Development of a low-cost silica-titania optical platform for integrated photonics applications.

This paper investigates a highly attractive platform for an optical waveguide system based on silica-titania material. The paper is organized into two parts. In the first part, an experimental study on the development of an optical waveguide system is conducted via the sol-gel dip-coating method, and the optical characterization of the waveguide system is performed at a visible wavelength. This system is capable of operating from visible to near-IR wavelength ranges. The experimental results prove the dominance of this waveguide platform due to its low-cost, low loss, and easy to develop integrated optics systems. The numerical analysis of a one-dimensional Photonic crystal waveguide optical filter based on the silica-titania platform is considered in the second part of the paper by utilizing the 2D-finite element method (2D-FEM). A Fabry-Perot structure is also analyzed for refractive index sensing applications. We believe that the results presented in this work will be valuable in the realization of low-cost photonic integrated circuits based on the silica-titania platform.

Is systemic inflammation a missing link between periodontitis and hypertension? Results from two large population-based surveys.

OBJECTIVE: The primary objective was to investigate the relationship between periodontitis and hypertension in two independent large surveys. The secondary objective was to ascertain whether systemic inflammation had a mediation effect in the association. METHODS: This cross-sectional study analysed representative samples of the US (n = 3460; NHANES 2009/10) and Korean (n = 4539; 2015 KNHANES VI-3) populations. The association between periodontitis (exposure), hypertension (outcome) and inflammatory markers [C-reactive protein (CRP) and white blood cell counts (WBC)] (mediators) was assessed using multivariate linear and logistic regression models and mediation analysis. RESULTS: Participants with periodontitis were more likely to have hypertension (NHANES: OR = 1.3, 95% CI: 1.0-1.6, P = 0.025; KNHANES: OR = 1.2, 95% CI: 1.0-1.4, P = 0.041) and actual systolic blood pressure ≥ 140 mmHg (NHANES: OR = 1.6, 95% CI: 1.1-2.3, P < 0.001; KNHANES: OR = 1.3, 95% CI :1.0-1.6, P < 0.031) than those without the disease. These associations were independent of age, gender, BMI, education level, smoking, alcohol consumption, creatinine, physical activity, presence of other comorbidities and confirmed in participants not taking antihypertensive medications. Diagnosis of periodontitis was directly associated with WBC (in both surveys: NHANES: ß ± SE = 0.3 ± 0.1, P < 0.004; KNHANES: ß ± SE = 0.3 ± 0.1, P < 0.001) and with CRP levels (in one survey: NHANES: ß ± SE = 0.1 ± 0.03, P < 0.007; KNHANES: ß ± SE = 0.1 ± 0.04, P > 0.213). Mediation analyses confirmed that CRP acted as a mediator in the association between periodontitis and hypertension in both populations (mediated effect: NHANES: ß ± SE = 0.010 ± 0.003, P < 0.001; KNHANES: ß ± SE = 0.003 ± 0.001, P = 0.015). WBC acted as a mediator in the KNHANES (mediated effect: ß ± SE = 0.004 ± 0.001, P = 0.004) whilst in the NHANES, its effect was dependent of CRP inclusion in the model (mediated effect WBC + CRP: ß ± SE = 0.002 ± 0.001, P = 0.001). CONCLUSIONS: These findings suggest that periodontitis is closely linked to hypertension and systemic inflammation is, in part, a mediator of this association.

Extraordinary micro-endemism in Australian desert spring amphipods.

Increasing pressure for water in the Australian arid zone is placing enormous stress on the diverse endemic communities inhabiting desert springs. Detailed information about the evolutionary processes occurring within and between individual endemic species will help to develop effective and biologically relevant management strategies this fragile ecosystem. To help determine conservation priorities, we documented the genetic structure of the endemic freshwater amphipod populations in springs fed by the Great Artesian Basin in central Australia. Phylogenetic and phylogeographic history and genetic diversity measures were examined using nuclear and mitochondrial DNA from approximately 500 chiltoniid amphipods across an entire group of springs. Pronounced genetic diversity was identified, demonstrating that levels of endemism have been grossly underestimated in these amphipods. Using the GMYC model, 13 genetically divergent lineages were recognized as Evolutionarily Significant Units (ESUs), all of which could be considered as separate species. The results show that due to the highly fragmented ecosystem, these taxa have highly restricted distributions. Many of the identified ESUs are endemic to a very small number of already degraded springs, with the rarest existing in single springs. Despite their extraordinarily small ranges, most ESUs showed relative demographic stability and high levels of genetic diversity, and genetic diversity was not directly linked to habitat extent. The relatively robust genetic health of ESUs does not preclude them from endangerment, as their limited distributions ensure they will be highly vulnerable to future water extraction.

