Evaluation of subcutaneous and alveolar implantation surgical sites in the study of the biological properties of root-end filling endodontic materials

Objective

The aim of this study was to compare two methodologies used in the evaluation of tissue response to root-end filling materials in rats.

Material and Methods

Forty rats were divided into 4 groups: in Groups I and II (control groups), empty polyethylene tubes were implanted in the extraction site and in the subcutaneous tissue, respectively; in Groups III and IV, polyethylene tubes filled with ProRoot MTA were implanted in the extraction site and in the subcutaneous tissue, respectively. The animals were killed 7 and 30 days after tube implantation, and the hemi-maxillas and the capsular subcutaneous tissue, both with the tubes, were removed. Specimens were processed and evaluated histomorphologicaly under light microscopy. The scores obtained were analyzed statistically by the Kruskal-Wallis test (p<0.05).

Results

There were no statistically significant differences between the implantation methods (p=0.78033, p=0.72039). It was observed that the 30-day groups presented a more mature healing process due to smaller number of inflammatory cells.

Conclusion

The present study showed no differences in tissue responses as far as the implantation site and the studied period were concerned. Alveolar socket implantation methodology represents an interesting method in the study of the biological properties of root-end filling endodontic materials due to the opportunity to evaluate bone tissue response.     

The quality of life of Palestinians living in chronic conflict: assessment and determinants

This study assessed the quality of life (QoL) of Palestinians living in conditions of chronic conflict and examined its determinants. An adapted World Health Organization quality of life (WHOQoL-Bref) instrument was used in a representative sample of 1,008 adults. Factor analysis and multiple regression were conducted to determine associations between demographic and socioeconomic characteristics and scores of extracted principal determinants, and estimated overall and domain-specific QoL scores. Men, older persons and those less educated reported lower QoL than their counterparts. Negative associations were also found with higher distress and fear levels, and lower financial and freedom status. The chronic and entrenched conflict over generations resulted in lower QoL for the population of the Occupied Palestinian Territory.

PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability

Mutations in the phosphatase and tensin homolog (PTEN) gene leading to PTEN protein deletion and subsequent activation of the PI3K/Akt signaling pathway are common in cancer. Here we show that PTEN inactivation in human T cell acute lymphoblastic leukemia (T-ALL) cells is not always synonymous with PTEN gene lesions and diminished protein expression. Samples taken from patients with T-ALL at the time of diagnosis very frequently showed constitutive hyperactivation of the PI3K/Akt pathway. In contrast to immortalized cell lines, most primary T-ALL cells did not harbor PTEN gene alterations, displayed normal PTEN mRNA levels, and expressed higher PTEN protein levels than normal T cell precursors. However, PTEN overexpression was associated with decreased PTEN lipid phosphatase activity, resulting from casein kinase 2 (CK2) overexpression and hyperactivation. In addition, T-ALL cells had constitutively high levels of ROS, which can also downmodulate PTEN activity. Accordingly, both CK2 inhibitors and ROS scavengers restored PTEN activity and impaired PI3K/Akt signaling in T-ALL cells. Strikingly, inhibition of PI3K and/or CK2 promoted T-ALL cell death without affecting normal T cell precursors. Overall, our data indicate that T-ALL cells inactivate PTEN mostly in a nondeletional, posttranslational manner. Pharmacological manipulation of these mechanisms may open new avenues for T-ALL treatment.     

Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization,safety and protection against challenge with Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected approximately two billion individuals worldwide with approximately 9.2 million new cases and 1.6 million deaths annually. Current efforts are focused on making better BCG priming vaccines designed to induce a comprehensive and balanced immunity followed by booster(s) targeting a specific set of relevant antigens in common with the BCG prime. We describe the generation and immunological characterization of recombinant BCG strains with properties associated with lysis of the endosome compartment and over-expression of key Mtb antigens. The endosome lysis strain, a derivative of BCG SSI-1331 (BCG₁₃₃₁) expresses a mutant form of perfringolysin O (PfoA_G137Q), a cytolysin normally secreted by Clostridium perfringens. Integration of the PfoA_G137Q gene into the BCG genome was accomplished using an allelic exchange plasmid to replace ureC with pfoA_G137Q under the control of the Ag85B promoter. The resultant BCG construct, designated AERAS-401 (BCG₁₃₃₁ ΔureC::ΩpfoA_G137Q) secreted biologically active Pfo, was well tolerated with a good safety profile in immunocompromised SCID mice. A second rBCG strain, designated AFRO-1, was generated by incorporating an expression plasmid encoding three mycobacterial antigens, Ag85A, Ag85B and TB10.4, into AERAS-401. Compared to the parental BCG strain, vaccination of mice and guinea pigs with AFRO-1 resulted in enhanced immune responses. Mice vaccinated with AFRO-1 and challenged with the hypervirulent Mtb strain HN878 also survived longer than mice vaccinated with the parental BCG. Thus, we have generated improved rBCG vaccine candidates that address many of the shortcomings of the currently licensed BCG vaccine strains.     

Clinical features of dystonia: a pathophysiological revisitation

PURPOSE OF REVIEW: To elucidate the pathophysiology of some clinical features of dystonic patients and to provide some new insight into the mechanisms underlying task-specific dystonia. RECENT FINDINGS: There are three general lines of work at the present time that may indicate the physiological substrate for dystonia. All three are persuasive and it is not clear whether they are related to each other or whether one is more important than the others. According to the first line of research, a loss of inhibition at different levels of the central nervous system might contribute for the excessive movement seen in dystonia. Another field of research suggests that dystonic patients may have faulty processing within the lemniscal pathway with abnormalities in the sensory-motor integration. Finally, another convincing line of evidence is that in some susceptible individuals, during the acquisition of new motor skills, the mechanisms of neuroplasticity are subtly abnormal. In the presence of such predisposition, several environmental factors, such as repetitive training or peripheral nervous system injury, can trigger an abnormal maladaptive plasticity, which can lead to an overt dystonia. SUMMARY: These findings may be relevant in the development of new therapeutic strategies in dystonia.     

Female-specific issues in multiple sclerosis

Complex neuroendocrine mechanisms regulating the immune response can be recognized in all autoimmune diseases. Such mechanisms develop through endocrine loops and feedback processes along the hypothalamus-pituitary-gonads axis and the hypothalamus-pituitary- adrenal gland axis. Females are not only more susceptible to autoimmune diseases, but are also more exposed to relevant variations of hormonal levels that physiologically go along with women's life. This paper reviews female-specific issues in multiple sclerosis and how treatments must be considered accordingly. In particular, aspects related to puberty, menses, fertility, pregnancy, lactation and menopause are considered in addition to epidemiological and clinical issues.