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1.
Periodontol 2000 ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233381

RESUMEN

This review highlights the significance of interactions between the microbiota, immune system, nervous and hormonal systems, and the brain on periodontal health and disease. Microorganisms in the microbiota, immune cells, and neurons communicate via homeostatic nervous and hormonal systems, regulating vital body functions. By modulating pro-inflammatory and anti-inflammatory adaptive immune responses, these systems control the composition and number of microorganisms in the microbiota. The strength of these brain-controlled responses is genetically determined but is sensitive to early childhood stressors, which can permanently alter their responsiveness via epigenetic mechanisms, and to adult stressors, causing temporary changes. Clinical evidence and research with humans and animal models indicate that factors linked to severe periodontitis enhance the responsiveness of these homeostatic systems, leading to persistent hyperactivation. This weakens the immune defense against invasive symbiotic microorganisms (pathobionts) while strengthening the defense against non-invasive symbionts at the gingival margin. The result is an increased gingival tissue load of pathobionts, including Gram-negative bacteria, followed by an excessive innate immune response, which prevents infection but simultaneously destroys gingival and periodontal tissues. Thus, the balance between pro-inflammatory and anti-inflammatory adaptive immunity is crucial in controlling the microbiota, and the responsiveness of brain-controlled homeostatic systems determines periodontal health.

2.
Scand J Clin Lab Invest ; 72(7): 547-54, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22862430

RESUMEN

BACKGROUND: Toll-like receptor 4 (TLR4), especially expressed on monocytes/macrophages, connects microbial and sterile innate immune activation. Lipopolysaccharide (LPS) from Gram-negative bacteria and several endogenous molecules, among others saturated fatty acids (SFAs), are able to induce signalling through this receptor. Downstream inflammatory cytokines orchestrate the immune response. Our aim was to investigate how long-lasting multifactorial stress affects Gram-negative signalling and search for possible correlations between cytokine production and TLR4 expression or SFA concentration. METHODS: Eight healthy males were studied during a 7-day ranger-training course with semi-continuous physical strain, together with energy and sleep restrictions. Blood drawn on days 0, 3, 5 and 7 was incubated ex vivo for 6 h with or without LPS 10 ng/mL, whereupon surface expression of TLR4 on CD14⁺ monocytes and supernatant concentrations of inflammatory cytokines (TNF-α, IL-1ß and IL-6) were measured. In addition, plasma free fatty acids were quantified. RESULTS: Monocyte TLR4 expression was elevated throughout the course (p < 0.05 vs. baseline). Corresponding results were found for SFAs. The concentration of TNF-α increased significantly on day 3 and thereafter normalized, and a similar pattern was seen for IL-1ß. No correlations were found between cytokine concentrations and monocyte TLR4 expression or plasma SFAs. CONCLUSION: Multifactorial stress significantly affected ex vivo production of TNF-α and monocyte surface expression of TLR4. In addition, mobilization of fat resulted in increased plasma concentrations of SFAs. No associations between inflammatory cytokines and monocyte TLR4 expression or SFAs were found.


Asunto(s)
Bacterias Gramnegativas/metabolismo , Personal Militar , Transducción de Señal , Estrés Fisiológico , Ácidos Grasos no Esterificados/sangre , Citometría de Flujo , Humanos , Masculino
3.
Scand J Clin Lab Invest ; 72(3): 246-52, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22324831

