Designing a new scoring system (QualyP Score) correlating the management of cardiopulmonary bypass to postoperative outcomes.

AIM: The aim of this study was to ascertain if a score, directly derived from CPB records, could correlate to major postoperative outcomes. METHODS: An additive score (QualyP Score) was created from 10 parameters: peak lactate value during CPB, peak VCO(2)i, lowest DO(2)i/VCO(2)i, peak respiratory quotient, CPB time, cross-clamp time, lowest CPB temperature, circulatory arrest, ultrafiltration during CPB, number of packed red cells transfused intraoperatively. The PerfSCORE was calculated, as well. Multivariable logistic regression models were built to detect the independent predictors of: peak lactate >3 mmol/L during the first three postoperative days; the incidence of acute kidney injury network (AKIN) 1-2-3; respiratory insufficiency; mortality. RESULTS: The mean score was 4.8±2.6 (0-10). A QualyP Score ≥1 was predictive of postoperative acidosis (OR=1.595). A score ≥2 was predictive of AKIN 2 (OR=1.268) and respiratory insufficiency (OR=1.526). A score ≥5 was predictive of AKIN 3 (OR=1.848) and mortality (OR=1.497). CONCLUSIONS: QualyP Score may help to provide a quality marker of perfusion, emphasizing the need for goal-directed perfusion strategies.

Molecular basis of agonist docking in a human GPR103 homology model by site-directed mutagenesis and structure-activity relationship studies.

BACKGROUND AND PURPOSE: The neuropeptide 26RFa and its cognate receptor GPR103 are involved in the control of food intake and bone mineralization. Here, we have tested, experimentally, the predicted ligand-receptor interactions by site-directed mutagenesis of GPR103 and designed point-substituted 26RFa analogues. EXPERIMENTAL APPROACH: Using the X-ray structure of the ß2 -adrenoceptor, a 3-D molecular model of GPR103 has been built. The bioactive C-terminal octapeptide 26RFa(19-26) , KGGFSFRF-NH2 , was docked in this GPR103 model and the ligand-receptor complex was submitted to energy minimization. KEY RESULTS: In the most stable complex, the Phe-Arg-Phe-NH2 part was oriented inside the receptor cavity, whereas the N-terminal Lys residue remained outside. A strong intermolecular interaction was predicted between the Arg(25) residue of 26RFa and the Gln(125) residue located in the third transmembrane helix of GPR103. To confirm this interaction experimentally, we tested the ability of 26RFa and Arg-modified 26RFa analogues to activate the wild-type and the Q125A mutant receptors transiently expressed in CHO cells. 26RFa (10(-6) M) enhanced [Ca(2+) ]i in wild-type GPR103-transfected cells, but failed to increase [Ca(2+) ]i in Q125A mutant receptor-expressing cells. Moreover, asymmetric dimethylation of the side chain of arginine led to a 26RFa analogue, [ADMA(25) ]26RFa(20-26) , that was unable to activate the wild-type GPR103, but antagonized 26RFa-evoked [Ca(2+) ]i increase. CONCLUSION AND IMPLICATIONS: Altogether, these data provide strong evidence for a functional interaction between the Arg(25) residue of 26RFa and the Gln(125) residue of GPR103 upon ligand-receptor activation, which can be exploited for the rational design of potent GPR103 agonists and antagonists.

Antimicrobial susceptibility and beta-lactamase production of anaerobic and aerobic bacteria isolated from pus specimens from orofacial infections.

Most suppurative orofacial infections are polymicrobial. Information regarding the antimicrobial susceptibility of the microorganisms involved can be useful in the choice of an effective antibiotic therapy. In this study we determined the antimicrobial susceptibility of a total 235 anaerobic and aerobic bacteria recently isolated from pus specimens of orofacial infections. All the viridans streptococci were susceptible to penicillin, cefotaxime, cefoxitin, imipenem and levofloxacin. Imipenem and levofloxacin were active against 100% of the anaerobic Gram-positive organisms isolated. Among the anaerobic Gram-negative rods beta-lactamase production was detected in all species except Campylobacter rectus. Amoxicillin-clavulanate, cefoxitin, imipenem and metronidazole were active against all the isolates of anaerobic Gram-negative species. Isolates resistant to erythromycin were found in all the species tested, however, resistance to clindamycin was only detected in Porphyromonas gingivalis and Bacteroides ureolyticus. Isolates resistant to levofloxacin were detected in P. gingivalis and Prevotella sp.

Dental implants with locking taper connection versus screwed connection: microbiologic and scanning electron microscope study.

