Adjunctive systemic antibiotic effect on periodontal state, salivary enzyme activity, and glycemia imbalance in type-2 diabetics after non-surgical periodontal management.

AIM: The current study aimed at analyzing the effect of non-surgical periodontal treatment accompanied by systemic antibiotics on salivary enzyme activities, periodontal parameters, and glycemic control in type-2 diabetic (T2D) patients with chronic periodontitis. METHODS: The study included 125 type-2 diabetic patients with chronic periodontitis who had good glycemic control (T2Dc), 125 type-2 diabetics who had bad glycemic control (T2Dpc). The 125 T2Dpc were divided randomly into two groups. The first one enrolled 63 T2Dpc and received a non-surgical periodontal treatment (T2Dpc + NST). The second group enrolled 62 T2Dpc and received the non-surgical treatment accompanied by systemic antibiotics (T2Dpc+NST+A). HbA1c, periodontal indices, and salivary enzyme activities were assessed for all groups. The Glycated hemoglobin (HbA1c) was assessed. The Salivary alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) activities were measured. RESULTS: The T2Dpc were characterized by the highest probing depth (PPD) and clinical attachment loss (CAL) periodontal scores, as well as ALP, AST, and ALT enzymatic activities. However, BOP did not differ significantly between T2Dc and T2Dpc. Whereas the rest of clinical parameters PI, GI, and OHI-S did not significantly differ between groups. The Pearson's analysis revealed three correlations between ALP-PPD, ALP-CAL, and ALP-BOP (bleeding on probing) in both T2Dc and T2Dpc (P < 0.05). Interestingly, a significant decrease in periodontal indices, salivary enzyme activities, and HbA1c was recorded in T2Dpc+NST+A group. CONCLUSION: The increase in ALP, AST, and ALT activities reflects the impact of uncontrolled T2D on periodontal tissue alteration. The ALP activity increase was associated with the severity of periodontal status in diabetic patients. In comparison to non-surgical treatment alone, the adjunct use of systemic antibiotics improves periodontal state, enzyme activity, and glycemic control.

Oral Healthcare Services Delivered During COVID-19 Lockdown: A Report from Eastern Mediterranean Region

ABSTRACT Objective: To describe oral healthcare services administered during the lockdown in the Eastern Mediterranean region and to investigate the role of socio-professional characteristics of dental practitioners or their self-reported COVID-19 infection. Material and Methods: A questionnaire was distributed to dental practitioners in all healthcare sectors in Jordan, Egypt, and Saudi Arabia. Results: There was a total of 335 participants, with the majority being females (N=225, 67.2%) and general practitioners (N=202, 60.3%). Cellulitis was the most common emergency encountered (N=108). The most common urgent procedures were for pulpitis, abscesses, and pericoronitis (N=191, 130, and 95, respectively). Country-specific significant associations were pulpitis in Egypt and Jordan, broken symptomatic teeth in Jordan, and biopsy in Egypt (p<0.05). The Ministry of Health was significantly associated with the management of dental infections, avulsion, and orthodontic emergencies, while university hospitals were significantly associated with advanced restorative procedures (p<0.05). Male practitioners performed significantly more procedures, particularly surgical emergencies (p<0.05). Conclusion: Dental infections were the most common complaints among dental patients during lockdown. Countryand sector-specific dental procedures are detected. Male gender seems to play a determinant role in performing a higher number of procedures, particularly for surgical emergencies (AU).

Long-term adverse events of three COVID-19 vaccines as reported by vaccinated physicians and dentists, a study from Jordan and Saudi Arabia.

Assessment of safety of COVID-19 vaccines is an ongoing process. This study aims to explore long-term adverse events reported by physicians and dentists who received at least two COVID-19 vaccine doses. A group of physicians and dentists were invited to complete a validated questionnaire that was composed of items on: socio-demographics, medical history, administered vaccines, and long-term adverse events (LTAE). Data of a total of 498 practitioners were included. Age ranged from 22 to 71 years (mean age= 35.75 ± 11.74) with a female majority (N = 348, 69.9%). The most frequently administered vaccines were Pfizer-BioNtech, Sinopharm and AstraZeneca vaccines. A total of 80 (16.0%) participants reported LTAEs which were mainly fatigue, menstrual disturbances, myalgia, arthralgia, dizziness, and headache (N = 32, 15, 8, 6, 4, and 4, respectively). There was no statistically significant association between LTAEs and: age, gender, or medical history (P > .05). The collective symptoms of fatigue, myalgia, arthralgia, dizziness, and headache were significantly associated with Sinopharm vaccine (P = .04). This was further confirmed by general linear multivariate model analysis. Less than 20% of COVID-19 vaccine recipients may complain of LTAEs that are mostly fatigue-related. It seems that factors such as age, gender, and medical status play a negligible role in development of these AEs. On the other hand, Sinopharm vaccine showed the highest significant association with these AEs followed by AstraZeneca vaccine.

Corrigendum: Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

[This corrects the article DOI: 10.3389/fendo.2018.00031.].