RESUMEN

BACKGROUND: Alterations in body temperature may influence immune system function and consequently affect the risk of infection and inflammatory diseases. Lipopolysaccharide (LPS) from gram-negative bacteria induces production of inflammatory cytokines after ligand binding to Toll-like receptor 4 (TLR4) on immune cells (especially monocytes/ macrophages). Our aim was to explore how clinically relevant hypo- and hyperthermia affect this signalling in an ex vivo whole blood model, and investigate if the cytokine response was correlated with monocyte TLR4 expression level. METHODS: Blood from 11 healthy volunteers was incubated with LPS 10 ng/ml for 6 h at 33, 37 or 40°C. The concentrations of selected pro-inflammatory (tumour necrosis factor-α (TNF-α) and interleukin (IL)-1ß) and anti-inflammatory (IL-10) cytokines were measured in plasma, and the surface expression of TLR4 was quantified on CD14 + monocytes. RESULTS: Monocyte TLR4 expression and plasma IL-1ß were inversely related to temperature. The TNF-α production was unaffected by hypothermia but increased significantly during hyperthermia, whereas plasma IL-10 was significantly reduced during both hypo- and hyperthermic incubation. No correlation was found between TLR4 expression and cytokine concentrations. During hypothermia, the TNF-α/IL-10 and IL-1ß/IL-10 ratios increased seven and nine times, respectively. Hyperthermia increased the TNF-α/IL-10 ratio, but to a lesser extent (doubling), whereas the IL-1ß/IL-10 ratio remained unchanged. CONCLUSION: Hypothermia significantly changed the cytokine ratios in the pro-inflammatory direction. In comparison, the effect of hyperthermia was sparse, with a modest increase in the TNF-α/IL-10 ratio only. No association was found between LPS-stimulated cytokine production and TLR4 expression on CD14 + monocytes.


Asunto(s)
Hipertermia Inducida , Hipotermia/fisiopatología , Interleucina-10/biosíntesis , Interleucina-1beta/biosíntesis , Lipopolisacáridos/farmacología , Transducción de Señal/fisiología , Adulto , Supervivencia Celular , Citometría de Flujo , Humanos , Hipotermia/sangre , Masculino , Temperatura , Receptor Toll-Like 4/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis
4.
Scand J Pain ; 19(3): 441-451, 2019 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-30939119

RESUMEN

Background and aims Non-freezing cold injuries (NFCI), which typically may occur in military personnel, may result from exposure to cold, at temperatures around 0 °C or above, and worsened by wind and moisture. The injury is due to cooling but not freezing of tissue like in frostbite. NFCI may result in in chronic neuropathy and cold hypersensitivity. A recent retrospective study of small-and large fibres has suggested that NFCI results in neuropathic pain due to a sensory neuropathy and question a longitudinal study to verify a possible observation of improvement of NFCI over time. The present study is a 4-year follow-up investigation of large - and small-fibre function in 26 naval cadets and officers who were exposed to cold injury during the same military expedition. Methods The 26 soldiers were investigated clinically (with investigation of motor function, reflexes, sensibility), with nerve conduction studies (NCS) of major nerves in upper- and lower extremity, small fibre testing (QST, measurement of thermal thresholds), measurements of subcutaneous fat tissue and maximal O2 uptake. Investigations found place 2 months following the actual military expedition, with follow-up investigations of affected soldiers at 6-12 months and up to 3-4 years. In order to elucidate possible mechanisms (disinhibition of cold pain by myelinated nerve fibres) of cold allodynia, cold pain thresholds were measured following an ischemic block of conduction of large and small myelinated nerve fibres. Results Of 26 soldiers, 19 complained of numbness in feet and a large majority of 16 of cold hypersensitivity 2 months following injury. There were significant alterations of both large- and small-fibre function, indicating a general large- and small-fibre neuropathy. The most prominent finding was a pronounced cold allodynia, inversely correlated with the amount of subcutaneous fat. During the first year, results of NCS and thermal testing gradually normalized in most. Seven soldiers developed chronic symptoms in the form of cold hypersensitivity and with findings of cold allodynia, which was not further enhanced, but abolished following block of conduction of myelinated nerve fibres. Seven soldiers were free of symptoms from that start of the investigation, probably because they had been more eager to keep their legs moving during the exposure to cold. Conclusions Of a total of 26 soldiers, only seven developed chronic symptoms of cold hypersensitivity, corresponding to the finding of cold allodynia by thermal testing. The cold allodynia may not be explained by disinhibition of cold pain by myelinated fibres as in healthy subjects. A large majority recovered from an initial large-and small fibre neuropathy, demonstrating that recovery from NFCI may occur. Implications Although large-and small fibre neuropathy may be restored following cold injury, there is a risk of a permanent and disabling cold hypersensitivity, corresponding to the findings of cold allodynia. It is of uttermost importance to secure military personnel from the risk of cold injuries. It seems important to avoid immobilisation of extremities during exposure to cold.


