Clementina Cocuzza

Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: Evaluation of systemic and myocardial inflammatory response in a prospective randomized study.

OBJECTIVE This prospective randomized study sought to verify the systemic inflammatory response, inflammatory myocardial damage, and early clinical outcome in coronary surgery with the miniaturized extracorporeal circulation system or on the beating heart. METHODS Sixty consecutive patients were randomized to miniaturized extracorporeal circulation (n = 30) or off-pump coronary revascularization (off-pump coronary artery bypass grafting, n = 30). Intraoperative and postoperative data were recorded. Plasma levels of interleukin-6 and tumor necrosis factor-alpha were measured from systemic blood intraoperatively, at the end of operation, and 24 and 48 hours thereafter. Levels of the same markers and blood lactate were measured from coronary sinus blood intraoperatively to evaluate myocardial inflammation. Markers of myocardial damage were also analyzed. RESULTS One patient died in the off-pump coronary artery bypass grafting group. There was no statistical difference in early clinical outcome in both groups. Release of interleukin-6 was higher in the off-pump coronary artery bypass grafting group 24 hours after the operation (P = .03), whereas levels of tumor necrosis factor-alpha were not different in both groups. Cardiac release of interleukin-6, tumor necrosis factor-alpha, and blood lactate were not different in both groups. Release of troponin T was not significantly different in both groups. Levels of creatine kinase mass were statistically higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group, but only at the end of the operation (P < .0001). Hemoglobin levels were significantly higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group after 24 hours (P = .01). CONCLUSION Miniaturized extracorporeal circulation can be considered similar to off-pump surgery in terms of systemic inflammatory response, myocardial inflammation and damage, and early outcome.

New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens.

The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding pose of the newly synthesized compounds as compared with the crystallographic pose of linezolid, the 1,2,4-oxadiazole moiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interaction with U2585 is retained.

Prevalence and viral load of oncogenic human papillomavirus types associated with cervical carcinoma in a population of North Italy

A cross‐sectional study was carried out in a population of North Italy to determine the prevalence of eight oncogenic human papillomavirus (HPV) types most commonly found in cervical carcinoma and to study the relationship between HPV DNA loads and severity of disease. A total of 597 cervical samples obtained from patients with pathological findings (n = 472) and from women with normal cytology (n = 125) were analyzed by means of normalized Real‐time PCR assays to quantify HPV‐16, ‐18, ‐31, ‐45, and ‐33 group (including ‐33, ‐52, ‐58, ‐67); the normalization of oncogenic HPV viral load was carried out by quantitation of a single copy gene. The two most common oncogenic HPV types found were 16 and 31 (24.3% and 22.9% of pathological samples, respectively); multiple infections were demonstrated in 22% of pathological samples. Overall, the HPV total viral load was found to increase with increasing severity of associated lesions, although a stronger association was observed only for HPV‐31 and HPV‐16 (γ = 0.49 and 0.41, respectively) as compared to HPV‐18 and ‐33 group (γ = 0.19 and 0.02, respectively). However, we found that high levels of HPV‐31 or 33 group DNA could be prognostic of minor oncogenic risk for high‐grade squamous intraepithelial lesions (H‐SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively) than HPV‐16 and HPV‐18 (AORs = 30 and 8, respectively). The AORs also increased with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is a type‐dependent risk marker for the development of H‐SIL. J. Med. Virol. 81:278–287, 2009.

Quantitative Detection of Epstein-Barr Virus DNA in Cerebrospinal Fluid and Blood Samples of Patients with Relapsing-Remitting Multiple Sclerosis

The presence of Epstein-Barr Virus (EBV) DNA in cerebrospinal fluid (CSF) and peripheral blood (PB) samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS) and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC) positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.

Monocyclic β-lactams as antibacterial agents: Facing antioxidant activity of N-methylthio-azetidinones

A series of N-methylthio-β-lactams with antibacterial activity were thoroughly evaluated as antioxidants. We found that only the presence of a polyphenolic moiety anchored to the β-lactam ring ensured an adequate antioxidant potency. New compounds, efficiently combining in one structure antioxidant and antibacterial activity, may provide a promising basis for the development of new leads useful in adverse clinical conditions such as in cystic fibrosis patients, in whom colonization by MRSA and epithelial damage by chronic pulmonary oxidative stress take place.