A characteristic signature of insulin-like growth factor (IGF) axis expression during osteogenic differentiation of human dental pulp cells (hDPCs): Potential co-ordinated regulation of IGF action.

The IGF axis is represented by two growth factors (IGF1 and IGF2), two cognate cell surface receptors (IGF1R and IGF2R), six soluble high affinity IGF binding proteins (IGFBP1-6) and several IGFBP proteases. IGF1 and IGF2 are present at high concentrations in bone and play a crucial role in the maintenance and differentiation of both foetal and adult skeleton. In order to understand the role of the IGF axis in bone and other tissues it is necessary to profile the expression and activity of all genes in the axis together with the activity of relevant ancillary proteins (including IGFBP proteases). In the current report we used differentiating human dental pulp cells (hDPC) to examine the expression and activity of the IGF axis during osteogenic differentiation of these cells. We found that, with the exception of IGF1 and IGFBP1, all components of the IGF axis are expressed in hDPCs. IGFBP-4 is the most abundantly expressed IGFBP species at both mRNA and protein levels under both basal and osteogenic conditions. Although we found no difference in IGFBP-4 expression under osteogenic conditions, we report increased expression and activity of pregnancy associated plasma protein-A (PAPP-A - an IGFBP-4 proteinase) leading to increased IGFBP-4 proteolysis in differentiating cell cultures. Further to this we report increased expression of IGF-2 (an activator of PAPP-A), and decreased expression of stanniocalcin-2 (STC2- a recently discovered inhibitor of PAPP-A) under osteogenic conditions. We also demonstrate that STC2 and PAPP-A are able to form complexes in hDPC conditioned medium indicating the potential for regulation of IGFBP-4 proteolysis through this mechanism. We suggest that these changes in the expression and activity of the IGF axis may represent part of an osteogenic signature characteristic of differentiating hDPCs.

Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

Oestrogen receptor ß (ERß) regulates osteogenic differentiation of human dental pulp cells.

Estradiol (E2) has many important actions in the tissues of the oral cavity. Disruption of E2 metabolism or alterations in systemic E2 concentrations have been associated with compromised periodontal health. In many instances such changes occur secondarily to the well characterised effects of E2 on bone physiology -especially maintenance of bone mineral density (BMD). Despite these important epidemiological findings, little is known about the mechanism of action of E2 in oral tissues or the expression and function of oestrogen receptor (ER) isoforms in these tissues. We have isolated human dental pulp cells (hDPCs), which are able to differentiate towards an osteogenic lineage under appropriate culture conditions. We show that hDPCs express ERα, ERß1, ERß2 and the cell membrane associated G protein-coupled ER (GPR30). Following osteogenic differentiation of hDPCs, ERß1 and ERß2 were up regulated approximately 50-fold while ERα and GPR30 were down regulated, but to a much lesser degree (approximately 2-fold). ERß was characterised as a 59kDa protein following Western blot analysis with validated antibodies and ERß was detected in both nuclear and cytoplasmic cell compartments following immunofluorescence (IF) and immunohistochemical (IHC) analysis of cultured cells. Furthermore isoform specific antibodies detected both ERß1 and ERß2 in DPC cultures and in situ analysis of ERß expression in decalcified tooth/pulp sections identified the odontoblast layer of pulp cells juxtaposed to the tooth enamel as strongly reactive for both ERß isoforms. Finally the use of isoform specific agonists identified ERß as the main receptor responsible for the pro-osteogenic effect of oestrogenic hormones in this tissue. Our data suggest that oestrogens stimulated osteogenic differentiation in hDPCs and that this action is mediated principally through the ERß isoform. These findings may have important consequences for the investigation and treatment of oral and periodontal pathologies which are associated with imbalances in oestrogen concentrations and action.

IGFBP-2 and -3 co-ordinately regulate IGF1 induced matrix mineralisation of differentiating human dental pulp cells.

Human dental pulp cells (DPCs), which are known to contain a subset of stem cells capable of reforming a dentin and pulp-like complex upon in vivo transplantation, were isolated from third molars of three healthy donors and differentiated to a matrix mineralisation phenotype using by culture in dexamethasone and l-ascorbic acid. qRT-PCR analysis of insulin-like growth factor ( IGF) axis gene expression indicated that all genes, except insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein-1 ( IGFBP-1), were expressed in DPCs. During differentiation upregulation of insulin-like growth factor binding protein-2 (IGFBP-2) and downregulation of insulin-like growth factor binding protein-3 (IGFBP-3) expression was observed. Changes in IGFBP-2 and IGFBP-3 mRNA expression were confirmed at the protein level by ELISA of DPC conditioned medium functional analysis indicated that IGF1 stimulated the differentiation of DPCs and that the activity of the growth factor was enhanced by pre-complexation with IGFBP-2 but inhibited by pre-complexation with IGFBP-3. Therefore changes in IGFBP-2 and -3 expression during differentiation form part of a co-ordinated functional response to enhance the pro-differentiative action of IGF1 and represent a novel mechanism for the regulation of DPC differentiation.