Asunto(s)
Lesión por Frío/fisiopatología , Frío , Hiperalgesia/fisiopatología , Personal Militar , Neuralgia , Adulto , Estudios de Seguimiento , Humanos , Masculino , Fibras Nerviosas Mielínicas , Conducción Nerviosa/fisiología , Noruega , Umbral del Dolor , Adulto Joven
5.
Med Sci Sports Exerc ; 39(2): 275-82, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17277591

RESUMEN

INTRODUCTION: During the Norwegian military ranger-training course, cadets are exposed to prolonged physical exercise combined with sleep-, energy-, and food deficiency. The open-window postexercise hypothesis indicates that after hard physical activity, there is an increased risk of contracting infectious diseases. PURPOSE: The purpose of the present study was to determine leukocyte reactive oxygen species (ROS) levels, total antioxidant status (TAS), leukocyte expression of the cell adhesion molecules CD62L and CD11b, and plasma levels of soluble adhesion molecule L-selectin before, during, and in the recovery phase of a military ranger-training course. METHODS: Ten cadets from the Norwegian Military Academy were recruited to the study. Flow cytometry was used to study the intracellular levels of ROS in leukocytes (basally, as well as after in vitro stimulation with phorbol myristate acetate (PMA)), applying the probes dihydroethidium (DHE) and dihydrorhodamine 123 (DHR) and the leukocyte expression of adhesion molecules CD62L and CD11b. ELISA was used to assess the plasma levels of soluble L-selectin, and TAS in plasma was measured using the ABTS+ reduction assay kit. RESULTS: The basal levels of ROS as well as PMA-stimulated ROS in leukocytes declined gradually during the ranger-training course, being lowest on the last day (P < 0.05). The level of TAS increased (P < 0.01) during the course. A striking decrease (P < 0.001) was observed in leukocyte CD62L expression and was sustained even after 3 d of recovery. The leukocyte expression of CD11b remained unchanged. CONCLUSION: The ranger-training course leads to a partial exhaustion of the leukocyte ROS-generating machinery and to a nearly total extinguishing of leukocyte CD62L expression. These changes may support the open-window hypothesis indicating reduced ability to combat microbial invasions before total restitution.


Asunto(s)
Antígeno CD11b/biosíntesis , Ejercicio Físico/fisiología , Selectina L/biosíntesis , Recuento de Leucocitos , Especies Reactivas de Oxígeno , Privación de Sueño/sangre , Inanición/sangre , Adulto , Antígeno CD11b/sangre , Moléculas de Adhesión Celular/biosíntesis , Moléculas de Adhesión Celular/sangre , Citometría de Flujo , Humanos , Selectina L/sangre , Masculino , Personal Militar , Actividad Motora , Noruega , Estudios Prospectivos , Factores de Tiempo
6.
Am J Clin Nutr ; 83(5): 1068-75, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16685048

