Multipotent adult progenitor cell‐loaded demineralized bone matrix for bone tissue engineering

Multipotent adult progenitor cells (MAPCs) from bone marrow have been shown to be capable of forming bone, cartilage and other connective tissues. In addition, MAPCs differentiate into lineages that are different from their germ layers of origin. Previous studies showed the ability of MAPCs to improve cardiac function and control allogenic‐reactive responses associated with acute graft versus host disease. In the current study, we evaluated the ability of MAPCs to produce bone matrix on demineralized bone allograft substrates. Specifically, MAPCs expressed alkaline phosphatase, produced extracellular matrix proteins and deposited calcium‐containing mineral on demineralized bone matrices. Furthermore, the addition of MAPCs on demineralized bone matrix (DBM) scaffolds enhanced osteoinductivity of the carrier in a rat ectopic pouch model. These results demonstrated the potential of MAPCs as a new approach for bone repair in tissue‐engineering applications. Copyright © 2013 John Wiley & Sons, Ltd.     

The platinum (II) complex [Pt(O,O′-acac)(γ-acac)(DMS)] alters the intracellular calcium homeostasis in MCF-7 breast cancer cells

It was previously demonstrated that [Pt(O,O′-acac)(γ-acac)(DMS)] exerted toxic effects at high doses, whilst sub-cytotoxic concentrations induced anoikis and decreased cell migration. Aim of this study was to investigate the hypothesis that [Pt(O,O′-acac)(γ-acac)(DMS)] alters the [Ca²⁺]_i and that this is linked to its ability to trigger rapid apoptosis in MCF-7 cells. Thus, cells were treated with [Pt(O,O′-acac)(γ-acac)(DMS)] and its effects on some of the systems regulating Ca²⁺ homeostasis were studied, also in cells dealing with the complex changes occurring during the Ca²⁺ signalling evoked by extracellular stimuli. [Pt(O,O′-acac)(γ-acac)(DMS)] caused the decrease of PMCA activity (but not SERCA or SPCA) and Ca²⁺ membrane permeability. These two opposite effects on [Ca²⁺]_i resulted in its overall increase from 102 ± 12 nM to 250 ± 24 nM after 15 min incubation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] were also evident when cells were stimulated with ATP: the changes in Ca²⁺ levels caused by purinergic stimulation resulted altered due to decreased PMCA activity and to the closure of Ca²⁺ channels opened by purinergic receptor. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not affect the store-operated Ca²⁺ channels opened by thapsigargin or by ATP. [Pt(O,O′-acac)(γ-acac)(DMS)] provoked the activation of PKC-α and the production of ROS that were responsible for the Ca²⁺ permeability and PMCA activity decrease, respectively. The overall effect of [Pt(O,O′-acac)(γ-acac)(DMS)] is to increase the [Ca²⁺]_i, an effect that is likely to be linked to its ability to trigger rapid apoptosis in MCF-7 cells. These data reinforce the notion that [Pt(O,O′-acac)(γ-acac)(DMS)] would be a promising drug in cancer treatment.     

A method for managing re-identification risk from small geographic areas in Canada

Background  

A common disclosure control practice for health datasets is to identify small geographic areas and either suppress records from these small areas or aggregate them into larger ones. A recent study provided a method for deciding when an area is too small based on the uniqueness criterion. The uniqueness criterion stipulates that an the area is no longer too small when the proportion of unique individuals on the relevant variables (the quasi-identifiers) approaches zero. However, using a uniqueness value of zero is quite a stringent threshold, and is only suitable when the risks from data disclosure are quite high. Other uniqueness thresholds that have been proposed for health data are 5% and 20%.     

A randomized, double-blind, placebo-controlled study of sibutramine in the treatment of binge-eating disorder

BACKGROUND: Although antidepressants are the pharmacological agents most often studied in the treatment of binge-eating disorder (BED), preliminary evidence from an open trial suggests that the antiobesity agent sibutramine hydrochloride may be effective. The objective of this study was to evaluate the efficacy and tolerability of sibutramine in obese patients with BED. METHODS: After a 2-week run-in period, 60 obese outpatients (body mass index [calculated as weight in kilograms divided by the square of height in meters] 30-45), who met DSM-IV criteria for BED were randomly assigned to receive sibutramine hydrochloride (n = 30), 15 mg/d, or placebo (n = 30) in a 12-week double-blind study at 2 centers. The primary outcome measure was binge frequency, expressed as the number of days with binge-eating episodes during the past week. Secondary outcome measures included Binge Eating Scale, Beck Depression Inventory scores, weight, and treatment responder status (remission and response). For each efficacy outcome, an intent-to-treat analysis was performed using random regression methods. RESULTS: There was a significant reduction in the number of days with binge episodes in the sibutramine group compared with the placebo group (t203 = 2.14; P =.03); this was associated with an important and significant weight loss (-7.4 kg) compared with a small weight gain in the placebo group (1.4 kg) (t147 = 4.88; P<.001). Sibutramine was also associated with a significantly greater rate of reduction in Binge Eating Scale (t202 = 3.64; P<.001) and Beck Depression Inventory (t201 = 3.72; P<.001) scores. Dry mouth (P =.01) and constipation (P<.001) were more common adverse reactions with sibutramine than placebo. CONCLUSIONS: Sibutramine is effective and well tolerated in the treatment of obese patients with BED. Its effects address 3 main domains of the BED syndrome, ie, binge eating, weight, and related depressive symptoms.     

Possible immunomodulatory actions of Carica papaya seed extract

Carica papaya seed extract is currently being marketed as a nutritional supplement with purported ability "to rejuvenate the body condition and to increase energy". The product claims to improve immunity against common infection and body functioning. The present study was initiated to analyze the chemical constituents of the Carica Seed Extract and determine the potential immunomodulatory properties of the different bioactive fractions. These immunomodulatory activities of crude Carica Seed Extract and its bioactive fractions were examined in vitro using lymphocyte proliferation assays and complement-mediated hemolytic assay. Three major observations were made in this study: (1) the crude Carica Seed Extract and two other bioactive fractions significantly enhanced the phytohemagglutinin responsiveness of lymphocytes; (2) none of the Carica Seed Extract (at the concentrations used in this study) was able to protect the lymphocytes from the toxic effects of chromium; and (3) some of the bioactive fractions of Carica Seed Extract were able to significantly inhibit the classical complement-mediated hemolytic pathway. These findings provide evidence for immunostimulatory and anti-inflammatory actions of Carica Seed Extract. No single compound is likely responsible for these activities. Further purification, isolation and characterization of the active components are needed.     

Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum

The irreversible loss of the dopamine-mediated control of striatal function is considered the functional substrate of the motor symptoms of Parkinson's disease. This pathological event causes a complex rearrangement of neuronal activity which involves specific dopamine-regulated cellular functions and, secondarily, several other cellular properties and transmitter systems. In the present study, we applied recently developed cDNA microarray technology to investigate the genetic correlates of the alterations produced by 6-hydroxydopamine-induced dopamine denervation in the nucleus striatum. We found that chronic dopamine denervation caused the modulation of 50 different genes involved in several cellular functions. In particular, products of the genes modulated by this experimental manipulation are involved both in the intracellular transduction of dopamine signal and in the regulation of glutamate transmission in striatal neurons, providing some information on the possible neuronal events which lead to the reorganization of glutamate transmission in the striatum of parkinsonian rats.