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91.
Montemagni C Badà A Castagna F Frieri T Rocca G Scalese M Villari V Rocca P 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):137-145
Purpose
We explored socio-demographic and clinical variables associated with compulsory admissions (CA) compared with voluntary admissions in schizophrenia-spectrum patients; moreover, we investigated the ability of excitement, emotion perception, and lack of insight to predict CA.Methods
119 consecutive schizophrenia-spectrum patients admitted to the Servizio Psichiatrico di Diagnosi e Cura (SPDC = PES = psychiatric emergency service) of the Department of Neuroscience and Mental Health-San Giovanni Battista Hospital of Turin in the period between December 2007 and December 2009 were enrolled in the study. A backward stepwise logistic regression was used to test factors contributing to CA.Results
CA rate in our sample was 28.5%. Previous CAs, drop-out, severity of illness, positive symptoms, excitement, emotion perception, and insight were significantly different in CA patients compared to voluntary ones. After backward selection of variables, three variables predicted CA in our sample: excitement, impaired emotion perception and lesser insight. Finally, the effect of excitement on CA status seemed partially mediated by emotion perception, the prediction model accounting for 53.8% of the variance of CA status. Conversely, insight seemed not to be a mediator of excitement on CA.Implications
Understanding CA patterns in special populations represents a first step towards improving clinical decision-making and developing appropriate interventions and service-provision. 相似文献92.
Baptista F Barrigas C Vieira F Santa-Clara H Homens PM Fragoso I Teixeira PJ Sardinha LB 《Journal of bone and mineral metabolism》2012,30(1):100-108
In the context of physical education curricula, markers of physical fitness (e.g., aerobic capacity, muscular strength, flexibility,
and body mass index or body fat) are usually evaluated in reference to health standards. Despite their possible mediating
role in the relationship between weight-bearing or muscle forces and features of bone tissue, these attributes of fitness
may not be the most relevant to predict skeletal health. It is therefore important to analyze the relative contribution of
these factors to the variability in bone tissue of different parts of the skeleton, and to analyze it by gender, as sensitivity
to mechanical loading can diverge for boys and girls. We compared the effects of habitual physical activity (PA) and lean
mass, as surrogates of weight-bearing and muscle forces, and of physical fitness (aerobic and muscle capacity of lower and
upper limbs) on bone mineral content (BMC) and size of total body, lumbar spine, femoral neck, and 1/3 radius in 53 girls
and 64 boys from 7.9 to 9.7 years of age. After controlling for bone age, body mass, body height, and calcium intake, lean
mass was the most important predictor of bone size and/or mineral in both genders (p < 0.05), while habitual weight-bearing PA positively influenced BMC in boys (p < 0.05). The effect of muscle in bone was not determined by PA and fitness score did not explain bone variability. Femoral
neck was the bone site more closely associated with mechanical loading factors; boys with a PA > 608 counts/min/day (~105 min/day
of moderate and vigorous intensity) showed 13–20% more BMC than those with less physical activity, and girls with a lean mass
>19 kg showed 12–19% more BMC than those with less lean mass. These findings suggest that lean mass was the most important
predictor of bone size and/or mineralization in both genders, while habitual weight-bearing PA appears to positively impact
on bone mineral in prepubertal boys and that both lean mass and PA need to be considered in physical education curricula and
other health-enhancing programs. 相似文献
93.
