Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis

The antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) of Mycobacterium tuberculosis, but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treated M. tuberculosis were tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-N-oxide (DMPO) as spin traps. M. tuberculosis killing by RIF stimulated an increase in the rate of formation of the CPH radical (CP·). Lysate pretreatment with the O₂·⁻ and ·OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP· formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP· did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for ·OH and O₂·⁻, with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O₂·⁻-mediated mechanisms producing ·OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part in M. tuberculosis killing by the drug.     

Laser in dentistry. Characteristics and utilization

Authors present this review article in the beginning of an experimental study about lasers applications in dentistry. They also show the main characteristics of lasers involved in this kind of research.     

Birth delivery trauma and malocclusion

The aim of the investigation was to determine the dynamic of birth delivery and relate to dental occlusion among a group of adult subjects. The group studied was made up of 106 subjects (57 females and 49 males) referred for dental diagnosis and treatment. The average age was 26 with a range 22 to 30 years. In data collection and analysis the following were used as measures: dental occlusion (Angle Class I, II div 1, II div 2 and III) and type of delivery (normal, short, long, caesarean and other). Results showed that among 106 subjects 72 (68%) had malocclusion versus 34 (32%) with normal occlusion; 24 subjects (22.6%) have been normal delivery versus 82 (77.4%) with non-normal delivery. Class I is present in 34 subjects (32%), class II division 1 in 26 (24%), class II division 2 in 22. (20%), class III in 16 (14%), and 8 subjects (6%) fall in the section "other". Among 24 subjects with normal delivery 100% presented class I occlusion. However, among 82 subjects with non-normal delivery 10 subjects had a class I (12.2%) and the 72 (87.8%) had in the other classes, are distributed in the various subgroups of non-normal labor/delivery. None of the subjects with a malocclusion have a normal labor/delivery. Better understanding of the connections among osteopathic theory, craniosacral treatment and the outcomes upon dental occlusion, more rigorous evaluations are warranted.     

Self-adaptive robot training of stroke survivors for continuous tracking movements

Background  

Although robot therapy is progressively becoming an accepted method of treatment for stroke survivors, few studies have investigated how to adapt the robot/subject interaction forces in an automatic way. The paper is a feasibility study of a novel self-adaptive robot controller to be applied with continuous tracking movements.     

Integrating post induction WT1 quantification and flow-cytometry results improves minimal residual disease stratification in acute myeloid leukemia

Fifty uniformly treated adult AML patients were analyzed with respect to pre-treatment and post-induction risk factors. Forty-two patients achieving complete hematological remission were assessed for minimal residual disease (MRD) by WT1 gene expression; 34 by flow-cytometry (flow-MRD). Patients who were flow-MRD negative had a better 3-year disease-free (DFS; 79.5% vs. 27.3%; p = .032) compared with patients who were still positive after induction. Interestingly, DFS of flow-MRD positive patients was not related to the amount of flow-detected clone population (≥ or <1%, p = .41) but to WT1 reduction (ΔWT1, 3-year DFS; 46.2% vs. 0% if ΔWT1 was ≥ or < of 1.5 log, p = .001). In AML, combining MRD results provided by WT1 quantification and flow-cytometry improves the reliability of MRD-based prognostic stratification. Similar analyses by further larger studies should be advocated.     

Prognostic value of plasma renin activity in heart failure

The prognostic role of specific biomarkers of the renin-angiotensin-aldosterone system and sympathetic activation pathways in heart failure has never been investigated in populations with current evidence-weighted treatment. To establish whether the plasma renin activity (PRA), among several neurohormonal biomarkers, is able to predict cardiac events in a population of patients with heart failure on up-to-date treatment, we selected 996 consecutive patients with systolic left ventricular dysfunction (ejection fraction <50%, mean age 65 ± 13 years), who underwent a complete clinical and humoral characterization and were then followed up (median 36 months, range 0 to 72) for cardiac death and appropriate implantable cardioverter device shock. We recorded 170 cardiac deaths and 27 shocks. On Cox multivariate analysis, only ejection fraction (hazard ratio 0.962, 95% confidence interval 0.938 to 0.986), N-terminal pro-brain natriuretic peptide (NT-proBNP; hazard ratio 1.729, 95% confidence interval 1.383 to 2.161) and PRA (hazard ratio 1.201, 95% confidence interval 1.024 to 1.408) were independent predictors of cardiac death. Receiver operating characteristic curve analysis identified a cutoff value for PRA of 2.30 ng/ml/hour that best predicted cardiac mortality. Independent predictors of PRA were ejection fraction, functional class, sodium, potassium, NT-proBNP, norepinephrine, aldosterone, C-reactive protein, and medical therapy. The association of high NT-proBNP and high PRA identified a subgroup (22% of the study population) with the greatest risk of cardiac death. In conclusion, PRA resulted an independent prognostic marker in patients with systolic heart failure additive to NT-proBNP level and ejection fraction. PRA might help to select those patients needing an enhanced therapeutic effort, possibly targeting incomplete renin-angiotensin-aldosterone system blockade.     

Advanced glycation end products: possible link between metabolic syndrome and periodontal diseases

On a planetary scale, Metabolic Syndrome (MetS)is the third cause of inability after malnutrition and nicotinism, even higher than water shortage and sedentariness. In the USA, the prevalence is estimated at over 25 percent of the population; in Italy, it involves approximately 25 percent of men and even 27 percent of women. These are very high figures, corresponding to approximately 14 million affected individuals. The prevalence is alarming and must not be underestimated, particularly in the dental field, where more than one patient out of four sitting in a dentist chair is affected. The etiology of periodontal disease has not yet been clarified, and recently the idea to consider it as a multifactor pathology has been developed. Cofactors such as the formation of free radicals of oxygen (ROS), oxidative stress, lipid peroxidation, and formation of glycation end-products (AGEs) probably play an important role in the onset of periodontal disease. The AGEs are compounds physiologically produced by the cells. However, they accumulate and cause pro-inflammatory conditions, when the cellular clearance fails, or in hyperglycemic and oxidative states. All these conditions can be clinically summarized as Metabolic Syndrome. The purpose of this literature review is to establish a relationship between two pathologies with very high prevalence: Metabolic Syndrome and Periodontal Disorder. The literature seems to have clarified that MetS involves a pro-oxidation status, which induces AGE formation. AGEs play a very important role in the course and severity of periodontal diseases.