Periodontitis is a chronic non-communicable disease caused by dysbiotic changes that affect the subgingival microbiota. During periodontitis, neutrophils play a central role in the initial ...recognition of bacteria, and their number increases with the appearance of the first signs of periodontal inflammation. Recent evidence has led to the proposition that neutrophils can also functionally polarize, determining selective activity patterns related to different diseases. Two well-defined neutrophil phenotypes have been described, the pro-inflammatory N1 subset and the suppressor N2 subset. To date, it has not been established whether these different neutrophil subtypes play a role in the pathogenesis of periodontitis. Thus, this scoping review aimed to determine whether there was evidence to suggest that the neutrophils present in periodontal tissues can be associated with certain phenotypes. The research question, population, concept, and context sought to identify original articles, in humans, that detected the presence of neutrophils in the periodontal tissues of people affected by periodontitis. Based on the search strategy, we found 3658 studies. After removing the papers with abstracts not related to the outcome measures and eligibility criteria, 16 articles were included for qualitative analysis. Several studies identified the presence of different neutrophil subsets, specifically, the naive, pro- and para-inflammatory, hyper-reactive and hyper-active, and high- and low-responder phenotypes. The existing evidence demonstrates the presence of pro-inflammatory, hyper-reactive and high-responder neutrophils in periodontal tissues affected with periodontitis. There is no evidence demonstrating the presence of the N1 or N2 phenotypes in periodontal tissues during periodontitis. However, the existence of pro-inflammatory phenotypes, which increase NETosis and degranulation, and increase the production of pro-inflammatory cytokines, could be suggestive of the N1 phenotypes.
Periodontitis is considered a non-communicable chronic disease caused by a dysbiotic microbiota, which generates a low-grade systemic inflammation that chronically damages the organism. Several ...studies have associated periodontitis with other chronic non-communicable diseases, such as cardiovascular or neurodegenerative diseases. Besides, the oral bacteria considered a keystone pathogen,
Porphyromonas gingivalis
, has been detected in the hippocampus and brain cortex. Likewise, gut microbiota dysbiosis triggers a low-grade systemic inflammation, which also favors the risk for both cardiovascular and neurodegenerative diseases. Recently, the existence of an axis of Oral-Gut communication has been proposed, whose possible involvement in the development of neurodegenerative diseases has not been uncovered yet. The present review aims to compile evidence that the dysbiosis of the oral microbiota triggers changes in the gut microbiota, which creates a higher predisposition for the development of neuroinflammatory or neurodegenerative diseases.The Oral-Gut-Brain axis could be defined based on anatomical communications, where the mouth and the intestine are in constant communication. The oral-brain axis is mainly established from the trigeminal nerve and the gut-brain axis from the vagus nerve. The oral-gut communication is defined from an anatomical relation and the constant swallowing of oral bacteria. The gut-brain communication is more complex and due to bacteria-cells, immune and nervous system interactions. Thus, the gut-brain and oral-brain axis are in a bi-directional relationship. Through the qualitative analysis of the selected papers, we conclude that experimental periodontitis could produce both neurodegenerative pathologies and intestinal dysbiosis, and that periodontitis is likely to induce both conditions simultaneously. The severity of the neurodegenerative disease could depend, at least in part, on the effects of periodontitis in the gut microbiota, which could strengthen the immune response and create an injurious inflammatory and dysbiotic cycle. Thus, dementias would have their onset in dysbiotic phenomena that affect the oral cavity or the intestine. The selected studies allow us to speculate that oral-gut-brain communication exists, and bacteria probably get to the brain via trigeminal and vagus nerves.
Periodontitis is a low-grade inflammatory disease caused by a subgingival dysbiotic microbiota. Multiple studies have determined the higher prevalence of tooth loss and poor oral hygiene in patients ...with Alzheimer’s disease (AD). However, the periodontal diagnosis, periodontal bacteria or mediators has not been measured to date. Aim: To determine the periodontal status, the pro-inflammatory mediators, Porphyromonas gingivalis load, and Apoliporpotein E (ApoE) in patients with AD. A complete dental examination was performed on 30 patients, and cognitive status was determined by the Montreal Cognitive Assessment (MoCA). Subgingival microbiota and GCF samples were then taken from all patients from the deepest sites. Total DNA was isolated from the microbiota samples for the quantification of the 16S ribosomal subunit. Pro-inflammatory mediators and ApoE were quantified from the gingival crevicular fluid (GCF). Patients with AD had periodontitis stage III-IV in 80%, a higher concentration of pro-inflammatory and ApoE mediators, and a higher P. gingivalis load compared to healthy subjects. The pro-inflammatory mediators, P. gingivalis load had a negative correlation with the MoCA test scores. Finally, a ROC curve was performed to assess the specificity and sensitivity of ApoE levels, detecting an area of 84.9%. In AD patients, we found a more severe periodontitis, a higher levels of pro-inflammatory mediators, and higher bacterial load. In addition, there is an increase in ApoE that allows to clearly determine patients with health, periodontitis and periodontitis and AD.