Laurent Poirel Jean-Denis Docquier Filomena De Luca Annemie Verlinde Louis Ide Gian Maria Rossolini Patrice Nordmann 《Antimicrobial agents and chemotherapy》2010,54(1):533-535
A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ß-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The blaBEL-2 gene was identified from a P. aeruginosa isolate clonally related to another blaBEL-1-positive isolate.Extended-spectrum ß-lactamases (ESBLs), such as TEM, SHV, PER, VEB, GES, and more recently, CTX-M variants, are reported increasingly to be found in Pseudomonas aeruginosa in various areas (1, 2, 7, 8, 10-12, 15, 17, 21, 23, 27, 28, 30). The BEL-1 ß-lactamase, distantly related to other ESBLs, was identified from a P. aeruginosa isolate from Roeselare, Belgium, which interestingly shows resistance to ticarcillin and ceftazidime but only reduced susceptibility to piperacillin, cefepime, cefpirome, and aztreonam (24). The blaBEL-1 determinant was found as a gene cassette in the chromosome-borne class 1 integron, In120, that includes other resistance genes (aacA4, aadA5, and smr2) and that was part of a Tn1404-type transposon structure (24). Very recently, Bogaerts et al. (5) reported on the diffusion of BEL-1-producing isolates in various hospital centers of Belgium and also found that BEL-1 could be associated with other relevant β-lactamases, such as the VIM-1 metallo-β-lactamase (5).P. aeruginosa isolate 531 (this study) was recovered from a urine sample of a patient hospitalized in Roeselare, Belgium, in February 2007 for pneumonia and was resistant to all β-lactams but imipenem (Table (Table1).1). A synergy between aztreonam or ceftazidime and clavulanic acid-containing disks suggested the synthesis of an ESBL (19). PCR followed by sequencing using ESBL gene-specific primers (24) identified a novel gene encoding BEL-2, which differs from BEL-1 by a single amino acid substitution (Leu to Phe at Ambler position 162) (3). Transfer of a ß-lactam resistance marker from P. aeruginosa 531 to Escherichia coli or to P. aeruginosa reference strains was unsuccessful by either conjugation or transformation (25). Plasmid extraction performed as described previously (14) did not identify any plasmid, suggesting a chromosomal location of the blaBEL-2-like gene in P. aeruginosa 531. A pulsed-field gel electrophoresis (PFGE) analysis (4) showed that isolates 531 (BEL-2 positive) and 51170 (BEL-1 positive), recovered from the same geographical area, were clonally related. A PCR mapping approach confirmed the presence of a class 1 integron whose structure was identical to that of In120 of P. aeruginosa 51170 (24) and identified an identical structure in P. aeruginosa 531 (data not shown). Overall, these data suggest that the blaBEL-2 sequence likely resulted from a mutational event that had occurred in In120-carrying P. aeruginosa strains.
Open in a separate windowaMICs of β-lactams for P. aeruginosa 531 and 51170 clinical isolates, producing ESBLs BEL-2 and BEL-1, respectively, E. coli TOP10 harboring recombinant plasmid pSB-2 expressing BEL-2, E. coli TOP10 harboring recombinant plasmid pSB-1 expressing BEL-1, and the E. coli TOP10 reference strain.bCLA, clavulanic acid at a fixed concentration of 4 μg/ml; TZB, tazobactam at a fixed concentration of 4 μg/ml.In order to compare the contributions of BEL-1 and BEL-2 to ß-lactam resistance, the corresponding genes (amplified using primers PreBEL-A [5′-AGACGTAAGCCTATAATCTC] and PreBEL-B [5′-GCGAATTGTTAGACGTATG]) were cloned in the pCR-BluntII-TOPO vector (Invitrogen, Cergy-Pontoise, France) and subsequently introduced into E. coli TOP10, giving rise to recombinant strains E. coli TOP10(pSB-1) and E. coli TOP10(pSB-2), producing BEL-1 and BEL-2, respectively. MICs of ß-lactams were determined by solid agar dilutions following the guidelines of the CLSI (9). E. coli TOP10(pSB-2) had MICs of piperacillin, cephalothin, and cefuroxime that were lower than those of E. coli TOP10(pSB-1), but its cefotaxime, ceftazidime, ceftriaxone, and cefepime MICs were higher than those of TOP10(pSB-1), while MICs of carbapenems were the same (Table (Table11).E. coli TOP10(pSB-2) produced a ß-lactamase with a pI value of 7.1 (identical to that of BEL-1) (18). Approximately 1.5 mg of BEL-2 was purified (>95% as estimated by SDS-PAGE analysis; data not shown) from an E. coli MCT236(pET-BEL-2) crude extract by using a two-step chromatography process (an anion exchange at pH 7.5 using a Q Sepharose Fast Flow column followed by a cation exchange at pH 6.2 using a 1-ml Resource S column). (The specific activity was 8,800 nmol/min·mg of protein with 100 μM of cephalothin as the substrate, purified 95-fold.) BEL-2 had a broad-spectrum hydrolysis profile, including penicillins and expanded-spectrum cephalosporins but not cephamycins and carbapenems (Table (Table2).2). BEL-2 overall showed higher catalytic efficiencies (kcat/Km) than BEL-1 for aztreonam and most oxyiminocephalosporins (cefotaxime, ceftazidime, ceftriaxone, and cefepime but not cefuroxime). This was due to a significant alteration of the Km values for these substrates with BEL-2, which were decreased relative to those of BEL-1 by 300-fold (ceftriaxone) to up to three orders of magnitude (ceftazidime) (Table (Table2).2). Interestingly, a decrease of the Km value was also observed with all the other substrates (though the variation was less important), likely reflecting a modification of the active site structure and thus substrate recognition. Overall, BEL-2 kcat values were also lower but to a lesser extent (Table (Table2).2). The values of catalytic efficiency toward expanded-spectrum cephalosporins for BEL-2 may explain the higher MICs observed for the BEL-2-producing recombinant E. coli strains and P. aeruginosa clinical isolate. Position 162 is located at the beginning of the Ω loop, which bears the functionally important Glu166 residue, which is conserved in class A enzymes, and where mutations conferring extended-spectrum properties have been extensively reported in natural TEM and SHV variants (13). The presence of a bulky Phe residue in BEL-2 might modify the orientation of the Ω loop and the overall geometry of the active site. The further extension of the substrate profile as a consequence of a single substitution in the Ω loop observed with the BEL-2 variant may parallel that of other enzymes, e.g., CTX-M-19 (CTX-M-14 Pro167Ser variant) (26) or GES-2 (GES-1 Gly170Asn variant) (28). Inhibition studies showed that BEL-2 and BEL-1 are similarly inhibited by clavulanic acid, tazobactam, and sulbactam (50% inhibitory concentrations of 0.1, 2, and 3 μM, respectively).
