescent↗

Activity of telithromycin against multi-drug resistant Streptococcus pneumoniae and molecular characterization of macrolide and tetracycline resistance determinants.

The antistreptococcal activity of telithromycin and 11 different comparators was evaluated in 26 multi-drug resistant (MDR) Streptococcus pneumoniae strains collected during 2002-2003 as part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) Italian Surveillance Program. The strains were characterized for their susceptibility to antibiotics both at the phenotypic and genotypic levels; furthermore, the association of erm(B), mef(A) class and tet(M) genes, as well as the mobile elements carrying them were determined. The strains in this study were resistant to penicillin (MIC > or = 2 mg/l) in 23.1% of cases, resistant to tetracycline in 88.4%, to cotrimoxazole in 34.6% and cefuroxime in 26.9% while only telithromycin and levofloxacin retained 100% activity against all microorganisms. Co-existence of different resistance determinants was found in 19.2% of all isolates collected in our laboratory, coming from southern Italy. Twenty-three isolates showing the MLSB phenotype of resistance possessing the erm(B) gene (88.5%), associated with tet(M), were carried on the same Tn1545-like element, while two isolates showing the M phenotype possessing the mef(A) gene alone, were carried on Tn1207.1. In only one strain were mef(E) and tet(M) together carried on Tn2009.

Anti-Bacterial Agents↗

New target antigens for cancer immunoprevention.

Prevention of cancer through the activation of the immune system has been explored in recent years in preclinical systems thanks to the availability of several new transgenic mouse models that closely mimic the natural history of human tumors. The most thoroughly investigated model of cancer immunoprevention is the mammary carcinoma of HER-2/neu transgenic mouse. In this system it has clearly been shown that the activation of immune defences in healthy individuals can effectively prevent the subsequent onset of highly aggressive mammary carcinomas. A complete prevention was obtained using a combination of three signals (the so called "triplex" vaccine) that included the specific antigen (p185, the product of HER-2/neu) and nonspecific signals like allogeneic histocompatibility antigens and interleukin 12. The analysis of protective immune responses in models of cancer immunoprevention revealed some unexpected features, in particular the central role of antibodies in immunoprevention, at variance with conventional immuno-therapy which is firmly based on cytotoxic T cells. In the HER-2/neu system anti-p185 antibodies, in addition to immunological functions leading to tumor cell lysis, inhibit p185 dimerization and induce its internalization, resulting in the inhibition of mitogenic signaling. Most current tumor antigens appear to be unsuitable targets for cancer immunoprevention. An ideal antigen should have a crucial pathogenetic role in tumor growth to avoid the selection of antigen loss variants. Downregulation of major histocompatibility complex (MHC) expression during tumor progression frequently limits antigen recognition by MHC-restricted T cells. Thus an ideal antigen for cancer immunoprevention should be recognized both by T cells and by antibodies. Antibody binding to cell surface oncogenic determinants, in addition to complement- and cell-mediated tumor cell lysis, can block mitogenic signaling and induce internalization, resulting in tumor growth arrest. A search for new tumor antigens should be conducted among molecules that are directly involved in neoplastic transformation and are recognizable by the immune response also in MHC loss variants. Novel tumor antigens fulfilling both conditions will be crucial for the development of cancer immunoprevention and will provide new targets also for cancer immunotherapy.

Animals↗

Effect of liposuction on insulin resistance and vascular inflammatory markers in obese women.