Periodontitis and Alzheimer´s disease Sansores-España, D-; Carrillo-Avila, A; Melgar-Rodriguez, S ...
Medicina oral, patología oral y cirugía bucal,
2021-Jan-01, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Alzheimer's disease (AD), the main cause of dementia in the adult population, is characterized by a progressive loss of cognitive function. It is considered that neuroinflammation plays a fundamental ...role in its onset and progression. The bacteria present in the disbiotic microbiome generated during the course of periodontitis (PE) are capable of inducing a systemic inflammatory response, exacerbating the production of proinflammatory mediators that have the potential to spread to the systemic circulation.
A literature review was made using the databases Scielo, PubMed, EBSCO and key words "Alzheimer disease", "Periodontitis", "Neurodegeneration", "Inflammation mediators", "Elderly".
Several hypotheses point to similar pathophysiological pathways in the establishment of AD and PE, sharing cellular and molecular proinflammatory characteristics. In periodontitis, locally produced cytokines and pro-inflammatory products spread from the ulcerated periodontal pocket into the systemic circulation, or around the trigeminal nerve terminals, which allows the passage of bacteria or their products to the brain. This fact leads to the formation of plaques of amyloid peptide and intraneuronal neurofibrillar tangles (NFTs) that activate the glial cells producing a significant increase in proinflammatory cytokines in the affected regions that lead to a loss of neuronal synapses and neurodegeneration, contributing to the progression of AD.
This review of the literature contributes to the understanding of the pathological pathways shared by both diseases such as oxidative damage and inflammation. There is not enough evidence to determine an association between this two pathologies, so it is considered necessary to conduct studies for determine if periodontitis is capable of inducing or exacerbating the neuroinflammation that will trigger AD.
Range verification of clinical protontherapy systems via positron-emission tomography (PET) is not a mature technology, suffering from two major issues: insufficient signal from low-energy protons in ...the Bragg peak area and biological washout of PET emitters. The use of contrast agents including
O,
Zn or
Cu, isotopes with a high cross section for low-energy protons in nuclear reactions producing PET emitters, has been proposed to enhance the PET signal in the last millimeters of the proton path. However, it remains a challenge to achieve sufficient concentrations of these isotopes in the target volume. Here we investigate the possibilities of
O-enriched water (18-W), a potential contrast agent that could be incorporated in large proportions in live tissues by replacing regular water. We hypothesize that 18-W could also mitigate the problem of biological washout, as PET (
F) isotopes created inside live cells would remain trapped in the form of fluoride anions (F-), allowing its signal to be detected even hours after irradiation. To test our hypothesis, we designed an experiment with two main goals: first, prove that 18-W can incorporate enough
O into a living organism to produce a detectable signal from
F after proton irradiation, and second, determine the amount of activity that remains trapped inside the cells. The experiment was performed on a chicken embryo chorioallantoic membrane tumor model of head and neck cancer. Seven eggs with visible tumors were infused with 18-W and irradiated with 8-MeV protons (range in water: 0.74 mm), equivalent to clinical protons at the end of particle range. The activity produced after irradiation was detected and quantified in a small-animal PET-CT scanner, and further studied by placing ex-vivo tumours in a gamma radiation detector. In the acquired images, specific activity of
F (originating from 18-W) could be detected in the tumour area of the alive chicken embryo up to 9 h after irradiation, which confirms that low-energy protons can indeed produce a detectable PET signal if a suitable contrast agent is employed. Moreover, dynamic PET studies in two of the eggs evidenced a minimal effect of biological washout, with 68% retained specific
F activity at 8 h after irradiation. Furthermore, ex-vivo analysis of 4 irradiated tumours showed that up to 3% of oxygen atoms in the targets were replaced by
O from infused 18-W, and evidenced an entrapment of 59% for specific activity of
F after washing, supporting our hypothesis that F- ions remain trapped within the cells. An infusion of 18-W can incorporate
O in animal tissues by replacing regular water inside cells, producing a PET signal when irradiated with low-energy protons that could be used for range verification in protontherapy.