Patterns of population genetic variation in sympatric chiltoniid amphipods within a calcrete aquifer reveal a dynamic subterranean environment.

Calcrete aquifers from the Yilgarn region of arid central Western Australia contain an assemblage of obligate groundwater invertebrate species that are each endemic to single aquifers. Fine-scale phylogeographic and population genetic analyses of three sympatric and independently derived species of amphipod (Chiltoniidae) were carried out to determine whether there were common patterns of population genetic structure or evidence for past geographic isolation of populations within a single calcrete aquifer. Genetic diversity in amphipod mitochondrial DNA (cytochrome c oxidase subunit I gene) and allozymes were examined across a 3.5 km(2) region of the Sturt Meadows calcrete, which contains a grid of 115 bore holes (=wells). Stygobiont amphipods were found to have high levels of mitochondrial haplotype diversity coupled with low nucleotide diversity. Mitochondrial phylogeographic structuring was found between haplogroups for one of the chiltoniid species, which also showed population structuring for nuclear markers. Signatures of population expansion in two of the three species, match previous findings for diving beetles at the same site, indicating that the system is dynamic. We propose isolation of populations in refugia within the calcrete, followed by expansion events, as the most likely source of intraspecific genetic diversity, due to changes in water level influencing gene flow across the calcrete.

Orthodontic treatment in patients with periodontitis - a narrative literature review.

Patients with periodontitis often require an inter-disciplinary approach, including orthodontic treatment, for effective rehabilitation of masticatory function, aesthetics and quality of life. The aim of this narrative review was to comprehensively discuss literature focusing on the biology, indications and inter-disciplinary connections related to the orthodontic approach in patients with periodontitis and to present clinical concepts in accordance with valid guidelines. The outcomes of the experimental studies indicate that orthodontic tooth movement (OTM) can be performed safely for teeth with reduced periodontium, provided infection and inflammation are controlled. Orthodontic treatment can correct pathological tooth migration, is not associated with deterioration of clinical periodontal parameters and improves aesthetics. Intrusion is safe when performed with light forces and under a strict oral hygiene regimen. Teeth can be moved either towards or away from the intrabony defect previously subjected to regenerative procedures, and research suggests that OTM has the potential to enhance bone formation after regenerative therapy. The data on orthodontic movement of teeth with furcation involvement are very scarce. The improvement in furcation involvement following either combined periodontal and orthodontic treatment was only documented in animal model studies. Due to bone and tooth loss, special consideration should be given to orthodontic treatment mechanics. © 2023 Australian Dental Association.

What lies beneath: molecular phylogenetics and ancestral state reconstruction of the ancient subterranean Australian Parabathynellidae (Syncarida, Crustacea).

The crustacean family Parabathynellidae is an ancient and significant faunal component of subterranean ecosystems. Molecular data were generated in order to examine phylogenetic relationships amongst Australian genera and assess the species diversity of this group within Australia. We also used the resultant phylogenetic framework, in combination with an ancestral state reconstruction (ASR) analysis, to explore the evolution of two key morphological characters (number of segments of the first and second antennae), previously used to define genera, and assess the oligomerization principle (i.e. serial appendage reduction over time), which is commonly invoked in crustacean systematics. The ASR approach also allowed an assessment of whether there has been convergent evolution of appendage numbers during the evolution of Australian parabathynellids. Sequence data from the mtDNA COI and nDNA 18S rRNA genes were obtained from 32 parabathynellid species (100% of described genera and ~25% of described species) from key groundwater regions across Australia. Phylogenetic analyses revealed that species of each known genus, defined by traditional morphological methods, were monophyletic, suggesting that the commonly used generic characters are robust for defining distinct evolutionary lineages. Additionally, ancestral state reconstruction analysis provided evidence for multiple cases of convergent evolution for the two morphological characters evaluated, suggesting that caution needs to be shown when using these characters for elucidating phylogenetic relationships, particularly when there are few morphological characters available for reconstructing relationships. The ancestral state analysis contradicted the conventional view of parabathynellid evolution, which assumes that more simplified taxa (i.e. those with fewer-segmented appendages and setae) are derived and more complex taxa are primitive.

