Improving overall health of children living with HIV through an oral health intervention in Cambodia: study protocol for a randomized controlled trial.

BACKGROUND: Currently, the number of children living with HIV is the highest ever. This has led to an increased focus on a healthy life expectancy in this population. Improving oral health status may contribute to improved immunity, which could in turn lead to greater overall health in this population. This study aims to evaluate the effectiveness of an oral health intervention in improving oral health and immune status among children living with HIV in Cambodia. METHODS: A randomized controlled trial will be conducted in Phnom Penh from May 2018 to April 2020. Among 520 dyads of children living with their respective caregivers, half will be randomly allocated to the intervention group and the other half to the control group. Children aged 3-15 years who are currently receiving antiretroviral therapy at the National Pediatric Hospital will be recruited. In addition, 260 HIV-uninfected children (age-matched to the intervention group) will be recruited from the communities. They, together with their caregivers, will comprise the second control group. The main components of the intervention will include oral health education sessions for the children, as well as daily oral self-care under the supervision of their caregivers. The primary study outcome will be the change in oral health status including the number of decayed, missing, or filled permanent teeth, and the secondary outcome will be CD4 count. The effects of the intervention will be assessed by comparing outcome indicators between the children in the intervention and those in the control groups. DISCUSSION: This trial will investigate the effects of an oral health intervention on the improvement of oral health and immune status among children living with HIV and determine the differences compared with the control groups. This intervention would encourage the promotion of oral health interventions among children living with HIV and thus contribute to delaying the onset of AIDS. TRIAL REGISTRATION: Current Controlled Trials, International Standard Randomized Controlled Trial Number Register, ISRCTN15177479 . Registered on 17 January 2018.

Recovery of Pure Red Cell Aplasia Following Hematopoietic Stem Cell Transplantation Associated with Interleukin (IL)-6 Elevation Caused by Odontogenic Infection.

We herein report a case of long-lasting pure red cell aplasia (PRCA) after major ABO-incompatible allogeneic stem cell transplantation (SCT) for acute lymphoblastic leukemia. The patient needed red blood cell (RBC) transfusion every week after SCT. On day 236, he was diagnosed with odontogenic infection, and the serum levels of Interleukin (IL)-6 were elevated to 12.1 pg/mL. After that, the numbers of reticulocyte rapidly began to increase, and RBC support was not needed from day 251. No standard care for PRCA following SCT has been established. The IL-6 elevation caused by the odontogenic infection therefore appears to have been affected by the improvement in PRCA.

Root Cause Analysis: An Examination of Odontogenic Origins of Acute Maxillary Sinusitis in Both Immunocompetent & Immunocompromised Patients.

BACKGROUND AND PURPOSE: Dental and periodontal diseases represent important but often overlooked causes of acute sinusitis. Our goal was to examine the prevalence of potential odontogenic sources of acute maxillary sinusitis according to immune status and their associations with sinusitis. MATERIALS AND METHODS: A retrospective review of maxillofacial computed tomography studies from 2013 to 2014 was performed. Each maxillary sinus and its ipsilateral dentition were evaluated for findings of acute sinusitis and dental/periodontal disease. RESULTS: Eighty-four patients (24 immunocompetent, 60 immunocompromised) had 171 maxillary sinuses that met inclusion criteria for acute maxillary sinusitis. Inspection of dentition revealed oroantral fistula in 1%, periapical lucencies in 16%, and projecting tooth root(s) in 71% of cases. Immunocompromised patients were more likely to have bilateral sinusitis than immunocompetent patients (67% vs 33%, P = 0.005). A paired case-control analysis in a subset of patients with unilateral maxillary sinusitis (n = 39) showed a higher prevalence of periapical lucency in association with sinuses that had an air fluid level-29% of sinuses with a fluid level had periapical lucency compared with 12% without sinus fluid (P = 0.033). CONCLUSIONS: Potential odontogenic sources of acute maxillary sinusitis are highly prevalent in both immunocompetent and immunocompromised patients, although the 2 patient populations demonstrate no difference in the prevalence of these potential odontogenic sources. Periapical lucencies were found to be associated with an ipsilateral sinus fluid level. Increased awareness of the importance of dental and periodontal diseases as key components of maxillofacial computed tomography interpretation would facilitate a more appropriate and timely treatment.

