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.

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.

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.

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.

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.

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.

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.

Helicobacter pylori and its involvement in gastritis and peptic ulcer formation.

Modern gastroenterology started in early 19(th) century with the identification by W. Prout of the inorganic (hydrochloric) acid in the stomach and continued through 20(th) century with the discoveries by I.P. Pavlov of neuro-reflex stimulation of gastric secretion for which he was awarded first Nobel Prize in 1904. When concept of nervism or complete neural control of all digestive functions reached apogeum in Eastern Europe, on the other side of Europe (in United Kingdom), E. Edkins discovered in 1906 that a hormone, gastrin, may serve as chemical messenger in stimulation of gastric acid secretion, while L. Popielski revealed in 1916 that histamine is the most potent gastric secretagogue. K. Schwartz, without considering neural or hormonal nature of gastric secretory stimulation, enunciated in 1910 famous dictum; "no acid no ulcer"; and suggested gastrectomy as the best medication for excessive gastric acid secretion and peptic ulcer. In early 70s, J.W. Black, basing on earlier L. Popielski's histamine concept, identified histamine-H(2) receptors (H(2)-R) and obtained their antagonists, which were found very useful in the control of gastric acid secretion and ulcer therapy for which he was awarded in 1972 second Nobel Prize in gastrology. With discovery by G. Sachs in 1973 of proton pumps and their inhibitors (PPI), even more effective in gastric acid inhibition and ulcer therapy than H(2)-R antagonists, gastric surgery, namely gastrectomy, practiced since first gastric resection in 1881 by L. Rydygier, has been considered obsolete for ulcer treatment. Despite of the progress in gastric pharmacology, the ulcer disease remained essentially "undefeated" and showed periodic exacerbation and relapses. The discovery of spiral bacteria in the stomach in 1983 by B.J. Marshall and R.J. Warren, Australian, clinical researches, awarded in 2005 the Nobel Prize for the third time in gastrology, has been widely considered as a major breakthrough in pathophysiology of gastritis and peptic ulcer, which for the first time can be definitively cured by merely eradication of germ infecting stomach. This overview presents the mechanism of induction of gastritis and peptic ulcer by the H. pylori infection and describes accompanying changes in gastric acid and endocrine secretion as well as the effects of germ eradication on gastric secretory functions and gastroduodenal mucosal integrity.

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.

Involvement of Helicobacter pylori infection in neuro-hormonal control of food intake.

Ghrelin and leptin are endogenous peptides that have been implicated in the control of food intake, energy homeostasis and body weight gain. Although the stomach is the major source of circulating ghrelin and partly contributes also to plasma leptin, controversy exists over the influence of gastric Helicobacter pylori (Hp) infection on the ghrelin and leptin release. To resolve this controversy, plasma immunoreactive ghrelin and leptin levels were determined in Hp-positive and Hp negative children (N=60) and in adults (N=120) and daily concentrations of these hormones were measured at 2 h intervals before and after meals. Serum levels of ghrelin and leptin as well as gastrin were measured by RIA. Hp status was assessed using (13)C-urea breath test (UBT) and serology. Children with negative UBT showed significantly higher basal serum levels of ghrelin and lower concentrations of leptin than those with positive UBT. Adults without Hp infection also showed significantly higher fasting serum levels of ghrelin and lower levels of leptin than those in Hp infected subjects. In adults, especially without Hp infection, plasma levels of ghrelin showed a marked rise before the meal and sudden decrease following the food intake, while plasma leptin did not showed significant meal-related alterations, but in general its level was significantly higher in Hp positive than Hp negative subjects. Serum gastrin concentrations were significantly elevated in both Hp positive children and adults and these levels were significantly lower in Hp negative subjects. We conclude that Hp infection in children and adults causes a marked reduction in plasma levels of ghrelin, while increasing plasma levels of leptin and gastrin. These alterations in plasma levels of gastric originated appetite-controlling hormones in Hp infected children and adults may contribute to the alterations of the appetite and dyspeptic symptoms observed in these subjects.

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.

Neuro-hormonal control of food intake: basic mechanisms and clinical implications.

Obesity is one of the most common metabolic diseases and the greatest threats of the health because of possibility of numerous complications. In order to design effective drugs or apply the helpful surgical procedure it is essential to understand physiology of appetite control and pathophysiology of obesity. According to the first law of thermodynamics, the energy input in the form of food, equals energy expenditure through exercise, basal metabolism, thermogenesis and fat biosynthesis. The control of body weight actually concerns the control of adipose tissue with the key role of hypothalamus, possessing several neuronal centers such as that in lateral hypothalamic nuclei considered to be "hunger" center and in ventromedial nuclei serving as the "satiety" center. In addition, paraventricular and arcuate hypothalamic nuclei (ARC) are the sites where multiple hormones, released from the gut and adipose tissue, converge to regulate food intake and energy expenditure. There are two distinct types of neurons in ARC that are important in control of food intake; (1) preopiomelanocortin (POMC) neurons activated by an orexigenic hormones and releasing alpha-melanocyte-stimulating hormone (alpha-MSH) in satiety center and (2) neurons activated by orexigenic peptides such as ghrelin that release the substances including neuropeptide Y (NPY) and Agouti-Related Peptide (AgRP) in hunger center. ARC integrates neural (mostly vagal) and humoral inputs such as enteropeptides including orexigenic (ghrelin and orexins) and an orexigenic peptides (cholecystokinin, polypeptide YY, glucagon-like peptide-1, oxyntomodulin, leptin and others) that exert a physiological role in regulating appetite and satiety. The peripherally (gut, adipose tissue) and centrally expressed modulators of appetitive behavior act through specific receptors in the afferent (mostly vagal) nerves and hypothalamic neurons implicated in adiposity signaling and regulation of food intake.