F produced inside cells remains entrapped and suffers from minimal biological washout, allowing for a sharper localization with longer PET acquisitions. Further studies must evaluate the feasibility of this technique in dosimetric conditions closer to clinical practice, in order to define potential protocols for its use in patients.
Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in ...range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate "FLASH" irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.
Key message
Two intercistronic regions were identified as functional intercistronic expression elements (IEE) for the simultaneous expression of
aphA-6
and
gfp
in a synthetic operon in the ...chloroplast of
C. reinhardtii
.
Chlamydomonas reinhardtii
, a biflagellate photosynthetic microalga, has been widely used in basic and applied science. Already three decades ago, Chlamydomonas had its chloroplast genome transformed and to this day constitutes the only alga routinely used in transplastomic technology. Despite the fact that over a 100 foreign genes have been expressed from the chloroplast genome, little has been done to address the challenge of expressing multiple genes in the form of operons, a development that is needed and crucial to push forward metabolic engineering and synthetic biology in this organism. Here, we studied five intercistronic regions and investigated if they can be used as intercistronic expression elements (IEE) in synthetic operons to drive the expression of foreign genes in the chloroplast of
C. reinhardtii
. The intercistronic regions were those from the
psbB
-
psbT, psbN
-
psbH, psaC
-
petL, petL
-
trnN
and
tscA
-
chlN
chloroplast operons, and the foreign genes were the aminoglycoside 3′-phosphotransferase (
aphA-6)
, which confers resistance to kanamycin, and the green fluorescent protein gene (
gfp)
. While all the intercistronic regions yielded lines that were resistant to kanamycin, only two (obtained with intercistronic regions from
psbN
-
psbH
and
tscA
-
chlN
) were identified as functional IEEs, yielding lines in which the second cistron (
gfp)
was translated and generated GFP. The IEEs we have identified could be useful for the stacking of genes for metabolic engineering or synthetic biology circuits in the chloroplast of
C. reinhardtii
.
We propose the use of 18O-enriched water as a suitable contrast agent for potential in-vivo range verification in proton therapy. The low energy production threshold of 18F (2.6 MeV, proton range in ...water of 115 μm) leads to tissue activation in very close proximity to the maximum dose deposition, facilitating accurate range verification with off-line PET imaging.
This idea has been explored in a phantom experiment. A 3D-printed phantom containing inserts with 18O-enriched water was irradiated with a 100-MeV, 8 × 8 cm2 proton beam, and the induced activity was measured with a small-animal PET-CT 30 min after irradiation. The images obtained were compared against Monte Carlo simulation using TOPAS.
Good agreement was observed between reconstructed and simulated activity profiles (within 40% for specific 18F activity), with excellent spatial match to the simulated dose deposition. Because of the long half-life of 18F, the specific activity of the contrast agent could be separated and was clearly observed for more than 2 h after irradiation. Activity distribution maps were used to determine the position of the Bragg peak within 2 mm for three different regions of interest. These results show the potential of 18O-enriched water as a contrast agent in proton therapy.
•18O could be used as a contrast agent for proton therapy range verification.•Phantom with 18O enriched water was irradiated 100-MeV protons and imaged with PET.•18O induced PET activity was observed for more than 2 h after irradiation.•Observed PET activity agreed with predictions from Monte Carlo TOPAS.•Activity distribution maps allowed us to locate Bragg peak position within 2 mm.
Ezeject is a plungerless syringe prefilled with lyophilized measles vaccine. Ezeject syringes were compared with standard 3-cc syringes and 10-dose measles vaccine vials in the vaccination of 884 ...Guatemalan infants 8-23 months of age. Vaccination was performed by experienced vaccinators and by individuals without prior vaccination experience who received 2.5-3 hours of training. The overall seroconversion rate following administration was 96%, regardless of the type of syringe used or of the experience of the vaccinator. No significant adverse events were observed in children vaccinated with the new syringes. Although incomplete emptying was noted in 87% of the Ezeject syringes used, this had no effect on the serologic response to measles vaccine. Aspiration for detection of blood before injection of the vaccine was performed significantly (P < .001) less frequently with Ezeject than with 3-cc syringes by both experienced and inexperienced personnel. Inexperienced vaccinators administered measles vaccine significantly faster (P < .001) with Ezeject than with 3-cc syringes, but the times were similar for experienced vaccinators. Ezeject is an acceptable alternative to standard syringes for the administration of measles vaccine. Several design modifications that would improve the handling of the device and eliminate the possibility of its reuse have been suggested.
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