Open in a separate windowaStandard deviations were below 15%. ND, not determinable, due to the initial rate of hydrolysis being too low. 相似文献
TABLE 1.
MICs of β-lactamsaβ-Lactam(s)b | MIC (μg/ml) | ||||
---|---|---|---|---|---|
P. aeruginosa 531 | P. aeruginosa 51170 | E. coli TOP10 (pSB-2) (BEL-2) | E. coli TOP10 (pSB-1) (BEL-1) | E. coli TOP10 | |
Amoxicillin | >512 | >512 | >512 | >512 | 4 |
Amoxicillin and CLA | >512 | >512 | 64 | 64 | 4 |
Ticarcillin | >512 | >512 | >512 | >512 | 4 |
Ticarcillin and CLA | >512 | 128 | 64 | 64 | 4 |
Piperacillin | 16 | 16 | 32 | 128 | 1 |
Piperacillin and TZB | 8 | 8 | 8 | 32 | 1 |
Cephalothin | >512 | >512 | 256 | 256 | 2 |
Cefuroxime | >512 | >512 | 32 | 128 | 2 |
Cefoxitin | 512 | 512 | 2 | 2 | 2 |
Ceftazidime | 256 | 32 | 128 | 16 | 0.06 |
Cefotaxime | 256 | 32 | 32 | 4 | 0.12 |
Cefepime | 16 | 4 | 1 | 0.25 | 0.06 |
Cefpirome | 64 | 16 | 0.5 | 0.25 | 0.06 |
Aztreonam | 64 | 32 | 16 | 16 | 0.12 |
Imipenem | 1 | 1 | 0.12 | 0.12 | 0.12 |
TABLE 2.
Kinetic parameters of purified ß-lactamase BEL-2, in comparison with previously reported values of BEL-1 (22)aß-Lactam | BEL-2 | BEL-1 | ||||
---|---|---|---|---|---|---|
kcat (s−1) | Km (μM) | kcat/Km (mM−1· s−1) | kcat (s−1) | Km (μM) | kcat/Km (mM−1· s−1) | |
Benzylpenicillin | 1.2 | 4 | 300 | 3 | 20 | 150 |
Piperacillin | 1.1 | 0.3 | 3,700 | 2 | 15 | 130 |
Cephalothin | 4.3 | 2 | 2,200 | 150 | 280 | 540 |
Cephaloridine | 1.2 | 8 | 150 | 30 | 130 | 230 |
Cefoxitin | <0.01 | ND | ND | <0.01 | ND | ND |
Cefuroxime | 0.88 | 12 | 73 | 10 | 40 | 250 |
Ceftriaxone | 0.2 | 0.1 | 2,000 | 25 | 30 | 830 |
Cefotaxime | 0.13 | 0.45 | 290 | 30 | 250 | 120 |
Ceftazidime | 0.03 | 0.64 | 47 | >1.5 | >700 | ND |
Cefepime | 0.003 | 0.3 | 10 | 1 | 150 | 7 |
Aztreonam | 0.1 | 0.36 | 280 | 10 | 100 | 100 |
Imipenem | <0.01 | ND | ND | <0.01 | ND | ND |
94.
