Titanium Surface Chemical Composition Interferes in the Pseudomonas aeruginosa Biofilm Formation

Bacterial adhesion on three different surfaces: untreated Ti, plasma nitriding, and plasma carbonitriding Ti substrates were investigated. The samples were placed in bacterial cultures of Pseudomonas aeruginosa to assess biofilm formation. The correlation between the amount of bacteria attached to the surface after a lapse of time with nanotopography and physicochemical properties was performed. TiN showed the highest capacity to avoid bacterial adhesion, while presenting intermediate roughness and wettability. Although the surface of TiCN had the highest surface roughness and low contact angle (high wettability), bacterial adhesion was intermediate on this sample. Untreated Ti, even though presenting a smooth surface and low wettability, had the highest tendency to form biofilms.     

Global dissemination of a multidrug resistant Escherichia coli clone

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000–2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL–resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen.Many multidrug-resistant (MDR) bacterial strains are now recognized as belonging to clones that originate in a specific locale, country, or even globally. Escherichia coli sequence type 131 (ST131) is one such recently emerged and globally disseminated MDR pandemic clone responsible for community and hospital-acquired urinary tract and bloodstream infections. E. coli ST131 was identified in 2008 as a major clone linked to the spread of the CTX-M-15 extended-spectrum β-lactamase (ESBL) resistance (1–3). Since then, E. coli ST131 has also been strongly associated with fluoroquinolone resistance, and coresistance to aminoglycosides and trimethoprim-sulfamethoxazole (4–6). Alarmingly, strains of E. coli ST131 resistant to carbapenems have also been reported (7, 8), further limiting treatment options for this clone.E. coli ST131 belongs to the B2 phylogenetic subgroup I, with most isolates characterized as serotype O25b:H4 (1). Epidemiology studies using pulse-field gel electrophoresis (PFGE) have demonstrated that E. coli ST131 strains exhibit diversity, with some dominant PFGE pulsotypes including the UK epidemic strain A (9) and pulsotype 968 (10, 11) widely distributed across the globe. More recently, a typing scheme using the type 1 fimbriae fimH adhesin gene revealed that a large subclonal lineage of E. coli ST131 strains possess the FimH30 allele, which is also associated with specific mutations in the gyrA and parC genes that confer resistance to fluoroquinolones (12).Several whole genome (13–16) and PCR (1, 17–20) studies have revealed that E. coli ST131 strains possess a variable complement of genes encoding established virulence factors commonly associated with extraintestinal pathogenic E. coli (ExPEC). Indeed, few virulence genes appear to be uniformly present in E. coli ST131 and, thus, it is likely that differences in virulence gene content contribute to the variable virulence potential that has been reported. For example, although some ST131 strains cause rapid death in a mouse sepsis infection model (21), this phenotype is not consistent among all strains (22). The E. coli ST131 strain EC958, which is a representative of the FimH30-fluoroquinolone resistant subgroup, has been characterized at the molecular level (15). E. coli EC958 contains an insertion in the type 1 fimbriae regulator gene fimB (15) that is also common to other strains in the FimH30 subgroup (23) and colonizes the mouse bladder in a type 1 fimbriae-dependent manner (15). In mice, E. coli EC958 establishes acute and chronic urinary tract infection (UTI), forms intracellular bacterial communities in the bladder (24), and causes impairment of ureter contractility (25). E. coli EC958 is also resistant to the bactericidal action of human serum (26).The rapid global dissemination of E. coli ST131, combined with its MDR phenotype and the lack of new antimicrobial drugs in the developmental pipeline, highlights the urgent need to understand this pathogen and combat its spread. Here, we sequenced the genomes of 95 E. coli ST131 strains from six geographical regions (isolated from 2000 to 2011) to examine the spatial and temporal relationships of E. coli ST131. Our data supports the rapid and recent global dispersal of E. coli ST131 as a single clone.     

Reduction of Vmax by QX-314 and benzocaine in neonatal and adult canine cardiac Purkinje fibers

The authors have previously shown that the use-dependent action of lidocaine on the Vmax of canine Purkinje fibers and on intraventricular conduction in the in situ heart undergoes significant developmental changes. In this study, they use standard microelectrode techniques to test whether these age-related differences are due to the charged, more hydrophilic form or to the uncharged, more lipophilic form of a local anesthetic. QX-314, a permanently charged lidocaine derivative, depressed Vmax to a significantly greater extent in adult than in neonatal Purkinje fibers. This difference was due to its use-dependent blocking action and not to its tonic blocking action. The kinetic time constant (tau on) for the development of use dependence was shorter in adults (90 +/- 9 vs. 134 +/- 15 beats; P less than .05), whereas the time constant for recovery from use dependence (tau off) was shorter in neonates (53 +/- 4 vs. 106 +/- 10 sec; P less than .05). QX-314 (3 X 10(-5) M) shifted the curve of Vmax vs. activation voltage in a hyperpolarizing direction by 16.2 +/- 2.4 mV in adults and 5.1 +/- 1.1 mV in neonates (P less than .05). In contrast, the uncharged tertiary amine benzocaine (1 X 10(-5)-5 X 10(-4) M) showed no developmental differences in its effects on Vmax. Adult and neonatal fibers showed comparable tonic block and no use-dependent block. These results extend those of the authors' previous studies and suggest that developmental differences in the action of local anesthetics depend primarily on the use-dependent action of the charged molecular form.     

Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone

We compared the electrophysiologic, inotropic and antiarrhythmic properties of propafenone and two metabolites, 5-hydroxy (5-OH) propafenone and N-depropyl (N-DP) propafenone. In 18 canine Purkinje fibers with normal maximum diastolic potentials, all drugs (1 x 10(-8) to 1 x 10(-5) M) reduced action potential amplitude and duration. However, propafenone and 5-OH propafenone reduced Vmax in a use-dependent fashion at a lower concentration than N-DP propafenone. In 16 Purkinje fibers, slow response action potentials were induced by 22 mM K+ and isoproterenol, 1 x 10(-6) M. Vmax was comparably reduced by all compounds at 1 x 10(-5) M, but action potential amplitude was not affected by 5-OH propafenone. In 16 other Purkinje fibers in which automaticity at low levels of membrane potential was induced by BaCl2 (0.25 mM), only 5-OH propafenone was effective in slowing the automatic rate at therapeutic concentrations (3 micrograms/ml). In 15 guinea pig papillary muscles, all three drugs had negative inotropic effects at concentrations greater than or equal to 1 x 10(-6) M. In conscious dogs with sustained ventricular tachycardia 24 hr after infarction, we injected propafenone or a metabolite through an atrial cannula. At similar plasma levels, neither propafenone (n = 6) nor N-DP propafenone (n = 6) suppressed the arrhythmia, whereas 5-OH propafenone eliminated ventricular tachycardia in four of six dogs, and was more effective against monomorphic than polymorphic ventricular tachycardia. Hence, the two major metabolites of propafenone have important electrophysiologic effects, and 5-OH propafenone is more potent than the parent compound as a antiarrhythmic drug in the 24-hr Harris dog.     

Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson's disease and depression: effect on quality of life.

We assessed the effect of 3-month treatment of sertraline (50 mg) or low-dose amitriptyline (25 mg) on depression and quality of life in 31 patients with Parkinson's disease in a prospective single-blind randomized study. Both drugs significantly reduced the Hamilton Depression Rating Scale (HDRS-17) score. Completion rate was 75% for sertraline (12 of 16) and 73% for amitriptyline (11 of 15). Responder rate (HDRS-17 score reduction >/= 50%) was 83.3% for sertraline and 72.7% for amitriptyline. Sertraline but not amitriptyline treatment determined a significant benefit on quality of life (PDQ-39 scale). We found no change in Unified Parkinson's Disease Rating Scale scores. However, the improvement in specific PDQ-39 subscores (mobility, activities of daily living, and stigma) suggests that depression affects patient self-perception of motor function and further emphasizes the need for its treatment.     

Oculocerebrorenal Lowe syndrome: a literature review and two case reports

The present paper reviews the dental findings in oculocerebrorenal Lowe syndrome and presents two case histories. Reports of different patients are useful in order to enhance knowledge about the syndrome, because there are so many different oral manifestations.     

β‐globin cluster haplotypes in normal individuals and β039‐thalassemia carriers from Sardinia,Italy

Seven polymorphic sites in the β‐globin cluster in association with specific thalassemia mutations were analyzed in a sample from Sardinia, Italy. In order to verify previous works carried out on normal samples (β^A/β^A) and family studies on β‐thalassemia homozygotes individuals, the haplotype frequencies in both normal individuals (β^A/β^A) and β⁰39‐thalassemia carriers (β^A/β⁰) were studied. In our work chromosomes carrying β⁰39 mutation are characterized by a prevalence of haplotype II (? + + ? + + +) (52%) relative to haplotype I (+? ? ? ? + +) (29%), in contrast, among chromosomes with β^A the frequency of haplotype I is much greater than that of haplotype II. These data confirm what was found by other authors. Nevertheless, our results disagree with those of previous studies of Sardinians, both in frequencies values and in the numbers of haplotypes identified. Population analysis performed with samples carrying the β‐thalassemic mutation highlighted the peculiarity of Sardinians with respect to other Mediterranean populations. The Corsican population is most similar to the Sardinian population, confirming previous analyses performed with both classical markers and mitochondrial and genomic DNA. Am. J. Hum. Biol. 17:765–772, 2005. © 2005 Wiley‐Liss, Inc.