Evidence for population fragmentation within a subterranean aquatic habitat in the Western Australian desert.

The evolution of subterranean animals following multiple colonisation events from the surface has been well documented, but few studies have investigated the potential for species diversification within cavernicolous habitats. Isolated calcrete (carbonate) aquifers in central Western Australia have been shown to contain diverse assemblages of aquatic subterranean invertebrate species (stygofauna) and to offer a unique model system for exploring the mechanisms of speciation in subterranean ecosystems. In this paper, we investigated the hypothesis that microallopatric speciation processes (fragmentation and isolation by distance (IBD)) occur within calcretes using a comparative phylogeographic study of three stygobiontic diving beetle species, one amphipod species and a lineage of isopods. Specimens were sequenced for the mitochondrial cytochrome c oxidase 1 gene from three main sites: Quandong Well, Shady Well (SW) and Mt. Windarra (MW), spanning a 15 km region of the Laverton Downs Calcrete. Phylogenetic and haplotype network analyses revealed that each species possessed a single divergent clade of haplotypes that were present only at the southern MW site, despite the existence of other haplotypes at MW that were shared with SW. IBD between MW and SW was evident, but the common phylogeographic pattern most likely resulted from fragmentation, possibly by a salt lake adjacent to MW. These findings suggest that microallopatric speciation within calcretes may be a significant diversifying force, although the proportion of stygofauna species that may have resulted from in situ speciation in this system remains to be determined.

Fine-scale comparative phylogeography of a sympatric sister species triplet of subterranean diving beetles from a single calcrete aquifer in Western Australia.

Calcrete aquifers in the arid Yilgarn region of central Western Australia are a biodiversity hotspot for stygofauna. A distinct pattern of interspecific size class variation among subterranean dytiscid beetle species has been observed in 29 of these aquifers where either two or three small, medium and/or large sympatric species are found that are in some cases sister species. We used a 3.5 km(2) grid of bores to sample dytiscids on a fine-scale and employed a comparative phylogeographical and population genetic approach to investigate the origins of a sympatric sister species triplet of diving beetles from a single aquifer. Mitochondrial DNA sequence data from the Cytochrome oxidase c subunit I gene revealed that all three species have high levels of haplotype diversity with ancient (approximately 1 million years ago) intra-specific coalescence of haplotypes, but low levels of nucleotide diversity. Population analyses provide evidence for multiple expansion events within each species. There was spatial heterogeneity in the distribution of genetic variation and abundance both within and among the three taxa. Population analyses revealed significant fine-scale differentiation with isolation by distance for Paroster macrosturtensis and P. mesosturtensis, but not the smallest species P. microsturtensis. Haplotype network analyses provided limited or no evidence for past population fragmentation within the large and small species, but substantial historical divergence was observed in P. mesosturtensis that was not spatially structured. A patchy population structure with contemporaneous and historical isolation by distance in the three species is likely to have been a significant isolating and diversifying force, preventing us from ruling out a potential role for allopatric divergence during speciation of this beetle sister triplet.

Dielectric and magnetic characteristics of Ca1-x Mn x MoO4 (0 ≤ x ≤ 0.15) nanomaterials.