RESUMEN

BACKGROUND: A challenging 7-d ranger field exercise (FEX) by cadets in the Norwegian Military Academy provided a venue in which to study the effects of negative energy balance. OBJECTIVE: We quantified total energy expenditure (TEE), food intake, and changes in body composition in male and female cadets. DESIGN: TEE (measured by doubly labeled water), food intake, activity patterns (measured by accelerometry), and body composition (measured by dual-energy X-ray absorptiometry) were measured in 16 cadets (10 men and 6 women aged 21-27 y). RESULTS: The physically active (approximately 23 h/d) and semistarved (0.2-2.2 MJ/d) cadets lost weight (x +/- SD: men, -7.7 +/- 1.1 kg; women, -5.9 +/- 1.1 kg; P < 0.05). Absolute TEE differed by sex (men, 26.6 +/- 2.0 MJ/d; women, 21.9 +/- 2.0 MJ/d; P < 0.05) but body weight-specific TEE did not (men, 343 +/- 26 kJ . kg(-1) . d(-1); women, 354 +/- 18 kJ . kg(-1) . d(-1); NS). Fat-free mass (FFM) loss differed significantly by sex (men, -4.0 +/- 1.2 kg; women, -2.5 +/- 1.1 kg; P < 0.05), but percentage FFM loss did not (men, -6.3 +/- 1.9%; women, -5.6 +/- 2.4%). In contrast, absolute FM loss did not differ significantly by sex (men, -3.45 +/- 0.72 kg; women, -3.42 +/- 0.22 kg), but fat oxidation (men, 5.2 +/- 1.0 mg . min(-1) . kg FFM(-1); women, 7.3 +/- 0.5 mg . min(-1) . kg FFM(-1)) and the relative contribution of FM to TEE (men, 74 +/- 14%; women, 89 +/- 6%) were significantly greater in women than in men (P < 0.05). CONCLUSION: Female cadets maintained a significantly more fat-predominant fuel metabolism than did male cadets in response to sustained exercise and semistarvation.


Asunto(s)
Metabolismo Energético , Ejercicio Físico/fisiología , Privación de Alimentos/fisiología , Personal Militar , Absorciometría de Fotón , Tejido Adiposo , Adulto , Composición Corporal , Agua Corporal/fisiología , Peso Corporal , Femenino , Humanos , Masculino , Noruega , Oxidación-Reducción , Isótopos de Oxígeno , Caracteres Sexuales
7.
J Sports Med (Hindawi Publ Corp) ; 2016: 7186137, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27239554

RESUMEN

The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P < 0.001). LPS stimulation among the half-marathon runners decreased the postrace levels of IL-6, IL-1b, and TNFα by 45%, 24%, and 43%, respectively (P < 0.01). During the ranger training course the spontaneous and LPS-stimulated levels of IL-6, IL-8, IL-10, IL-1b, and TNFα changed in a similar fashion as in the half-marathon runners although the fluctuations were smaller. Our study supports the open window and the J-curve theory; the immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise.

8.
Mil Med ; 181(11): e1499-e1507, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27849483

RESUMEN

Human performance enhancement was the subject of a NATO workshop that considered the direct benefits of individual soldier health and fitness habits to brain health and performance. Some of the important health and fitness include physical activity and purposeful exercise, nutritional intake, sleep and rest behaviors, psychological outlook and mindfulness, and other physiologically based systemic challenges such as thermal exposure. These influences were considered in an integrated framework with insights contributed by each of five participating NATO member countries using representative research to highlight relevant interrelationships. Key conclusions are that (1) understanding the neurobiological bases and consequences of personal health behaviors is a priority for soldier performance research, and this also involves long-term brain health consequences to veterans and (2) health and fitness habits have been underappreciated as reliably effective performance enhancers and these should be preferred targets in the development of scientifically based recommendations for soldier brain health and performance.


Asunto(s)
Encéfalo/fisiología , Conductas Relacionadas con la Salud , Metabolismo/fisiología , Personal Militar/psicología , Análisis y Desempeño de Tareas , Adaptación Psicológica , Técnica Delphi , Hábitos , Humanos , Aptitud Física/fisiología
9.
Resuscitation ; 64(3): 377-82, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15733769

RESUMEN

Polytrauma and resuscitative efforts induce extensive alterations in the host's internal environment and cellular responses that may be a serious threat to these patients. Administration of exogenous thiols has been recommended to modulate the post-traumatic inflammatory responses. In this study, we have investigated the effect of N-acetylcysteine (NAC) on the early markers of leukocyte activation and subsequent endotoxin hyporesponsiveness. Twenty-eight pigs were exposed to a standardized gunshot injury. First aid treatment and initial life saving surgery was started without delay. One group (n = 14) was randomised to receive NAC 200 mg kg(-1) over 20 min, the remaining group was given the same volume of vehicle. Blood samples drawn at time points 0 and 75 min were also studied in vitro and stimulated with LPS or LPS plus NAC. Selected physiologic variables and degree of organ injury were equal in both groups. TNF-alpha, IL-1beta, and reactive oxygen species (ROS) tended to be lower in the NAC-group (NS). In vitro, NAC significantly reduced the release of the same cytokines after the LPS challenge in blood drawn before injury. NAC did not influence post-traumatic endotoxin tolerance. Adding NAC to the immediate resuscitation fluid did not influence the early post-traumatic organ injury, and initiation of inflammatory responses significantly, or endotoxin tolerance. In vitro, NAC significantly reduced proinflammatory cytokine release, but only in normal blood. The clinical value of this treatment regimen is probably restricted, both due to the unfavourable post-traumatic internal environment and imposed dosing limitations.


