An evaluation of sealing ability of endodontic materials as root canal sealers

An in vitro dye leakage study was carried out to compare the apical microleakage of vitapex (calcium hydroxide based paste) when used with single gutta percha cone with that of dentalis KEZ (calcium hydroxide and zincoxide eugenol based sealer) and zincoxide-eugenol sealer when used with laterally condensed gutta percha obturation technique. One hundred single rooted human anterior teeth were instrumented and randomly divided into three experimental groups of 30 teeth each and two control groups of 5 teeth each. Teeth in the first group were obturated using a single master gutta percha cone and vitapex as root canal sealer and those of second group were obturated with laterally condensed gutta percha using dentalis KEZ as sealer. Third experimental group was filled with laterally condensed gutta-percha using zinc-oxide eugenol as sealer. Teeth were then suspended in 2% methylene blue. After this, teeth were demineralized dehydrated and cleared. Linear dye penetration was determined under stereomicroscope (x10) with calibrated eye piece. Results of this study showed that calcium hydroxide based endodontic material leaked comparatively less as compared to zinc oxide Eugenol sealer. Vitapex with single gutta-percha cone provided an adequate apical Seal against dye penetration.     

Post Roux-en-Y gastric bypass complications: A comparative study assessing the clinical effectiveness of oesophagogastroduodenoscopy and oral-contrast swallow

Introduction

Anastomotic strictures at the gastrojejunal anastomosis have been reported to occur in 3–20% of patients following a Roux-en-Y gastric bypass (RYGB). Patients commonly present with dysphagia, vomiting and post-prandial pain. Clearly using the appropriate investigations to diagnose the potential complications have both clinical and economical benefits. The reported study compared whether Oesophagogastroduodenoscopy (OGD) or oral-contrast swallow should be employed in patient presenting with post-operative complications following RYGB.

Association of absolute lymphocyte count and peripheral blood lymphocyte subsets percentage with minimal residual disease at the end of induction in pediatric B cell acute lymphoblastic leukemia

Absolute lymphocyte count (ALC) has been associated with overall survival (OS) and event-free survival, but we do not know if ALC is associated with minimal residual disease (MRD) at the end of induction (EOI) and whether it can be used as surrogate marker in resource limited settings. Immunological differences between MRD-positive and MRD-negative B ALL patients at the EOI are not known at present. This prospective study evaluated the association of ALC and peripheral blood lymphocyte subset percentage at the EOI with MRD. ALC was done at baseline, day 8, and day 15 and at EOI. Assessment for MRD and peripheral blood lymphocyte subset was done at EOI. In 2-year study duration, 197 B cell acute lymphoblastic leukemia (ALL) patients were recruited out of which 150 were analyzed. Peripheral lymphocyte subset percentage was available for 58 patients. We found that ALC at baseline, day 8, day 15, and EOI was not associated with MRD. Day 8 ALC was significantly higher in poor steroid responders (day 8 blasts?>?1?×?10⁹ cells/l) (p?<?0.0001). At the EOI, CD4^?CD8⁺ cell percentage in peripheral blood were significantly higher in MRD-positive patients than MRD-negative patients (p?=?0.01). Our study suggests that ALC at any point is not a surrogate marker for MRD. Immunologically MRD-positive and MRD-negative patients differ in CD4^?CD8⁺ cells. The role of CD8⁺T and TCRαβCD3⁺T cells in eliminating residual leukemic cells need to be studied further by functional assays.     

Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia.

OBJECTIVE: To determine the mechanism leading to striatal dopamine (DA) loss in dopa-responsive dystonia (DRD). BACKGROUND: Although mutations in the gene GCH1, coding for the tetrahydrobiopterin (BH4) biosynthetic enzyme guanosine triphosphate-cyclohydrolase I, have been identified in some patients with DRD, the actual status of brain BH4 (the cofactor for tyrosine hydroxylase [TH]) is unknown. METHODS: The authors sequenced GCH1 and measured levels of total biopterin (BP) and total neopterin (NP), TH, and dopa decarboxylase (DDC) proteins, and the DA and vesicular monoamine transporters (DAT, VMAT2) in autopsied brain of two patients with typical DRD. RESULTS: Patient 1 had two GCH1 mutations but Patient 2 had no mutation in the coding region of this gene. Striatal BP levels were markedly reduced (<20% of control subjects) in both patients and were also low in two conditions characterized by degeneration of nigrostriatal DA neurons (PD and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated primate), whereas brain NP concentrations were selectively decreased (<45%) in the DRD patients. In the putamen, both DRD patients had severely reduced (<3%) TH protein levels but had normal concentrations of DDC protein, DAT, and VMAT2. CONCLUSIONS: The data suggest that 1) brain BH4 is decreased substantially in dopa-responsive dystonia, 2) dopa-responsive dystonia can be distinguished from degenerative nigrostriatal dopamine deficiency disorders by the presence of reduced brain neopterin, and 3) the striatal dopamine reduction in dopa-responsive dystonia is caused by decreased TH activity due to low cofactor concentration and to actual loss of TH protein. This reduction of TH protein, which might be explained by reduced enzyme stability/expression consequent to congenital BH4 deficiency, can be expected to limit the efficacy of acute BH4 administration on dopamine biosynthesis in dopa-responsive dystonia.     

SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan

Neurodegeneration is a complex neurological phenomenon characterized by disturbed coherence in neuronal efflux. Progressive neuronal loss and brain damage due to various age-related pathological hallmarks perturb the behavioral balance and quality of life. Sirtuins have been widely investigated for their neuroprotective role, with SIRT1 being the most contemplated member of the family. SIRT1 exhibits significant capabilities to enhance neurogenesis and cellular lifespan by regulating various pathways, which makes it an exciting therapeutic target to inhibit neurodegenerative disease progression. SIRT1 mediated neuronal fortification involves modulation of molecular co-factors and biochemical pathways responsible for the induction and sustenance of pro-inflammatory and pro-oxidative environment in the cellular milieu. In this review, we present the major role played by SIRT1 in maintaining cellular strength through the regulation of genomic stability, neuronal growth, energy metabolism, oxidative stress, inhibiting mechanisms and anti-inflammatory responses. The therapeutic significance of SIRT1 has been put into perspective through a comprehensive discussion about its ameliorating potential against neurodegenerative stimuli in a variety of diseases that characteristically impair cognition, memory and motor coordination. This review enhances the acquaintance concerned with the neuroprotective potential of SIRT1 and thus promotes the development of novel SIRT1 regulating therapeutic agents and strategies.     

Process, rationale, and interventions of Pakistan's National Action Plan on Chronic Diseases

Most developing countries do not comprehensively address chronic diseases as part of their health agendas because of lack of resources, limited capacity within the health system, and the threat that the institution of national-level programs will weaken local health systems and compete with other health issues. An integrated partnership-based approach, however, could obviate some of these obstacles. In Pakistan, a tripartite public-private partnership was developed among the Ministry of Health, the nongovernmental organization (NGO) Heartfile, and World Health Organization. This was the first time an NGO participated in a national health program; NGOs typically assume a contractual role. The partnership developed a national integrated plan for health promotion and the prevention and control of noncommunicable diseases (NCDs), which as of January 2006 is in the first stage of implementation. This plan, called the National Action Plan on NCD Prevention, Control, and Health Promotion (NAP-NCD), was released on May 12, 2004, and attempts to obviate the challenges associated with addressing chronic diseases in countries with limited resources. By developing an integrated approach to chronic diseases at several levels, capitalizing on the strengths of partnerships, building on existing efforts, and focusing primary health care on chronic disease prevention, the NAP-NCD aims to mitigate the effects of national-level programs on local resources. The impact of the NAP-NCD on population outcomes can only be assessed over time. However, this article details the plan's process, its perceived merits, and its limitations in addition to discussing challenges with its implementation, highlighting the value of such partnerships in facilitating the missions and mandates of participating agencies, and suggesting options for generalizability.     

Transforming growth factor-ß suppresses metastasis in a subset of human colon carcinoma cells

ABSTRACT: BACKGROUND: TGFbeta signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFbeta signaling. METHODS: To test the importance of TGFbeta signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFbeta response (FET), or tumorigenic with TGFbeta response (FETalpha) or tumorigenic with abrogated TGFbeta response via introduction of dominant negative TGFbetaRII (FETalpha/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. RESULTS: Abrogation of TGFbeta signaling through introduction of a dominant negative TGFbeta receptor II (TGFbetaRII) in non-metastatic in FETalpha human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFbeta signaling in FETalpha-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFbeta signaling is a metastasis suppressor, we rescued TGFbeta signaling in CBS metastatic colon cancer cells that had lost TGFbeta receptor expression due to epigenetic repression. Restoration of TGFbeta signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFbeta signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. CONCLUSIONS: The observations presented here indicate a metastasis suppressor role for TGFbeta signaling in human colon cancer cells. This raises the concern that therapies targeting inhibition of TGFbeta signaling may be imprudent in some patient populations with residual TGFbeta tumor suppressor activity.     

Should the chickenpox vaccine be included in the National Immunization Schedule in India?

Varicella (chickenpox) is an acute, highly contagious viral disease with worldwide distribution. The highest prevalence occurs in the 4-10 year age group but tends to be more severe in adults. It may be fatal in neonates, immunocompromised persons, and normal adults, especially smokers. Varicella is usually a benign childhood disease, and rarely rated as an important public health problem, but this can be severe and even fatal in otherwise healthy children (< 1 out of every 10,000 cases). Chickenpox can cause pneumonia (23 out of every 10,000 cases), and is an important risk factor for developing severe invasive "strep" (group A streptococcal disease). Complications of varicella include bacterial infections (up to 5% of cases), decreased platelets, arthritis, hepatitis, pneumonia (more commonly in adults) or encephalitis (1 in 10,000 cases), which may cause a failure of muscular coordination, sometimes resulting in persistent sequelae or death. Varicella is the leading cause of vaccine-preventable death in children. Universal vaccination can cause a dramatic reduction in the incidence of varicella, associated complications, hospitalizations and fatality rates. In India, due to the high cost of the vaccine, it would be difficult to vaccinate a large percentage of the children. The government of India should consider the inclusion of varicella vaccine in the National Immunization Schedule with the help of International agencies.