The aim of this study is to carry out an analysis of the Fixture-Abutment Interfaces (FAI), comparing different connection systems, to evaluate the role of geometric discrepancy, which is present between the abutment and the fixture, in favoring the permeability to bacterial colonization. Two types of commercially available FAI were studied, 16 screwed FAI (Sweden-Martina Italia) (4 of Ø 3.8 mm diameter, 4 of Ø 4.7 mm diameter, 4 of Ø 5.7 mm diameter and 4 of Ø 6.7 mm diameter) and 4 FAI (Bicon) (Ø 3.5mm diameter). The assays were carried out in vitro, placing the different dental implants in contact with broth culture of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Streptococcus pyogenes to test the infiltration inside the FAI. Furthermore, scanning electron microscope (SEM) analysis was carried out to evaluate the gap at the fixture-abutment interface. In all the locking taper FAI and in the screwed FAI with a diameter of 3.8 mm there was no trace of bacterial infiltration of the species examined. In the screwed FAI with a diameter of 4.7 mm, 5.7 mm and 6.7 mm there was an increasing level of bacterial infiltration in relationship to the diameter. Therefore, this paper shows that there exists an important correlation between the diameter of the screwed implant and the permeability to microbic infiltration that is directly proportional to the diameter of the implant.

Activity of Berberis aetnensis root extracts on Candida strains.

The antifungal activity of methanolic extract and alkaloidal fraction of Berberis aetnensis against Candida species was investigated. The crude extract was active against Candida species, this activity being higher than that of the alkaloidal fraction and berberine.

Comparison of systemic flurithromycin therapy and clinical procedures in the treatment of periodontal diseases.

The purpose of the present investigation was to evaluate, in 20 periodontal patients, the microbial and clinical effects of flurithromycin therapy plus scaling and root planning (SRP) in comparison with SRP alone. Clinical assessments of plaque, bleeding on probing and pocket depth were made prior to SRP alone and SRP plus flurithromycin therapy (375 mg twice daily for 5 days) and after both treatments. Subgingival plaque samples (n. 180) were taken prior to and after both treatments and analyzed by conventional bacteriological procedures. Differences in pocket depth and prevalence of bacterial species were analyzed pre- and post-therapies using statistical analyses. A significant decrease (p<0.001) was seen for pocket depth post SRP alone and post SRP plus flurithromycin. After two treatments, Actinobacillus actinomycetemcomitans, Bacteroides forsythus and Prevotella melaninogenica were eradicated from all tested sites. If we compare the prevalence of the species isolated after SRP alone and after SRP plus flurithromycin statistically significant differences were detected for P. gingivalis and for Fusobacterium nucleatum (p<0.05 and p<0.01, respectively). Flurithromycin can be considered a useful adjunct to mechanical periodontal treatment since it is more efficient in eliminating periodontal pathogens.

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.

Antibacterial activity of medicinal plant extracts against periodontopathic bacteria.

This study was performed to evaluate the antibacterial activity of Althaea officinalis L. roots, Arnica montana L. flowers, Calendula officinalis L. flowers, Hamamelis virginiana L. leaves, Illicium verum Hook. fruits and Melissa officinalis L. leaves, against anaerobic and facultative aerobic periodontal bacteria: Porphyromonas gingivalis, Prevotella spp., Fusobacterium nucleatum, Capnocytophaga gingivalis, Veilonella parvula, Eikenella corrodens, Peptostreptococcus micros and Actinomyces odontolyticus. The methanol extracts of H. virginiana and A. montana and, to a lesser extent, A. officinalis were shown to possess an inhibiting activity (MIC < or = 2048 mg/L) against many of the species tested. In comparison, M. officinalis and C. officinalis extracts had a lower inhibiting activity (MIC > or = 2048 mg/L) against all the tested species with the exception of Prevotella sp. Illicium verum methanol extract was not very active though it had a particular good activity against E. corrodens. The results suggest the use of the alcohol extracts of H. virginiana, A. montana and A. officinalis for topical medications in periodontal prophylactics.

Faropenem, a new oral penem: antibacterial activity against selected anaerobic and fastidious periodontal isolates.

The in vitro activity of faropenem, an oral penem, was compared with those of penicillin, co-amoxiclav, cefoxitin, clindamycin, erythromycin and metronidazole against 106 isolates of anaerobic pathogens involved in systemic infections. The organisms tested comprised Porphyromonas gingivalis (29), Prevotella spp. (eight), Prevotella melaninogenica (seven), Prevotella intermedia (five), Actinomyces spp. (25), Fusobacterium nucleatum (14), Peptostreptococcus spp. (11), Bacteroides ureolyticus (five) and Bacteroides forsythus (two). The antimicrobial properties of faropenem were investigated by studying MICs, MBCs, time-kill kinetics and post-antibiotic effect (PAE). Faropenem was highly active against all the anaerobes tested (MIC(90) < or = 0.5 mg/L) and was bactericidal against both beta-lactamase-positive and -negative anaerobes, with a maximum bactericidal effect at 10 x MIC at between 12 and 24 h. In addition, faropenem had an in vitro PAE on all the tested isolates and this was not influenced by beta-lactamase production. Faropenem may be useful for treating infections caused by periodontal bacteria or oral flora.