Liposuction is one of the more common elective surgical procedures in the US and is supposed to be on the increase. There are no reported studies specifically addressing the metabolic sequelae of liposuction in obesity. The aim of the present study was to investigate the role of large-volume liposuction on insulin resistance and circulating inflammatory markers in obese people. Thirty healthy premenopausal obese (body mass index (BMI) from 30 to 45) and 30 age-matched normal weight (BMI<25) women were studied. In obese women, insulin sensitivity, as measured by the Homeostasis Model Assessment (HOMA=fasting plasma glucose x fasting serum insulin divided by 25), as well as serum adiponectin, the novel adipocytokine with insulin sensitising properties, were significantly lower, as compared with nonobese women (p<0.01), indicating insulin resistance; on the contrary, serum concentrations of the proinflammatory cytokines IL-6, IL-18 and TNF-alpha, as well as the sensitive marker of inflammation C-reactive protein, were significantly higher (p<0.01). All obese women were submitted to a single large volume liposuction (superwet technique): the mean aspirate volume was 3540 ml (range 2550-4670), corresponding to a net lipid loss of 2.7+/-0.7 kg (mean+/-SD). After six months of stable body weight after liposuction, women were less insulin resistant (p<0.05), had reduced concentrations of IL-6, IL-18, TNF-alpha and CRP (p<0.05-0.02), and increased serum levels of adiponectin (p<0.02) and HDL-cholesterol (p<0.05). There was a significant correlation between the amount of fat aspirate and changes in HOMA (r=0.28, p<0.05), TNF-alpha (r=0.31, p<0.02), and adiponectin (r=-0.34, p<0.02), as well as between the decrease in TNF-alpha and the increase in adiponectin after the surgical procedure (r=-0.45, p<0.01). Our study demonstrates that liposuction is safe and free of metabolic sequelae in obese women, pending a careful screening of the patient. Moreover, it is associated with amelioration of insulin resistance and reduced circulating markers of vascular inflammation which may help obese subjects to reduce their cardiovascular risk.

Adult↗

Antimicrobial susceptibility profiles of Pseudomonas aeruginosa and Staphylococcus aureus isolated in Italy from patients with hospital-acquired infections.

Here we report the results of the Sentinel Project 2000 and give the susceptibility to selected antibiotics of 108 Pseudomonas aeruginosa and 108 Staphylococcus aureus strains isolated from patients with hospital-acquired lower respiratory tract infections. In P. aeruginosa, susceptibility to aztreonam and ciprofloxacin was lower than 50%. The resistance rate to beta-lactams was up to 25% and to amikacin 15.7%. Blood isolates showed 80-90% susceptibility to all antibiotics tested except for aztreonam and tobramycin. Overall, oxacillin resistance in S. aureus was 45%, reaching 64.3% among the bronchoalveolar lavage isolates, and 42.9% among the blood isolates. These worrying results confirm the need for continuous monitoring of bacterial resistance trends in the hospitals, mainly in ICUs.

Anti-Bacterial Agents↗

Presence of the ica operon in clinical isolates of Staphylococcus epidermidis and its role in biofilm production.

Staphylococcus epidermidis is an important cause of catheter-associated infections, which are attributed to its ability to form a multilayered biofilm on polymeric surfaces. This ability depends, in part, on the activity of the icaADBC locus and the icaR gene, which are involved in the production of the polysaccharide intercellular adhesin (PIA) that is functionally necessary for cell-to-cell adhesion and biofilm accumulation. The present study determined: (1) the prevalence of the icaADBC operon in S. epidermidis isolates from catheter-related and other nosocomial infections; (2) the correlation between the presence of this operon, biofilm production and resistance to antibiotics; (3) the expression of ica genes and biofilm production; and (4) the genetic relatedness of the isolates. The results showed that icaRADBC was present in 45% of the isolates included in the study, and that such isolates were significantly more resistant to the main antibiotics tested than were ica-negative isolates. The presence of the entire cluster did not always correlate with biofilm production, determined under different culture conditions, but there was evidence to suggest a correlation when at least two genes (icaAD) were co-transcribed. Eight of 18 ica-positive isolates had the entire operon in the same restriction fragment after pulsed-field gel electrophoresis, but the isolates were not clonal. Estimation of genetic relatedness indicated that ica-positive S. epidermidis isolates belonged to different lineages, distributed in only one of two major clusters, with a genetic distance of c. 0.12.

Bacterial Adhesion↗

NACP-REP1 polymorphism is not involved in Parkinson's disease: a case-control study in a population sample from southern Italy.

Contradictory evidence has been reported on the role of the polymorphic mixed dinucleotide repeat (NACP-REP1) of the alpha-synuclein gene as a risk factor for sporadic Parkinson's disease (PD). In the present study we genotyped the NACP-REP1 polymorphism in 189 PD patients from southern Italy and 182 healthy control subjects. We failed to demonstrate an association of any NACP-REP1 allele with PD.

Aged↗

Internalization-associated proteins among Streptococcus pyogenes isolated from asymptomatic carriers and children with pharyngitis.