Comparative evaluation of pro-inflammatory cytokine levels in pulpotomized primary molars.

The present in vivo study was performed to investigate the levels of the pro-inflammatory cytokines, interleukin (IL)-1α, IL-6, and IL-8, in primary molars for which pulpotomy was clinically indicated, and to evaluate the success rates of three different pulpotomy agents employed for cariously (CExp) or mechanically exposed (MExp) primary molars. Forty-seven primary molars were classified as MExp or CExp according to the type of pulpal exposure. Pulp tissue was harvested and analyzed using enzyme-linked immunosorbent assay (ELISA). Subsequently, three pulpotomy agents-calcium hydroxide (CH), mineral trioxide aggregate (MTA), and formocresol (FC)-were applied randomly, and the outcome was observed radiographically for 18 months. Levels of IL-6 and IL-8 were significantly higher in CExp pulp than in MExp pulp (P < 0.05). In the CH pulpotomy group, MExp teeth showed a higher success rate than CExp teeth. There was no significant difference in success rate between MExp and CExp teeth in both the FC and MTA groups. The levels of IL-6 and IL-8 have the potential to become indicators of pulp status and can be monitored by researchers to make the prognosis of vital pulp therapies less uncertain. As MTA and FC yielded higher rates of success than CH in CExp teeth, the choice of pulpotomy agent appears to be important in this context.

Exploring the relationship between childhood adversity and oral health: An anecdotal approach and integrative view.

During the past two decades, increasing recognition has been given to a relationship between oral health and systemic diseases. Associated systemic conditions include cardiovascular disease, diabetes, low birth weight and preterm births, respiratory diseases, rheumatoid arthritis, obesity, osteoporosis, and, in particular among oral conditions, periodontal disease. Low-grade inflammation is a common denominator linking these disorders. Applying an anecdotal approach and an integrative view, the medical and dental histories of two women document increasing ill health subsequent to incidences of maltreatment and sexual abuse, including oral penetration, at an early age. Comprehensive oral rehabilitation was required in both cases. These cases open for medical insight with regard to their implicit patho-physiology, when integrated with current evidence from neuroscience, endocrinology, and immunology, converging in the concepts of allostasis and allostatic load. In cases such as those presented in this paper, primary care physicians (family doctors, General Practitioners) and dentists may be the first to identify an etiological pattern. This report underlines the importance of increased and enhanced multidisciplinary research cooperation among health professionals. Our hypothesis is that childhood adversity may affect all aspects of human health, including adult oral health.

A review of pathogenesis, diagnosis, treatment options, and differential diagnosis of odontogenic infections: a rather mundane pathology?

Odontogenic infections are common in the dental practice and their treatment should be a standard procedure for every dentist. For optimal management of septic intraoral problems, the practitioner must understand the underlying causes and etiologies of odontogenic infections. Therefore, the purpose of this article is to outline basic inflammatory processes involved in the development of odontogenic and intraoral infections including relevant pathogens, biochemical processes mediated by pro-inflammatory molecules, the basics of abscess formation, the host response, and the clinical appearance of intraoral septic processes. Furthermore, treatment modalities of odontogenic infections and associated lesions are discussed and a brief explanation of possible complications and their management is provided.

Oral manifestations of primary immune deficiencies in children.