Asunto(s)
Acetilcisteína/uso terapéutico , Resucitación , Heridas y Lesiones/terapia , Acetilcisteína/administración & dosificación , Animales , Endotoxinas/sangre , Inflamación/sangre , Inflamación/etiología , Interleucina-1/sangre , Leucocitos , Neutrófilos , Noruega , Especies Reactivas de Oxígeno/sangre , Porcinos , Factor de Necrosis Tumoral alfa/análisis , Heridas y Lesiones/sangre , Heridas y Lesiones/inmunología
10.
Tidsskr Nor Laegeforen ; 125(22): 3098-100, 2005 Nov 17.
Artículo en Noruego | MEDLINE | ID: mdl-16299563

RESUMEN

BACKGROUND: Brominated flame retardants are incorporated into an ever-increasing number of ordinary consumer goods, which has lead to pollution of the environment, wildlife, food of animal origin, and human blood, adipose tissue, and mother's milk. This group of chemicals has a striking structural similarity with the thyroid hormones and may constitute a potential health risk by interfering with thyroid hormone homeostasis. MATERIAL AND METHODS: We focus on these features and discuss possible clinical consequences, on the basis of Medline searches and our own experience. RESULTS: The thyroid hormones are essential for normal brain development. Disruption of the hormonal balance may lead to serious and permanent defects of neurological functioning. Brominated flame retardants may interfere with thyroid synthesis, transport, receptor binding, and elimination. The clinical consequences have so far not been firmly established, but results from animal studies suggest that even subtle disturbances of thyroid homeostasis during pregnancy may have serious implications for the developing brain. INTERPRETATION: Numerous scientific reports confirm the neurotoxic potential of these chemicals. The foetus and newborn are especially vulnerable.


Asunto(s)
Encéfalo/efectos de los fármacos , Contaminantes Ambientales/efectos adversos , Retardadores de Llama/efectos adversos , Bifenilos Polibrominados/efectos adversos , Animales , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Contaminantes Ambientales/farmacocinética , Contaminantes Ambientales/toxicidad , Femenino , Retardadores de Llama/farmacocinética , Retardadores de Llama/toxicidad , Humanos , Recién Nacido , Bifenilos Polibrominados/química , Bifenilos Polibrominados/farmacocinética , Bifenilos Polibrominados/toxicidad , Embarazo , Receptores de Hormona Tiroidea/efectos de los fármacos , Factores de Riesgo , Hormonas Tiroideas/metabolismo
11.
Resuscitation ; 58(1): 103-12, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12867316