Sixty-two strains of Streptococcus pyogenes isolated from 30 asymptomatic school children and 32 children with pharyngitis were characterized to analyze the involvement of 2 fibronectin-binding proteins (F/SfbI and PrtF2/PfbpI) in S. pyogenes colonizing asymptomatic carriers and to determine the possible association between these proteins and the genes associated with macrolide resistance. In this study, we demonstrated that the proportion of S. pyogenes strains carrying the pfbpI gene was significantly higher among asymptomatic carriers (80%) than among children with pharyngitis (53%; P<.05). With regard to the proportion of prtF1-positive strains, no significant differences were found between the 2 groups (70% vs. 69%, for asymptomatic carriers and children with pharyngitis, respectively). Another important finding is the significant association between macrolide resistance and protein F/SfbI (P<.001) in both groups. These results suggest that the presence of the pfbpI gene can be linked to the ability of S. pyogenes to persist in the throat of asymptomatic carriers.

Adhesins, Bacterial↗

Effect of a multidisciplinary program of weight reduction on endothelial functions in obese women.

Obesity is associated with an increased risk of developing atherosclerosis and atherosclerotic lesions are essentially an inflammatory response. The aim of this study was to evaluate the effect of a medically supervised, multidisciplinary weight loss program on endothelial functions and circulating levels of proinflammatory cytokines in obese women. Twenty healthy pre-menopausal obese women and 20 age-matched normal weight women were studied. Endothelial functions were assessed by evaluating the response of blood pressure and platelet aggregation to an intravenous bolus of L-arginine (3 g), the natural precursor of nitric oxide. In obese women, the vascular and rheological responses to L-arginine were significantly lower (p < 0.05) at baseline, as compared with non-obese women, indicating endothelial dysfunction; on the contrary, basal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were significantly higher (p < 0.01). After one year of a multidisciplinary program of weight reduction consisting of diet, exercise and liposuction surgery, all obese women lost at least 10% of their original weight (10.5 +/- 1.7 kg, range 7.9-13.9 kg). Compared with baseline, sustained weight loss was associated with reduction of cytokine (p < 0.01) concentrations and with improvement of vascular responses to L-arginine. In conclusion, a multidisciplinary approach aimed at inducing a sustained reduction of body weight in obese women is feasible and is associated with improvement of endothelial functions and reduction of circulating proinflammatory cytokine concentrations.

Adult↗

Association of tau gene polymorphism with Parkinson's disease.

We investigated the segregation of the dinucleotide GT repeat polymorphism in the intron between exons 9 and 10 of the tau gene in 300 patients with Parkinson's disease (PD) and in 197 normal controls. The A3 allele was more frequent in cases than in controls (30% versus 16%, p<0.001), and individuals carrying at least one A3 allele in their genotype had an increased risk of developing PD (odds ratio 2.78, 95% confidence interval 1.81-4.29). No significant differences were found between patients by considering the age at onset and the presence of family history or dementia. Our findings suggest a possible involvement of the tau gene in the pathogenesis of PD.

Age of Onset↗

Verapamil inhibits interleukin-6 and vascular endothelial growth factor production in primary cultures of keloid fibroblasts.

An increased secretion of cytokines and growth factors has been hypothesised to play a role in the abnormal growth of keloid fibroblasts. The aim of this study was to evaluate the effect of the calcium antagonist verapamil on the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion, as well as on cellular growth, in primary cultures of fibroblasts derived from the central part of keloid lesions. These cells grew faster than peripheral keloid and nonkeloid fibroblasts, and, in long-term cultures, became stratified assuming a three-dimensional structure. Compared with peripheral and nonkeloid fibroblasts, central keloid fibroblasts presented an increased production of both IL-6 and VEGF (P<0.03 and P<0.005, respectively). Verapamil (100 microM) decreased IL-6 and VEGF production (P<0.03 and P<0.005, respectively) in central keloid fibroblasts cultures at 72 h. Moreover, verapamil decreased cellular proliferation by 29% and increased apoptosis to an absolute value of 8%. The results of this study demonstrate that in primary cultures of central keloid fibroblasts verapamil reduces the sustained basal IL-6 and VEGF production and inhibits cell growth; these data may offer the link with the beneficial effect of calcium antagonists on keloid scars in vivo.

Analysis of Variance↗

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

Analysis of Variance↗