The metabolism of gluconate in Escherichia coli. The subsidiary system and the nature of the gntS gene

The transport and phosphorylation of gluconate in E. coli occurs through two systems (GntI and GntII) which duplicate activities. bioH-asddeletion mutants do not grow on media with gluconate as sole carbon source because they lack the GntI system and do not express GntII. Although E. coli C177 is a Δ(bioH-asd) mutant, it carries the pyrB linked mutation gnt177 that enables it to metabolize this substrate through inducible expression of the GntII system. Several gntS derivatives which are unable to grow on gluconate were isolated from E. coli C177 by spontaneous curing of the transposon Tn10 previously inserted at the gntS locus (zjf::Tn10, min 95.3). A representative gntS mutant, E. coli TI141A retained the ability to take up gluconate but had lost the thermosensitive gluconokinase activity (gene gntV, min 96.9). Furthermore, it could be demonstrated that gntV is repressed in E. coli TI141A. The results indicate that gntS might specify a trans-acting positive regulator involved in the control of at least the expression of the thermosensitive gluconokinase (GntII), instead of a gluconate uptake system as it was previously postulated. Likewise, these results can be used to reconsider whether the locus altered by the gnt177 lesion is allelic with that of the GntII permease instead of a regulator, as it was originally postulated.     

Prevalence and mortality of patients with palliative needs in an acute respiratory setting

IntroductionNECPAL is a tool for identification of patients with advanced chronic disease in need of palliative care. The main objective of the study is to know the prevalence of patients with palliative needs in an acute respiratory ward in a Spanish tertiary hospital using NECPAL. A second objective of the study is to know the annual mortality rate of these patients.Materials and methodsCross sectional study and prospective monitoring of a cohort identified as palliative patients with the NECPAL tool for 12 months. Patient identification was performed in patients admitted to the respiratory ward of our hospital for longer than 3 days. We have assessed the annual vital status (deceased or not deceased) of patients and have recorded demographics, clinical and functional data, as well as the use of healthcare resources.ResultsWe monitored a cohort of 363 patients. Of them, 87 patients (24.3%) (IC 95% 19–30) were identified as NECPAL positive. 60% of patients (n = 64) died within 12 months of their admission. There was no significant difference in the mortality ratio of oncologic versus non oncologic patients. In a multivariable analysis, mortality was associated with demand by patients or relatives for palliative care and with the presence of specific disease progression markers or indicators.Conclusionsprevalence of patients with palliative needs in acute respiratory wards is high (one out of four patients). 60% of the patients identified as NECPAL positive in our cohort died in the first 12 months. Training of healthcare professionals as well as availability of appropriate resources are indispensable factors to improve care of this population.     

Comparison of High Ribavirin Induction Versus Standard Ribavirin Dosing, Plus Peginterferon-α for the Treatment of Chronic Hepatitis C in HIV-Infected Patients: The PERICO Trial

Background.?Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. Methods.?HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180?μg/d) plus either RBV standard dosing (1000 or 1200?mg/d if <75 or ≥75?kg, respectively) or RBV induction (2000?mg/d) along with subcutaneous erythropoietin β (450?IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. Results.?A total of 357 patients received ≥1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14?μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3?mg/dL; P?相似文献   

Auricular perichondritis in adults. An evaluation-study of 12 hospitalized patients

Perichondritis of the auricle in adults can be secondary to traumatic agents, external otitis or surgery being Pseudomona aeruginosa the bacteria more often isolated. We have performed a retrospective study of 12 hospitalized patients with that diagnosis and these following variables have been evaluated: Age, sex, personal antecedents, clinical symptoms, affected auricle, complementary explorations, treatment, evolution and stay.     

Mutations in the hereditary haemochromatosis gene HFE in professional endurance athletes

Background: Hereditary haemochromatosis, a disease that affects iron metabolism, progresses with a greater or lesser tendency to induce iron overload, possibly leading to severe organ dysfunction. Most elite endurance athletes take iron supplements during their active sporting life, which could aggravate this condition.

Objective: To determine the prevalence and discuss potential clinical implications of mutations of HFE (the gene responsible for hereditary haemochromatosis) in endurance athletes.

Methods: Basal concentrations of iron, ferritin, and transferrin and transferrin saturation were determined in the period before competition in 65 highly trained athletes. Possible mutations in the HFE gene were evaluated in each subject by extracting genomic DNA from peripheral blood. The restriction enzymes SnaBI and BclI were used to detect the mutations 845G→A (C282Y) and 187C→G (H63D).

Results: Our findings indicate a high prevalence of HFE gene mutations in this population (49.2%) compared with sedentary controls (33.5%). No association was detected in the athletes between mutations and blood iron markers.

Conclusions: The findings support the need to assess regularly iron stores in elite endurance athletes.

     

Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus coeruleus neurons

1 The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings. 2 In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg(-1), i.p. and 100 micro g, i.c.v.) or valldemossine (10 mg kg(-1), i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group. 3 After chronic administration of 2-BFI (10 mg kg(-1), i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg(-1), i.p.) or valldemossine (10 mg kg(-1), i.p.) were used. 4 Acute administration of 2-BFI (10 and 40 mg kg(-1), i.p. and 100 micro g, i.c.v.) but not valldemossine (40 mg kg(-1), i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED(50) values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met(5)-enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 micro M) was applied to rat brain slices (EC(50) increased by 5.6; P<0.05). 5 The present data demonstrate that there is an interaction between 2-BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2-BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance.     

Efficacy of amoxicillin/clavulanic acid in preventing infectious and inflammatory complications following impacted mandibular third molar extraction.

OBJECTIVE: To find out whether the frequency of postoperative infectious and inflammatory complications (IC) in subjects treated with placebo (Pl) is greater than those treated with antibiotic (Ab) after extraction of an impacted mandibular third molar (M3). Our hypothesis is there are more IC in Pl than in Ab, with a maximum ratio difference of 0.067. STUDY DESIGN: A double-blind placebo-controlled randomized clinical trial. The sample was derived from the population of subjects attending Cruces Hospital for evaluation and extraction of 1 M3 under local anesthesia. Patients were treated with postoperative placebo or amoxicillin/clavulanic acid 500/125 mg 3 times a day during 4 days. The outcome variable was infectious and inflammatory complications. Sex, age, smoking, molar depth, angulation, need for sectioning, ostectomy, and operation time were recorded. Analysis was by intention to treat, risk measures, and logistic regression. RESULTS: In 490 subjects (259 Ab and 231 Pl), the frequency of IC was 1.9% in the Ab and 12.9% in the Pl group (OR 7.6, 95%CI 2.9-19.9; P < .001). The number needed to treat was 10 (7-16). Unadjusted relative risk was 0.15 (0.06-0.38) (P < .001). Absolute reduction risk was 0.11(0.066-0.155)]. Therefore, the hypothesis cannot be rejected. Multivariate analysis shows treatment with antibiotic (OR = 8.66 (3.17-23.67); P < .001) and age (OR = 1.08 (1.00-1.16); P = .029) are the only variables to be included in the logistic regression model. CONCLUSION: Amoxicillin/clavulanic acid is efficacious in reducing the incidence of IC following third molar extraction but should not be prescribed in all cases.