RESUMEN

Accidental hypothermia is a common companion of trauma/haemorrhage, and several clinical studies have identified reduced body temperature as an independent risk predisposing to increased morbidity and mortality. Accordingly, the majority of trauma care guidelines prescribe early and aggressive rewarming of hypothermic patients. Enzyme reactions are generally downregulated at temperatures below 37 degrees C, including most of those responsible for the inflammatory response. The rationale for adhering to these recommendations uncritically may therefore be questioned. In a rat model of mild hypothermia and haemorrhagic shock we wanted to compare the influence of rapid rewarming with persistently reduced temperature on the synthesis of early inflammatory mediators and organ function. Thirty-four male albino Sprague-Dawley rats were studied. Withdrawal of 2.5 ml blood/100 g body weight was performed over 10 min, with simultaneous reduction of body temperature to 32.5-33.5 degrees C. Seventy-five minutes after initiation of bleeding, two-thirds of the shed blood was retransfused. One group (n=17) was rewarmed to normothermia, the other (n=17) was kept hypothermic. The study was terminated after an observation period of 2 h. At the end of the study the rewarmed animals had a significantly lower mean arterial pressure, higher heart rate, higher synthesis of reactive oxygen species from peritoneal phagocytes, increased circulating levels of nitric oxide, and higher values of the organ markers aspartate aminotransferase and urea. The pro-inflammatory cytokines TNF-alpha and IL-6, the anti-inflammatory cytokine IL-10, the organ markers alanine aminotransferase, alpha-glutathione S-transferase and creatinine, as well as organ injury scores were equal in both groups. Three rewarmed rats died prematurely, versus one hypothermic animal. In conclusion, the results suggest that during the early stages after haemorrhagic shock, rapid rewarming from mild hypothermia may have unfavourable effects both on basic haemodynamic variables, and on the internal inflammatory environment of cells and tissues.


Asunto(s)
Hipotermia/terapia , Inflamación/etiología , Recalentamiento/efectos adversos , Choque Hemorrágico/fisiopatología , Animales , Líquido Ascítico/citología , Hipotermia/complicaciones , Inflamación/sangre , Mediciones Luminiscentes , Masculino , Ratas , Ratas Sprague-Dawley , Choque Hemorrágico/complicaciones
12.
Neurochem Int ; 72: 30-6, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24726767

RESUMEN

The present study was designed to investigate the effects of long-term exposure (4 weeks) to the widely used narcotic drug and putative neurotoxicant 3,4-methylenedioxymetamphetamine (MDMA; "ecstasy") on neuronal transmitter transport and progression of experimental periodontitis in male Wistar rats. The rats were exposed to MDMA (10mg/kg/day i.p.) or saline five days a week for four consecutive weeks. Exposure to MDMA induced a significant reduction in the synaptosomal reuptake of serotonin, while the uptake of dopamine was significantly increased 24h after the last injection of MDMA. In contrast, the synaptosomal uptake of noradrenaline and the vesicular uptake through the vesicular monoamine transporter 2 were not affected. In the experiments of periodontitis development, ligature-induced periodontitis was induced three days prior to MDMA administration. Compared to controls, MDMA-treated rats developed significantly more periodontitis. In conclusion, our results show that long-term exposure to MDMA affects the serotonergic and dopaminergic transport systems in the rat brain and increased the susceptibility to the psychosomatic ailment periodontitis following disturbances of brain immune-regulatory systems. These results are interesting with respect to recent research showing that changes in neurotransmitter signalling may alter the reactivity of brain-controlled immunoregulatory systems controlling pathogenic microorganisms colonizing mucosal surfaces.


Asunto(s)
Química Encefálica/efectos de los fármacos , Encéfalo/inmunología , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Neurotransmisores/metabolismo , Periodontitis/patología , Serotoninérgicos/toxicidad , Pérdida de Hueso Alveolar/inducido químicamente , Pérdida de Hueso Alveolar/patología , Animales , Encéfalo/efectos de los fármacos , Progresión de la Enfermedad , Masculino , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacos
13.
Regul Pept ; 185: 14-9, 2013 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-23816467

