"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

The use of agomelatine in OCD: effects on the motivational aspects and dysregulated circadian rhythms

Introduction: A considerable proportion of subjects with obsessive-compulsive disorder (OCD) have shown resistance or an incomplete response to the standard first-line treatment of serotonin reuptake inhibitors. In particular, patients often continue to show disrupted circadian rhythms with related sleep disturbances and comorbidity with bipolar spectrum disorders.

Areas covered: This paper discusses the possible role of agomelatine in the treatment of motivational aspects and dysregulated circadian rhythms of OCD. In particular, the article highlights the pharmacokinetics and pharmacodynamics of agomelatine. Additionally, the article highlights its clinical efficacy, safety and tolerability and provides perspectives on its future development as a potential therapy for the treatment of OCD.

Expert opinion: Agomelatine offers the effective resynchronization of circadian rhythm with an improvement in patients’ reward mechanism, incentive motivation and general OCD symptoms. Indeed, the authors believe that agomelatine could be a valid alternative drug in treatment-resistant OCD patients, particularly those suffering with bipolar spectrum comorbidity and related sleep disturbances.     

Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

Differing effects of prosaccades and antisaccades on postural stability

The goal of the study was to examine the effect of different types of eye movements on postural stability. Ten healthy young adults (25 ± 3 years) participated in the study. Postural control was measured by the TechnoConcept© platform and recorded in Standard Romberg and Tandem Romberg conditions while participants performed five oculomotor tasks: two fixation tasks (central fixation cross, without and with distractors), two prosaccade tasks toward peripheral targets displayed 4° to the left or to the right of the fixation cross (reactive saccades induced by a gap 0 ms paradigm and voluntary saccades induced by an overlap 600 ms paradigm) and one antisaccade task (voluntary saccade made in the opposite direction of the visual target). The surface, the length, and the mean speed of the center of pressure were analyzed. We found that saccadic eye movements improved postural stability with respect to the fixation tasks. Furthermore, antisaccades were found to decrease postural stability compared to prosaccades (reactive as well as voluntary saccades). This result is in line with the U-shaped nonlinear model described by Lacour et al. (Neurophysiol Clin 38:411–421, 2008), showing that a secondary task performed during a postural task could increase (prosaccade task) or decrease (antisacade task) postural stability depending on its complexity. We suggest that the different degree of attentional resources needed for performing prosaccade or antisaccade tasks are, most likely, responsible for the different effect on postural control.     

Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization

Bacteria causing infections in hospitalized patients are increasingly antibiotic resistant. Classical infection control practices are only partially effective at preventing spread of antibiotic-resistant bacteria within hospitals. Because the density of intestinal colonization by the highly antibiotic-resistant bacterium vancomycin-resistant Enterococcus (VRE) can exceed 10⁹ organisms per gram of feces, even optimally implemented hygiene protocols often fail. Decreasing the density of intestinal colonization, therefore, represents an important approach to limit VRE transmission. We demonstrate that reintroduction of a diverse intestinal microbiota to densely VRE-colonized mice eliminates VRE from the intestinal tract. While oxygen-tolerant members of the microbiota are ineffective at eliminating VRE, administration of obligate anaerobic commensal bacteria to mice results in a billionfold reduction in the density of intestinal VRE colonization. 16S rRNA gene sequence analysis of intestinal bacterial populations isolated from mice that cleared VRE following microbiota reconstitution revealed that recolonization with a microbiota that contains Barnesiella correlates with VRE elimination. Characterization of the fecal microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation demonstrated that intestinal colonization with Barnesiella confers resistance to intestinal domination and bloodstream infection with VRE. Our studies indicate that obligate anaerobic bacteria belonging to the Barnesiella genus enable clearance of intestinal VRE colonization and may provide novel approaches to prevent the spread of highly antibiotic-resistant bacteria.     

Dimensional changes following alveolar ridge preservation in the posterior area using bovine-derived xenografts and collagen membrane compared to spontaneous healing: a 6-month randomized controlled clinical trial

Clinical Oral Investigations - To assess dimensional changes following alveolar ridge preservation using bovine-derived xenograft with 10% collagen and collagen membrane compared to ridge...