Antibacterial activity of moxifloxacin against periodontal anaerobic pathogens involved in systemic infections.

The in vitro activity of moxifloxacin was compared with that of penicillin G, amoxycillin/clavulanate, cefoxitin, erythromycin, clindamycin and metronidazole against 158 isolates associated with periodontal infections. MIC(50)/MIC(90) values of moxifloxacin were respectively 0.06/0.5 mg/l for Porphyromonas gingivalis (35), for Prevotella spp. (28) and Actinomyces spp. (35), 0.12/0.25 mg/l for Fusobacterium nucleatum (20) and 0.06/0.12 mg/l for Peptostreptococcus spp. (30). The minimum inhibitory concentration (MIC) range of moxifloxacin for Bacteroides forsythus (6) and Campylobacter rectus (4) was 0.06-0.12 mg/l. The minimum bactericidal concentrations were equal to or 2-4 times the MIC values. Moxifloxacin produced a bactericidal effect at 8 h. Our results show that moxifloxacin has good antibacterial activity against periodontal pathogens comparable with that of cefoxitin and amoxycillin/clavulanate, and better than that of clindamycin, metronidazole and penicillin.

Minimal inhibitory concentrations and time-kill determination of moxifloxacin against aerobic and anaerobic isolates.

Moxifloxacin is a new oral 8-methoxy-quinolone with a wide spectrum of activity against Gram-negative and anaerobic bacteria, atypical micro-organisms and multi-resistant Gram-positive bacteria. This study was designed to assess the in vitro activity of moxifloxacin against Gram-positive bacteria with different resistance patterns, anaerobes and atypical micro-organisms such as Chlamydia and Mycoplasma. Moxifloxacin had good activity against Streptococcus pneumoniae with all strains inhibited by < or =0.12 mg/l. The minimal inhibitory concentrations (MICs) of moxifloxacin for Streptococcus pyogenes and Streptococcus agalactiae ranged from 0.03 to 0.5 mg/l while those of ciprofloxacin were about two- to four-fold higher (MICs=0.12-1 mg/l). Moxifloxacin was poorly active against enterococci but its activity against Clostridium and Bacteroides spp. was in the same range as that of metronidazole and superior to that of clindamycin. Moxifloxacin was substantially more active than both ciprofloxacin and sparfloxacin against Chlamydia.

Antibacterial activity and post-antibiotic effect of flurithromycin compared with other macrolides and penicillins against periodontal pathogens.

In this study the authors examined the activity of flurithromycin compared to that of erythromycin, spiramycin and penicillin against 107 strains of various species supposed to cause periodontitis. The range of MICs of flurithromycin was: < or =0.06-2 mg/l for P. gingivalis (28 isolates), 0.06-2 mg/l for P. melaninogenica (7), 0.5-4 mg/l for P. intermedia (5), 0.25-8 mg/l for Prevotella sp. (8), 1-16 mg/l for F. nucleatum (14), 0.12-0.5 mg/l for W. recta (2), 0.5-32 mg/l for E. corrodens, 0.5-2 mg/l for B. forsythus (2); < or =0.06-64 mg/l for Peptostreptococcus sp. (11), < or =0.06-1 mg/l for A. odontolyticus (11) and for A. naeslundii (7) and < or =0.06-16 mg/l for A. viscosus (7). Macrolide activity was ranked in decreasing order from flurithromycin to erythromycin to spiramycin. Beta-lactamase production was demonstrated in Prevotella sp. (20%) and in F. nucleatum (7%). Isolates which were beta-lactamase negative but resistant to penicillin were found among Peptostreptococcus sp. and Actinomyces sp. A post-antibiotic effect of 2 hours was seen for flurithromycin on P. gingivalis and E. corrodens. The good in vitro activity of flurithromycin against bacteria supposed to cause periodontitis suggests clinical potential in the treatment of these diseases.

Solution structure of microcin J25, the single macrocyclic antimicrobial peptide from Escherichia coli.