Poly(ADPR)polymerase inhibition and apoptosis induction in cDDP-treated human carcinoma cell lines 总被引:1,自引:0,他引:1
Poly(ADPR)polymerases' (PARPs) inhibitors potentiate the cytotoxic effects of chemotherapeutic agents like alkylating compounds and TOPO I poisons, while their action in combination with cisplatin still needs investigation. In fact, one of the earliest responses to DNA single- or double-strand breaks is the synthesis of poly(ADP-ribose) (PAR) by PARPs; these enzymes are components of DNA repair machineries and substrates of caspases. Cisplatin (cDDP) yields intra- and inter-strand DNA cross-links and several proteins that recognise cDDP-induced DNA damage, such as p53, are also targets of poly(ADP-ribosyl)ation. We compared the effects of treatments with cDDP and the PARPs inhibitor PJ34 in p53 mutated carcinoma cell lines (HeLa, KB, HT29) that exhibited differential sensitivities to the drugs, in terms of cell growth inhibition and onset of apoptosis. In cDDP-resistant HT29 cells we determined: (i) PJ34 potentiation of cDDP-induced cell growth inhibition; (ii) an increment of PARP-1 automodification following cDDP treatment. In cDDP-sensitive HeLa cells, we found that the drug induced apoptotic cell death associated with caspase-dependent PARP-1 proteolysis. 相似文献
95.
96.
97.
98.
99.
Noviello S Ianniello F Leone S Esposito S 《The Journal of antimicrobial chemotherapy》2003,52(5):869-872
OBJECTIVES: Garenoxacin is a novel des-F(6)quinolone that has shown excellent antimicrobial activity against a wide range of clinically important microorganisms. In this study, its activity was examined, in comparison with that of other antimicrobial agents, by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens. METHODS: Overall, 200 bacterial strains were tested. The antimicrobial activity of garenoxacin was compared with that of ciprofloxacin, levofloxacin, moxifloxacin, amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, ceftriaxone, imipenem, erythromycin and clarithromycin. In addition, the bactericidal activity of garenoxacin, moxifloxacin, levofloxacin and ciprofloxacin was evaluated by time-kill analysis against four strains each of staphylococci [two methicillin-susceptible (MSSA) and two methicillin-resistant (MRSA)], pneumococci (two penicillin-susceptible and two penicillin-resistant) and Streptococcus pyogenes (two erythromycin-susceptible and two erythromycin-resistant). Antibiotics were tested at concentrations 1-8 x MIC. RESULTS: MIC90 values of garenoxacin for the MSSA and MRSA strains were 0.03 and 2 mg/L, respectively. Among all the quinolones tested, garenoxacin yielded the lowest MIC values against all pneumococci (MIC90 0.12 mg/L) irrespective of macrolide resistance; the rank order of activity was garenoxacin> moxifloxacin>levofloxacin>ciprofloxacin. Excellent activity was shown also against Haemophilus influenzae (MIC90 or= 3 log10 decrease in viable counts (cfu/mL) within 3 h at 4 x MIC, whereas a moderate, slower killing rate was observed versus streptococci. CONCLUSIONS: This investigational des-F(6)quinolone represents a promising alternative for the treatment of respiratory tract infections. 相似文献
100.
Giovanni Luca Tiscia Angelo Ostuni Nicola Cascavilla Filomena Cappucci Potito Scalzulli Cosima Battista Antonio Abrescia Filippo Aucella Caterina Buquicchio Maurizio Brigante Giovanna D’Andrea Bruno Di Paolo Giulio Giordano Barbara Infante Silvia Piano Prudenza Ranieri Livio Tullo Elvira Grandone 《Journal of thrombosis and thrombolysis》2018,46(2):174-179
Severe ADAMTS13 deficiency (activity?<?10%) is pathognomonic of thrombotic thrombocytopenic purpura. ADAMTS13 testing is time-consuming and unavailable in many hospitals. Recently, a seven-variables score named PLASMIC score, has been developed to stratify acute patients, based on their risk of having a severe ADAMTS13 deficiency. We present the application of this score in a cohort of patients referred to our Center. From 2012 to 2017, 42 patients with suspected thrombotic microangiopathies from 6 Centers were referred to Hemostasis and Thrombosis Center of “Casa Sollievo della Sofferenza” Hospital/Research Institute for ADAMTS13 testing. For all patients, relevant medical and laboratory information were collected. To obtain the statistical measure of the discriminatory power of PLASMIC scoring system, the Area Under the Curve Receiver Operating Characteristic (AUC ROC) was calculated. We were able to calculate the PLASMIC score in 27 out of 42 patients; we found a good discrimination performance of the score with a resulting AUC value of 0.86 (95% CI 0.71–1.0; p?=?0.015). All patients but one with a high risk PLASMIC score (6–7) showed a severe deficiency. Among patients belonging to the intermediate risk (PLASMIC score 5) group, 2 showed normal ADAMTS13 activity and 2 levels below 10%. In none of the patients in the low risk group (PLASMIC score 0–4), a severe ADAMTS13 deficiency was found. Present results confirm and extend previous data regarding the predictive value of the PLASMIC score. Indeed, it shows a good diagnostic performance and can be useful for decision makers to properly and promptly define the better therapeutic approach. 相似文献