Scheelite-type Ca1-x Mn x MoO4 (x = 0.0, 0.01, 0.05, 0.10 and 0.15) nanomaterials were successfully synthesized via a combustion route. Dielectric studies showed a weak n-type electrical conductivity characteristic for insulators and low relative permittivity (ε r < 15) decreasing with increasing Mn2+ content. CaMoO4 and Mn2+-doped nanomaterials are chemically compatible with Al and Ag electrodes and promising for low-temperature co-fired ceramic applications. Magnetic studies showed, at room-temperature diamagnetism for pure CaMoO4, the balance between diamagnetism and paramagnetism for Ca1-x Mn x MoO4 (x = 0.01) and paramagnetic behaviour when 0.05 ≤ x ≤ 0.15 as well as the short-range antiferromagnetic interactions growing in strength as Mn2+ content increases. The Landé factor fitting procedure showed a spin-only contribution to the magnetic moment. CaMoO4 matrix unexpectedly revealed the residual paramagnetism at low temperatures derived probably from the molybdenum ions having unpaired 4d electrons as well as a paramagnetic-diamagnetic transition at 70 K.

Effects of controlled physical activity on immune cell phenotype in peripheral blood in prehypertension - studies in preclinical model and randomised crossover study.

Hypertension (HT) is a global public health issue. There are many behavioural risk factors including unhealthy diet, tobacco use and alcohol consumption as well physical inactivity that contribute to the development of high blood pressure (BP) and its complications. Favourable effect of regular physical activity on treatment or prevention of hypertension by improvement of endothelial function is widely accepted however little is known about its relationship with immune system. Thus, the aim of this study was to assess the role of moderate regular physical activity on immune cell phenotype. T cell and monocyte subsets were characterised in 31 subjects with prehypertension (130 - 139 mmHg systolic and 85 - 89 mmHg diastolic blood pressure) who participated in moderate training (3 times/week) on cyclometers for 3 months in crossover study design. Complementary study was performed in murine model of Ang II-induced hypertension and ten-week-old animals were trained on a treadmill (5 times/week, 1 hour) for 2 weeks before and 1.5 weeks after minipumps implantation. In the context of elevated blood pressure regular physical activity had modest influence on immune cell phenotype. Both in human study and murine model we did not observe effects of applied exercise that can explain the mechanism of BP reduction after short-term regular training. Twelve-weeks regular training did not affect the activation status of T lymphocytes measured as expression of CD69, CD25 and CCR5 in human study. Physical activity resulted in higher expression of adhesion molecule CD11c on CD16+ monocytes (especially CD14 high) without any changes in leukocytes subpopulation counts. Similar results were observed in murine model of hypertension after the training. However the training caused significant decrease of CCR5 and CD25 expressions (measured as a mean fluorescence intensity) on CD8+ T cells infiltrating perivascular adipose tissue. Our studies show modest regulatory influence of moderate training on inflammatory markers in prehypertensive subjects and murine model of Ang II induced hypertension.

Melatonin and its role in oxidative stress related diseases of oral cavity.

The role of the oral cavity in the pathogenesis of diseases of various systems such as the gastro-intestinal tract (GIT), cardiovascular and immune systems has been recently evaluated. While initially the oral cavity was considered to be mainly a source of various bacteria, their toxins and antigens, recent studies showed that it may also be a location of oxidative stress and periodontal inflammation. Accordingly, this review focuses on the involvement of melatonin (MT) in oxidative stress diseases of oral cavity as well as on potential therapeutic implications of MT in dental disorders, especially in periodontal inflammation. MT is generated and released by pineal gland and by entero-endocrine (EE) cells located in the GIT. The pattern of MT secretion from the pineal gland is controlled by an endogenous circadian timing system that conveys information about the light/dark cycle to various organs of the body, thereby organizing its seasonal and circadian rhythms. The secretion of MT from the EE cells of GIT is related mainly to feeding periods. MT is a non-toxic highly lipophilic indole, and this feature facilitates its penetration through cell membranes and its compartments. However, the most important effect of MT seems to result from its potent antioxidant, immuno-modulatory, protective and anti-cancer properties. It stimulates synthesis of type I collagen fibers and promotes bone formation. Thus, MT could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal or viral origin, in post-surgical wounds caused by tooth extractions and other oral surgeries and, in helping bone formation in various auto-immunological disorders such as Sjorgen syndrome, in periodontal diseases, and in oral cancers.