The three-dimensional solution structure of microcin J25, the single cyclic representative of the microcin antimicrobial peptide class produced by enteric bacteria, was determined using two-dimensional 1H NMR spectroscopy and molecular modeling. This hydrophobic 21-residue peptide exhibits potent activity directed to Gram-negative bacteria. Its primary structure, cyclo(-V1GIGTPISFY10GGGAGHVPEY20F-), has been determined previously [Blond, A., Péduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthélémy, M., Prigent, Y., Salomón, R.A., Farías, R.N., Moreno, F. & Rebuffat, S. (1999) Eur. J. Biochem., 259, 747-755]. Conformational parameters (3JNHCalphaH coupling constants, quantitative nuclear Overhauser enhancement data, chemical shift deviations, temperature coefficients of amide protons, NH-ND exchange rates) were obtained in methanol solution. Structural restraints consisting of 190 interproton distances inferred from NOE data, 11 phi backbone dihedral angle and 9 chi1 angle restraints derived from the coupling constants and three hydrogen bonds in agreement with the amide exchange rates were used as input for simulated annealing calculations and energy minimization in the program XPLOR. Microcin J25 adopts a well-defined compact structure consisting of a distorted antiparallel beta sheet, which is twisted and folded back on itself, thus resulting in three loops. Residues 7-10 and 17-20 form the more regular part of the beta sheet. The region encompassing residues Gly11-His16 consists of a distorted beta hairpin, which divides into two small loops and is stabilized by an inverse gamma turn and a type I' beta turn. The reversal of the chain leading to the Phe21-Pro6 loop results from a mixed beta/gamma turn. A cavity, in which the hydrophilic Ser8 side-chain is confined, is delimited by two crab pincer-like regions that comprise residues 6-8 and 18-1.

Comparative activity of cefodizime and ceftriaxone against respiratory pathogens in an in vitro pharmacodynamic model simulating concentration-time curves.

The duration of time that serum levels are above the minimum inhibitory concentration (MIC; T >MIC) seems to be an important pharmacodynamic parameter for beta-lactams. The aim of this study was to evaluate the bactericidal activity of cefodizime and ceftriaxone in a pharmacokinetic model mimicking the concentrations in bronchial mucus and in serum (total and free) obtained at 2, 4, 8, 12 and 24 h, after 1 g i.m. administration once daily. The species investigated were respiratory pathogens (1 strain of Staphylococcus aureus, 2 strains of Streptococcus pneumoniae, 1 strain b-lactamase negative and 1 strain beta-lactamase positive of Haemophilus influenzae, 1 strain of Escherichia coli and 1 strain of Klebsiella pneumoniae); MIC50s of the chosen strains were reported. In this in vitro model the concentrations (serum and bronchial mucus) for both antibiotics are generally at or above the MIC values of the tested strains until 24 hours. The killing curve showed rapid killing for both antibiotics: 99.9% killing (a 3-log reduction in growth) within 6 to 8 h, depending upon the microorganism tested. There was no significant difference in the log kill between cefodizime and ceftriaxone. These data confirm that T >MIC for beta-lactams is the pharmacodynamic parameter which best correlates with bactericidal efficacy. On the basis of the killing curve determined for cefodizime versus ceftriaxone at concentrations that these antibiotics can reach during therapy with 1 g i.m. once daily we expect reasonable clinical efficacy with monoadministration of cefodizime as well as for ceftriaxone in respiratory tract infections.

Efficacy and acceptability of transdermal estradiol in the treatment of postmenopausal bone loss.

In order to assess the effects and acceptability of transdermal estradiol on the prevention of the loss of bone mass, the Authors administered transdermal estradiol (ETTS 50 mcgr/day) for 3 weeks and, cyclically, medroxyprogesterone 10/mg/day from day 10 to day 21 of each cycle for 12 months, to 20 operated patients for bilateral ovariectomy. Primary markers of the bone turnover (hydroxyproline urinary, osteocalcin, PTH) were estimated before therapy and after 3, 6, 9, 12 months. The BMD was evaluated before therapy and after 6 and 12 months. Our study clearly shows that the transdermal administration of estradiol prevents the postmenopausal bone loss, also in postmenopausal women at higher risk of developing osteoporosis as those evaluated in our study.

Modifications of the bone turnover in operated patients of bilateral ovariectomy.

The most important factor responsible for osteoporosis postmenopausal is the loss of the oestrogen. For this reason we have estimated the modifications of the bone turnover in the operated patients for bilateral ovariectomy in fertile age by study of the BMD (bone mineral density) and of the various biohumoral parameters that are involved in the process of bone remodelling urinary hydroxyproline, osteocalcin). Our research consists of two phases. I phase: we have conducted a transverse study on a group of 43 patients subdivided in 3 subgroups on the basis of the years elapsed since they were operated. II phase: it is a longitudinal study. We have observed 6 women. We have estimated the turnover before the operation (T0) at (T1), at 30 (T2), at 90 (T3) and at 180 (T4) days from the operation. The results show that the sudden and rapid decrease of the oestrogenic rate determines a sudden increase of the bone turnover. The activity of the osteoblastic line is faster, the activity of osteoblastic line is slower. The beginning of the loss of the bone mass is about the 7% already at six months (longitudinal study), the loss of bone mass reaches the maximum within the first 2-3 years (about 16%) from the operation (transverse study).