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N-Thiomethylazetidinones

The increasing emergence of multidrug‐resistant microorganisms is one of the greatest challenges in the clinical management of infectious disease. New antimicrobial agents are therefore urgently required, particularly in the treatment of chronic and recurrent infections often associated with antibiotic‐resistant pathogens, as in the case of cystic fibrosis (CF) patients. This study reports the antibacterial activity of a series of monocyclic β‐lactams with an alkylidenecarboxyl chain or electron‐withdrawing groups such as 4‐OAc, 4‐SAc, and 4‐SO2Ph at the C4 position of the ring. N‐Unsubstituted and N‐thiomethyl derivatives were compared. A total of 33 azetidinones were tested for their activity against Gram‐positive and Gram‐negative bacterial clinical isolates. The combination of an N‐thiomethyl group and a benzyl ester on the 4‐alkylidene side chain were found to increase the potency against Gram‐positive bacteria. The N‐thiomethyl group clearly elevated the activity of 4‐acetoxyazetidinones relative to the corresponding NH derivatives. The most active compounds showed minimum inhibitory concentration (MIC) values of 4 and 8 mg L−1 against methicillin‐resistant Staphylococcus aureus isolated from pediatric patients with CF.

New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.

The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistant linezolid bacterial strains was higher than that of linezolid.

Antibacterial, Antimycotic and Trichomonicidal Activity of a New Nitroimidazole (EU 11100)

The antimicrobial profile of a new nitroimidazole derivative (5-nitro-1-methyl-imidazolyl-2-hydroxy-3 terbutylphenyl carbinol) has been studied. The in vitro activity of the new molecule has been evaluated against both aerobic and anaerobic bacteria, Trichomonas vaginalis, and mycetes, under suitable experimental conditions. The new compound was compared with ampicillin against aerobic bacteria; with metronidazole against anaerobic bacteria, lactobacilli and T. vaginalis; with nistatin and econazole against candida and with econazole and bifonazole against filamentous fungi. The new nitroimidazole derivative has been shown to be moderately active against some anaerobic bacteria belonging to both the Gram-positive and Gram-negative groups. Its inhibitory activity against T. vaginalis was similar to that of metronidazole.

Exploring the under-investigated “microbial dark matter” of drinking water treatment plants

Scientists recently reported the unexpected detection of unknown or poorly studied bacterial diversity in groundwater. The ability to uncover this neglected biodiversity mainly derives from technical improvements, and the term “microbial dark matter” was used to group taxa poorly investigated and not necessarily monophyletic. We focused on such under-investigated microbial dark matter of drinking water treatment plant from groundwater, across carbon filters, to post-chlorination. We tackled this topic using an integrated approach where the efficacy of stringent water filtration (10000 MWCO) in recovering even the smallest environmental microorganisms was coupled with high-throughput DNA sequencing to depict an informative spectrum of the neglected microbial diversity. Our results revealed that the composition of bacterial communities varies across the plant system: Parcubacteria (OD1) superphylum is found mainly in treated water, while groundwater has the highest heterogeneity, encompassing non-OD1 candidate phyla (Microgenomates, Saccharibacteria, Dependentiae, OP3, OP1, BRC1, WS3). Carbon filters probably act as substrate for microorganism growth and contribute to seeding water downstream, since chlorination does not modify the incoming bacterial community. New questions arise about the role of microbial dark matter in drinking water. Indeed, our results suggest that these bacteria might play a central role in the microbial dynamics of drinking water.

High HPV-51 Prevalence in Invasive Cervical Cancers: Results of a Pre-Immunization Survey in North Sardinia, Italy

Background Human Papilloma virus (HPV) is recognized as the etiological agent of benign and malignant ano-genital lesions. The most prevalent genotypes associated with cervical carcinoma are HPV-16 and -18 worldwide. However, recent studies have emphasized the role of other genotypes, such as HPV-51, in the pathogenesis of cervical dysplasia. The aim of the study was to estimate the burden of HPV-51 infection in invasive cervical malignant lesions in Northern Sardinia, Italy. Methods/Principal Findings An observational, retrospective, prevalence, mono-center study was carried out to evaluate the presence of HPV genotypes in tissues biopsies of cervical lesions (CIN-1, CIN-2, CIN-3 and invasive carcinoma) gathered from 1996 to 2009. Biological samples were collected from women admitted consecutively to a tertiary university hospital situated in Sassari, Italy. Molecular methods were used to identify 28 oncogenic HPV types. A total of 155 formalin-fixed and paraffin-embedded cervical tissue samples were analyzed. Approximately half of the cervical lesions were classified as invasive carcinoma. HPV-DNA was detected in 71% of the samples, with a higher frequency (100%) in those categorized as invasive neoplasia. Mono- or co-infections were demonstrated in 45.8% and 25.8% of the cervical samples, respectively. Overall, the most prevalent HPV types were -16 (49%) and -51 (19.4%), with an increased frequency of detection associated with the severity of the cervical lesions. Conclusions/Significance This survey highlights for the first time the relevant role of HPV-51 infection in the pathogenesis of invasive cervical cancer prior to the introduction of a vaccination program. Although a selection bias could have influenced the results, other recent studies have described the impact of HPV-51. This remarkable epidemiological element should be carefully evaluated, particularly in the view of opting for preventive vaccines, whose cross-protection patterns determine their efficacy in protecting against infection from HPV types that are not included in the vaccine itself.