An important task for both dentists and pediatricians dealing with patients manifesting different oral lesions is to be able to differentiate changes signaling systemic disease from those appearing without any concomitant serious health problem. In this article, symptomatology of selected primary immune deficiency diseases are discussed with particular emphasis on oral manifestations reported in this group of disorders. Facial, dental, and oral findings compose a constellation of symptoms observed in immunodeficiency diseases. Predisposition to bacterial invasion, cytokine dysregulation, tissue inflammatory process, and necrosis lead to early-onset oral lesions and periodontitis. Developmental abnormalities, periodontal disease, and oral lesions may accompany immunodeficiency and require particular awareness directed toward diagnosis of an underlying disease of the immune system.

Odontoblasts in the dental pulp immune response.

Recent studies have demonstrated that human dental pulp cells sense pathogens and elicit innate and/or adaptive immunity. Particular attention has been paid to odontoblasts that are situated at the pulp-dentin interface and constitute the first line of defense to cariogenic bacteria entering dentin after enamel disruption. In this review, recent in vitro and in vivo data suggesting that odontoblasts initiate immune/inflammatory events within the dental pulp in response to cariogenic bacteria are discussed. These data include sensing of pathogens by Toll-like receptors (TLRs), production of chemokines upon cell stimulation with microbial by-products and induction of dendritic cell migration. Additional results presented here reveal that all TLR genes are expressed in the healthy human dental pulp that is thus well equipped to combat pathogens entering the tissue. Seventeen chemokine genes including CXCL12, CCL2, CXCL9, CX3CL1, CCL8, CXCL10, CCL16, CCL5, CXCL2, CCL4, CXCL11 and CCL3, and 9 chemokine receptor genes including CXCR4, CCR1, CCR5, CX3CR1, CCR10 and CXCR3, are also expressed in pulp. TLR2, CCL2 and CXCL1 are upregulated in odontoblasts both under caries lesions and upon stimulation with pathogen by-products. These molecules thus appear as preferential targets for the design of therapeutic agents able to reduce the immune/inflammatory response to cariogenic bacteria and favor pulp healing.

Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations.

Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated serum IgE, and a variety of connective tissue and skeletal abnormalities. Individuals with HIES share a characteristic facial appearance and many oral manifestations including retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis. Mutations in STAT3 account for the majority, if not all, of the cases of autosomal dominant HIES, but the pathogenesis of the many varied features remains poorly understood. In this review, we discuss the clinical phenotype of HIES including immunologic and non-immunologic features, the genetics of HIES, and treatment.

Characterization of mechanical properties of transgenic tobacco roots expressing a recombinant monoclonal antibody against tooth decay.

In this article, we describe a new approach that allows the determination of the magnitude of force required to break single plant roots. Roots were taken from transgenic tobacco plants, expressing a secreted monoclonal antibody. They were divided into four key developmental stages. A novel micromanipulation technique was used to pull to breakage, single tobacco roots in buffer in order to determine their breaking force. A characteristic uniform step-wise increase in the force up to a peak force for breakage was observed. The mean breaking force and mean work done were 101mN and 97microJ per root respectively. However, there was a significant increase in breaking force from the youngest white roots to the oldest, dark red-brown roots. We speculate that this was due to increasing lignin deposition with root stage of development (shown by phloroglucinol staining). No significant differences between fresh root mass, original root length, or mean root diameter for any of the root categories were found, displaying their uniformity, which would be beneficial for bioprocessing. In addition, no significant difference in antibody yield from the different root categories was found. These data show that it is possible to characterise the force requirements for root breakage and should assist in the optimisation of recombinant protein extraction from these roots.

Dentistry and Ayurveda--III (basics-ama, immunity, ojas, rasas, etiopathogenesis and prevention).

This article of the series Dentistry and Ayurveda describes in brief, the basic principles and unique concepts involved in Ayurveda namely the concepts of Ama, Ojas, Rasas (tastes-types and the factors affecting the choice of the drug/medicine etc.), immunity, etiopathogenesis and prevention of diseases in Ayurveda in general.

Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses.