Helicobacter pylori in the oral cavity and its implications for gastric infection, periodontal health, immunology and dyspepsia.

Helicobacter pylori (H. pylori) is an important gastrointestinal pathogen associated with gastritis as well as gastric or duodenal ulcers and gastric cancer. The oral cavity has been considered as a potential reservoir for the gastric infection and reinfection. The objective of our studies was to evaluate the influence of oral H. pylori for the stomach infection and the release of gut hormones affecting food intake such as ghrelin and gastric secretion such as gastrin. Additionally, the contribution of H. pylori in the periodontal disease has been examined. H. pylori infection in stomach was assessed by (13)C- Urease Breath Test and presence of the bacteria in oral cavity by culture. The periodontal status was measured by pockets depth with the periodontal probe. We estimated the serum level of IgG anti-H. pylori, anti-VacA, anti-CagA, ghrelin, gastrin, TNF-alpha and IL-8 in blood and the level of IgA anti-H. pylori in saliva. The presence of H. pylori in oral cavity was detected in 54.1% of examined individuals, whereas the H. pylori gastric infection in tested group was found in 51% cases. However, the correlation analysis between those two groups of patients involving together about 100 subjects showed that within the group of patients with positive gastric H. pylori infection only 45.1% did not show the presence of H. pylori in saliva and 43.1% showed no H. pylori in supragingival plaque. In line of these findings patients who did not have gastric H. pylori infection, 53.2% showed presence of H. pylori in saliva and 42.9% in supragingival plaques. Serum level of ghrelin and gastrin in subjects with oral H. pylori inoculation but without gastric H. pylori infection were not significantly different from those without the presence of this germ in oral cavity. In contrast, gastric H. pylori infection resulted in significant reduction in serum ghrelin levels and significant elevation of gastrin as compared to those who were gastric H. pylori negative. We concluded that oral H. pylori alone does not seem to serve as bacterium sanctuary for gastric H. pylori infection and, unlike gastric infection, it fails to affect serum levels of hormones stimulating appetitive behaviour such as ghrelin and gastric acid secretion such as gastrin.

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.

Association of the presence of Helicobacter pylori in the oral cavity and in the stomach.

UNLABELLED: Helicobacter pylori is a gram-negative, microaerophilic rod-shaped bacteria that lives beneath the gastric mucous layer, on the surface of epithelial cells. Stomach infection with this organism causes inflammation of the gastric mucosa, which can lead to gastritis, duodenal or gastric ulcer and even in rare cases to gastric carcinoma or MALT lymphoma. Approximately 50% of the world's population is believed to be infected with H. pylori. Most infections is probably acquired in childhood, but the exact route of transmission is unknown. It has been speculated that dental plaque might harbour Helicobacter pylori and, therefore, might be a source of gastric infection. In order to address this issue we studied the relationships between oral and gastric infections with H. pylori in 100 subjects. METHODS: Gastric H. pylori infection was determined by (13)C-urea breath test (UBT) and the presence of the bacteria in oral cavity was monitored by the culture from the saliva and from dental plaque. RESULTS: H. pylori was found in the stomach in 51% of studied individuals, while oral H. pylori was found in 54% (in saliva) and in 48.3% (in gingival pockets), the difference was not statistical significant (p=NS). Interestingly, anti-Hp IgA was found in 84% of studied individuals. No relationship was found between the presence of the bacteria in the oral cavity and the H. pylori gastric infection. 54.9% of subjects with stomach infection showed concomitant presence of H. pylori in saliva. 52.3% of examined subjects with negative UBT-test revealed the presence of H. pylori in culture from the saliva. The X(2) value of relationship between UBT and culture H pylori in saliva was 0.029 (p=0.9). Similarly, no relationship was found between the presence of H. pylori in the stomach and in the dental plaque (X2=0.6); p=0.4). As expected, the presence of H. pylori in the dental plaque was significantly correlated with the presence of bacteria in the saliva (X2=18.4; p=0.0002). We also compared the presence of H. pylori in the saliva of patients with and without teeth. The cultured H. pylori was found in 63.7% of patients without teeth and in 52.9% of patients with teeth. This indicates that the presence of teeth does not seem to affect the occurrence of H. pylori in saliva. We conclude that oral activity contamination with of H. pylori occurs at similar degree to that in the stomach. However, there was no significant correlation between the occurrence of H. pylori in the stomach and in the oral cavity indicating that other factors, like susceptibility to infection due to acid environment in the stomach may be the major factor in gastric infection with that bacteria, while oral cavity may serve only as transient food-related contamination without clear relation to gastric infection.