Localization and biological activities of melatonin in intact and diseased gastrointestinal tract (GIT).

Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, cytoprotective, anti-inflammatory and healing efficacy of various GIT lesions such as esophagitis, gastritis, peptic ulcer, pancreatitis and colitis. This review concentrates on the generation and pathophysiological implication of MT in GIT and related organs.

Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves.

Melatonin (MT) is known to protect gastrointestinal mucosa against various types of injury but its effects on esophageal damage have not been studied. We examined the effects of MT on acute esophageal injury and the mechanism involved in the action of this indole. Acute esophageal lesions were induced by perfusion with acid-pepsin solution using tube inserted through the oral cavity into the mid of esophagus of anaesthetized rats with or without inhibition of prostaglandin (PG) generation by indomethacin (5 mg/kg/day), nitric oxide (NO) formation by N(G)-nitro-L-arginine (L-NNA, 20 mg/kg/day) or sensory nerves deactivation by capsaicin (125 mg/kg, sc). The esophageal injury was assessed by macroscopic score and histologic activity index. The esophageal mucosal blood flow (EBF) was determinated by H(2)-gas clearance method. The plasma TNF-alpha and nitrate/nitrite (NOx) levels and mucosal PGE(2) contents were assessed by immunoassays. Esophageal acid-pepsin perfusion induced noticeable esophageal mucosal injury as compared to perfusion with vehicle saline. The pretreatment with MT prevented significantly esophageal injury, raised EBF and mucosal content of PGE(2), while decreasing the levels of TNF-alpha. Inhibition of COX/PG and NOS/NO systems by indomethacin and L-NNA, respectively, or inactivation of sensory nerves by capsaicin, that manifested in further increase of esophageal injury, reduced the levels of EBF, markedly raised the levels TNF-alpha and reduced mucosal PGE(2), but the pretreatment with MT prevented significantly esophageal injury, improved EBF and raised mucosal PGE(2) contents. These studies suggest that MT can be considered as a novel esophagoprotector, acting, at least in part, through the COX/PG and NOS/NO systems and activation of sensory nerves.

Anti-atherosclerotic effect of the angiotensin 1-7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis.

BACKGROUND AND PURPOSE: Inflammation plays a key role in atherosclerosis. The protective role of angiotensin 1-7 (Ang-(1-7)) in vascular pathologies suggested the therapeutic use of low MW, non-peptide Ang-(1-7) mimetics, such as AVE0991. The mechanisms underlying the vaso-protective effects of AVE0991, a Mas receptor agonist, remain to be explored. EXPERIMENTAL APPROACH: We investigated the effects of AVE0991 on the spontaneous atherosclerosis in apolipoprotein E (ApoE)-/- mice, in the context of vascular inflammation and plaque stability. KEY RESULTS: AVE0991 has significant anti-atherosclerotic properties in ApoE-/- mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using the descending aorta of chow-fed ApoE-/- mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (PVAT) and adventitial infiltration with macrophages and T-cells precedes atherosclerotic plaque or the impairment of endothelium-dependent NO bioavailability (a measure of endothelial function). AVE0991 inhibited perivascular inflammation, by reducing chemokine expression in PVAT and through direct actions on monocytes/macrophages inhibiting their activation, characterized by production of IL-1ß, TNF-α, CCL2 and CXCL10, and differentiation to M1 phenotype. Pretreatment with AVE0991 inhibited migration of THP-1 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in PVAT and in THP-1 cells in vitro, and the anti-inflammatory effects of AVE0991 were partly Mas dependent. CONCLUSIONS AND IMPLICATIONS: The selective Mas receptor agonist AVE0991 exhibited anti-atherosclerotic and anti-inflammatory actions, affecting monocyte/macrophage differentiation and recruitment to the perivascular space during early stages of atherosclerosis in ApoE-/- mice. LINKED ARTICLES: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.

Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis.

Superoxide anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent of it's ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not lead to their abrogation.

Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels.