AIM: To investigate in individuals with symptomatic dental abscesses the occurrence of functional polymorphisms within five genes involved with the immune response. The functional gene polymorphisms analysed were CD14 (-260 C/T), IL1B (+3954 C/T), IL6 (-174 G/C,), IL10 (-1082 G/A) and TNFA (-308 G/A). METHODOLOGY: Genomic DNA obtained from oral swabs from individuals with symptomatic dental abscesses and asymptomatic inflammatory periapical lesions, without previous exacerbation, was submitted to restriction fragment length polymorphism (RFLP) analyses to determine each individual genotype. The chi-square and principal components analysis tests were used for statistical analysis. RESULTS: A significant association was observed between the occurrence of the GG genotype or the G allele expression of the polymorphic locus-174 (G/C) of the IL6 gene, and the presence of the symptomatic dental abscesses in women and in individuals < or =35 years old. The principal components analysis suggested predominance of the symptomatic dental abscesses in individuals displaying: high-producer IL6 genotype; intermediate and high-producer IL1B genotypes and low-producer TNFA genotype. CONCLUSIONS: The present study suggests that genetic factors are associated with susceptibility to develop symptomatic dental abscesses.

Correlation between phenotypic characteristics of mononuclear cells isolated from human periapical lesions and their in vitro production of Th1 and Th2 cytokines.

UNLABELLED: The development and progression of periapical dental lesions, mediated by the specific immune response, are poorly understood. In these processes, an interplay of different proinflammatory and immunoregulatory cytokines is of crucial importance. OBJECTIVES: To examine the activation of T helper 1 (Th1) and Th2 immune responses in 25 human periapical lesions based on the ex vivo production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by mononuclear cells (PL-MNC). METHODS: The levels of IFN-gamma and IL-4 in culture supernatants of PL-MNC, determined by ELISA, were correlated with concentrations of these cytokines in cultures of control MNC from peripheral blood (PB-MNC), cellular composition of inflammatory cells and phenotypic characteristics of PL-MNC. RESULTS: We detected high levels of IFN-gamma in all samples, after cell stimulation with phorbol myristate acetate and Ca(2+) ionophore, that were not statistically different from the levels of IFN-gamma in PB-MNC cultures. IL-4 was detected in 76% samples, but its concentrations were much lower than in PB-MNC samples. The levels of IFN-gamma were higher in cultures of PL-MNC isolated from periapical lesions with predominance of T cells (T-type lesions) and correlated positively with the proportion of antigen-presenting cells (macrophages and dendritic cells), CD4(+) T cells and IgG2(+) B cells/plasma cells. The levels of IL-4 correlated negatively with the proportion of macrophages, but positively with the number of mast cells and IgG4(+) cells. IL-18Ralpha, a stable marker of Th1 cells, was detected on a relatively small proportion of CD3(+) T cells and its expression correlated with the levels of IFN-gamma. However, the expression of ST2L, a stable Th2 cell marker, was not detected. The levels of Th1 and Th2 cytokines did not correlate with clinical characteristics of the lesions, defined by the presence of symptoms. CONCLUSION: Cumulatively, our results suggest the predominance of Th1 immune response in periapical lesions.

Oral and dental aspects of Sjögren's syndrome.

Sjögren's syndrome is a common condition which can result in significant physical and emotional debility. Dentists can play a pivotal role in the prompt diagnosis, investigation and management of patients with Sjögren's syndrome. A sound understanding of the pathogenesis, presentation and current management of Sjögren's syndrome, will enable the general dental practitioner to make a significant contribution to the oral health and general well-being of those affected by the disease. This article aims to provide the general dental practitioner with a comprehensive and practical guide to current developments and best practise in the care of these individuals.

The level of secretory IgA in saliva of patients with dental infections.