UNLABELLED: Venous bypass grafts are more prone to accelerated atherosclerosis than arterial grafts, which is partly related to increased oxidative stress and diminished nitric oxide bioavailability. In veins superoxide production is dependent primarily on nox2 NAD(P)H oxidase expression, while in arteries nox4 appears to play an important role. This may in part explain differences in susceptibility to graft failure. Net levels of oxidative stress are however determined in parallel by the production as well as by degradation of free radicals (eg. by superoxide dismutases, catalases, thioredoxins etc). The differences in superoxide dismutase (SOD) expression and activity in human bypass conduit vessels remain unclear. Accordingly, we aimed to compare SOD activity and protein levels as well as its functional effects on superoxide production in segments of human internal mammary arteries (IMA) and saphenous veins (HSV) from patients undergoing bypass graft surgery (n=24). SOD activity was assessed by inhibition of pyrogallol autoxidation, Cu-Zn SOD and Mn SOD protein levels were studied by immunoblotting. Basal superoxide release was detected by lucigenin (5 microM) enhanced chemiluminescence. Total SOD activity did not differ significantly between HSV and IMA. Similarly, no difference was observed in SOD activity in the presence of KCN (Mn-SOD). Human bypass conduit vessels show amounts of Cu-Zn SOD or Mn-SOD protein levels. In both HSV and IMA segments superoxide production was more than doubled in the presence of SOD inhibitor-DETC. CONCLUSIONS: These studies suggest that the differences in oxidative stress between human arteries and veins are unlikely to be caused by SOD activity. However SOD plays and important role in amelioration of oxidative stress in both types of vessels.

Prevalence and characterization of Helicobacter pylori (H. pylori) infection and colonization in dentists.

H. pylori is an important factor in the pathogenesis of numerous diseases including gastro-intestinal, metabolic and vascular disorders. Therefore, identification of individuals at risk of this infection remains of critical importance. Dentists and dental professionals may be at increased risk due to the contact with oral cavity of patients with the presence of H. pylori in the oral cavity where it may serve as reservoir for gastric infections and participate in the pathogenesis oral mucosal lesions and ulceration. However, evidence regarding the occurrence of H. pylori infections and colonization in dentists is conflicting, but has been based mainly on serological studies, which carry significant limitations. Therefore, we attempted to characterize H. pylori infection in practising dentists in relation to the duration of their work as dental professionals. Moreover, apart from seropositivity, which was used by majority of previous studies, we have performed urea-breath test (UBT), which has been shown to represent active H. pylori infection in stomach as well as the H. pylori culture from the oral cavity. We found that while the occurrence of either gastric or oral H. pylori in dentists is not greater than in general population, it seems that in male dentists there is a greater risk of gastric H. pylori infection. Moreover, we found a relationship between the length of dentist occupation with the presence of H. pylori in gingival sulcus. In conclusion, while overall occurrence of H. pylori in dentists did not differ from that reported for stomach or oral cavity in general population, there was an increased occurrence of H. pylori in male dentists and the presence of this germ in the oral cavity appears to be related to the length of professional exposure.

NADPH oxidase and uncoupled nitric oxide synthase are major sources of reactive oxygen species in oral squamous cell carcinoma. Potential implications for immune regulation in high oxidative stress conditions.

The development of cancer is associated with high oxidative stress and at the same time with immune system activation. Tumors develop efficient mechanisms of protection against the immune response, which allow them to escape the immune surveillance. Simultaneously, key events in the process of carcinogenesis are related to oxidative stress. The relationship between the two remains unknown. Novel understanding of oxidative stress shows that discrete changes of activities of certain enzyme systems such as NADPH oxidases or nitric oxide synthases may be more important than the overall balance of production and removal of reactive oxygen species. Such imbalance of nitric oxide and superoxide production could modify inflammation and immune regulation. We studied superoxide anion production (by lucigenin enhanced chemiluminescence - 5 microM), NADPH oxidase activity and nitric oxide synthase (NOS) dysfunction. In parallel mRNA expression of immunomodulatory markers such as FoxP3 (T regulatory cell marker), CCR6 (mucosal homing effector T cell marker) and CD85j (NK cell/CD8 T cell Ig-like MHC class I inhibitory receptor) was determined. Basal superoxide production and NADPH oxidase activity are increased in oral squamous cell carcinoma. Tumor superoxide production was inhibited by NADPH oxidase inhibitor apocynin and by NOS inhibitor L-NAME. This indicates, for the first time, that oral squamous cell carcinoma is characterized by dysregulated nitric oxide synthase, which apart from increased NADPH oxidase activity contributes to oxidative stress and may be related to the immuno-pathology of these tumors. Studied tumors were infiltrated by CCR6+, but showed lower expression of both CD85j and FoxP3 mRNA. Finally, the CD85j mRNA expression was inversely correlated to oxidative stress parameters. These preliminary studies indicate that tumor oxidative stress, related to NADPH oxidase activity and NOS activity could be related to immune responses to cancer, thus therapeutic modification of oxidative stress, which could include the correction of NOS dysfunction, could facilitate immune surveillance.

Perivascular adipose tissue as a messenger of the brain-vessel axis: role in vascular inflammation and dysfunction.

Perivascular adipose tissue AT is a critical regulator of vascular function, which until recently has been greatly overlooked. Virtually all arteries are surrounded by a significant amount of perivascular adipose tissue, which has long been considered to serve primarily a supportive, mechanical purpose. Recent studies show that both visceral and perivascular fat is a very active endocrine and paracrine source of inflammatory cytokines and adipokines. The latter include beneficial adipocytokines such as adiponectin or so far unidentified adipocyte derived relaxing factor (ADRF) as the presence of perivascular AT may decrease contractile responses to vasoconstrictive agents. However, in pathological states such as obesity, hypertension, diabetes metabolic syndrome and other cardiovascular disorders perivascular tissue becomes dysfunctional and production of protective factors diminishes while detrimental adipocytokines such as leptin, resistin, IL-6, TNF-alpha or IL-17 increases. Moreover the dysfunction of perivascular fat can lead to imbalance between vascular nitric oxide (NO) and superoxide production. Adipokines also regulate immune system as chemokines (such as MIP-1 or RANTES) and induce inflammation with infiltration of T cells and macrophages to the vessel wall. Interestingly central nervous system can affect vascular function through mediation of perivascular adipose tissue dysfunction. In particular sympathetic nervous system endings are present in both visceral and perivascular AT. This powerful relationship between the brain and the vessel can be termed "brain-vessel axis" in which--we propose in the Review--perivascular adipose tissue may take center stage. The role of perivascular fat in the regulation of blood vessels depends on metabolic state, inflammation and clinical risk factors. In health protective and vasorelaxant properties of perivascular AT dominate while in pathology pathogenetic influences including neural stimulation of sympathetic nerve endings or humoral effects of certain hormones and adipocytokines dominates. We propose to term this state "perivascular adipose tissue dysfunction" in similarity to endothelial dysfunction.

The relationship between the presence of Helicobacter pylori in the oral cavity and gastric in the stomach.

There are numerous studies suggesting that inflammation of the oral cavity caused by bacteria or fungi is accompanied by gastric inflammation. This is particularly relevant in patients using complete dentures. Since the presence of H. pylori in the oral cavity can be easily discovered by bacteria culture and that in the stomach by (13)C urea breath test (UBT) and histology of gastric endoscopic biopsy samples it is reasonably to state that the majority of the patients show the presence of bacterium in oral cavity and active gastric H. pylori infection. When comparing, however, the bacteria culture originating from the oral mucosa to those from the gastric mucosa, employing molecular biology examination, such as polymerase chain reaction (PCR), we found that the oral bacteria and those originating from stomach are completely different, suggesting that H. pylori may be present only transiently in oral cavity and does not play major role in gastric H. pylori infection. Thus, oral cavity does not serve as bacterial reservoir to infect gastric mucosa. Most important finding of our study is that patients with recognized inflammation in the oral cavity in the form of stomatitis prothetica hyperplasica both fibrosa as well as papillaris showed in nearly 100% gastric H. pylori infection, usually without the presence of the same bacterium in the oral cavity, suggesting that gastric H. pylori infection affects oral mucosa at distance by some, as yet, unknown mechanism.