In this study the level of s-IgA in saliva of the patients with dental infections was measured. In the treatment only herbal drug was applied locally after the surgical procedures. The samples of saliva were taken three times: I--before treatment, II--after 3-4 days of the treatment and III--after the treatment. The level of s-IgA in saliva was measured according to ELISA method. Results were compared with 30-people control. Statistical analysis was done according to t-Student test. The level of s-IgA in saliva differed a lot between patients. Mean level of s-IgA in saliva of the patients was statistically higher before treatment and just after the treatment as compared to control (*p < 0.05, **p < 0.01). It was also shown that the level of s-IgA in women before treatment was higher as compared to man. The level of s-IgA was statistically higher in younger age group in comparison with older age group. The statistical differences between women treated and the control in measurements I and II were found (*p < 0.05; **p < 0.01).

[The monitoring of immunological indices in odontogenic abscesses and phlegmons and their differential diagnostic meaning]. / Monitoring immunologicheskikh pokazatelei pri odontogennykh abstsessakh i flegmonakh i ikh differentsial'no-diagnosticheskaia znachimost.

The immune homeostasis parameters have been monitored in 31 patients with odontogenic abscesses and phlegmons. Immunological values possessing differential diagnostic significance have been detected. Activation of phagocytosis, spontaneous and stimulated activity of phagocytes in parallel with a moderate decrease in the cellular functional reserve, increased immunoregulatory index, and moderate shifts in the concentrations of IgG and IgM are characteristic of odontogenic abscesses, while odontogenic phlegmons are characterized by deep depression of the phagocyte function and failure of cellular and humoral immunity. The disorders in the immune functions of patients with odontogenic phlegmons normalized 2 weeks later than in those with odontogenic abscesses. Both diseases run a wave-like course and are characterized by phasic changes in immunological parameters, which is significant for determining pathogenesis and choosing appropriate immunocorrective therapy.

[Dysregulation of the immunological mechanisms and phagocytic activity of the leukocytes--the leading cause of acute inflammation]. / Dizreguliatsiia immunologicheskikh mekhanizmov i fagotsitarnoi aktivnosti leikotsitov--vedushchaia prichina ostrogo vospaleniia.

The paper provides evidence for the assumption that the leading cause of acute odontogenic inflammatory processes of the face and neck is immunological deficiency which initiates the spread of infection from the radix dentis into cellular spaces. The type of inflammation (normo-, hyper-, or hypoergic) mainly depends upon the responsiveness of the phagocytic system. This conclusion is supported by the results of nonspecific and immunological correction made in patients.

Dental disease, caries related microflora and salivary IgA of children with severe congenital cardiac disease: an epidemiological and oral microbial survey.

The objectives were to determine levels of dental caries, plaque accumulation, gingival inflammation, knowledge of dental health practices, and oral bacterial loading of S. mutans, Lactobacillus sp., Candida sp., and salivary IgA in the mouths of children afflicted with severe congenital heart disease. A total of 60 children from the cardiac units of the Hospital for Sick Children and Guys Hospital Paediatric Department were compared with 60 case-matched control children from the Department of Orthodontics and Paediatric Dentistry, UMDS (Guys Dental School), London. Using the methodology of the World Health Organization, the decayed, missing and filled surfaces and teeth of primary (dmft) and permanent (DMFT) were compared. There were similar levels of caries in the cardiac (dmft 3.9 and DMFT 2.7) and the control (dmft 3.7 and DMFT 2.0). A significant difference was the proportion of untreated carious lesions in the cardiac group (52%) compared to the control group (32%; P < 0.001). Standard oral microbiological techniques were used to isolate S. mutans, Lactobacillus sp., Candida sp., and conventional methods for estimating salivary IgA. There was no difference between the cardiac and the control group. Children with severe congenital cardiac disease have moderately high levels of dental caries with a significantly greater amount of untreated disease. The high bacterial loading associated with high levels of bacterial dental plaque and gingivitis may put cardiac patients at unnecessary risk of developing bacterial endocarditis.