RESUMEN

BACKGROUND: The classic chromogranin-secretogranin (granin) proteins are produced in the myocardium and throughout the neuroendocrine system, but while chromogranin (Cg) A and B levels are high in the adrenal medulla, secretogranin (Sg) II production is higher in the pituitary gland. Whether these differences may influence the response to physical activity is not known. METHODS: We measured circulating granin proteins during (1) a short-term maximal bicycle exercise stress test and (2) a 7 day military ranger course of continuous physical activity and sleep and energy deprivation. RESULTS: In 9 healthy subjects performing the exercise stress test (7 male, age 45±5 y [mean±SEM], duration 10.13±1.14 min), CgB levels increased from before to immediately after the test: 1.20±0.12 vs. 1.45±0.09 nmol/L, p=0.013. Metabolic equivalents, representing an index of performed work, were closely associated with the change (∆) in CgB levels during stress testing and explained 74% of the variability in ∆CgB levels (p=0.004). CgA and SgII levels were not increased after exercise stress testing. In the second cohort of 8 male subjects (age 25±1 y) participating in the ranger course, CgB levels increased from day 1 and were significantly elevated on days 5 and 7. CgA also increased gradually with levels significantly elevated on day 7, while SgII was markedly increased on day 5 whereas levels on days 3 and 7 were unchanged compared to baseline levels. CONCLUSION: We demonstrate a heterogeneous response to short- and long-term physical activities among circulating granin proteins with the most potent effect on CgB levels.


Asunto(s)
Cromogranina A/sangre , Cromogranina B/sangre , Esfuerzo Físico , Secretogranina II/sangre , Adulto , Ingestión de Energía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Privación de Sueño/sangre , Adulto Joven
14.
Open Dent J ; 5: 1-6, 2011 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-21339860

RESUMEN

BACKGROUND AND OBJECTIVE: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected. MATERIAL AND METHODS: Resiniferatoxin (RTX; 50 µg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 µg/kg i.p.) to induce a robust immune and stress response. RESULTS: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone. CONCLUSIONS: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways.

15.
Toxins (Basel) ; 2(1): 95-115, 2010 01.
Artículo en Inglés | MEDLINE | ID: mdl-22069549

RESUMEN

INFLAMMATORY MEDIATORS TRIGGER POLYMORPHONUCLEAR NEUTROPHILS (PMN) TO PRODUCE REACTIVE OXYGEN SPECIES (ROS: O(2) (-), H(2)O(2), ∙OH). Mediated by myeloperoxidase in PMN, HOCl is formed, detectable in a chemiluminescence (CL) assay. We have shown that the abundant cytosolic PMN protein calprotectin (S100A8/A9) similarly elicits CL in response to H(2)O(2) in a cell-free system. Myeloperoxidase and calprotectin worked synergistically. Calprotectin-induced CL increased, whereas myeloperoxidase-triggered CL decreased with pH > 7.5. Myeloperoxidase needed NaCl for CL, calprotectin did not. 4-hydroxybenzoic acid, binding ∙OH, almost abrogated calprotectin CL, but moderately increased myeloperoxidase activity. The combination of native calprotectin, or recombinant S100A8/A9 proteins, with NaOCl markedly enhanced CL. NaOCl may be the synergistic link between myeloperoxidase and calprotectin. Surprisingly- and unexplained- at higher concentration of S100A9 the stimulation vanished, suggesting a switch from pro-oxidant to anti-oxidant function. We propose that the ∙OH is predominant in ROS production by calprotectin, a function not described before.


Asunto(s)
Peroxidasa , Especies Reactivas de Oxígeno , Calgranulina B , Peróxido de Hidrógeno , Complejo de Antígeno L1 de Leucocito , Neutrófilos , Especies Reactivas de Oxígeno/metabolismo
16.
Eur J Appl Physiol ; 97(2): 151-7, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16506059

RESUMEN

Both exhaustive physical exertion and starvation have been reported to induce depression of immune function. The aim of the present study was to investigate the inflammatory environment and state of activation and mediator-producing potential of circulating leukocytes during prolonged physical activity with concomitant energy and sleep deprivation. Eight well-trained males were studied during 7 days of semi-continuous physical activity. Sleep was restricted to about 1 h/24 h, energy intake to 1.5- 3.0 MJ/24 h. Blood was drawn at 07.00 A.M.: on days 0, 2, 4, and 7. Plasma levels of inflammation markers were measured. The response of circulating leukocytes to lipopolysaccharide (LPS; 1 microg mL(-1)), and the effect of added hydrocortisone (10 and 100 nmol L(-1)), were measured in the supernatant after 3 h of incubation in an ex vivo whole blood model. Activation of leukocytes steadily increased as measured by plasma matrix metalloproteinase-9, tumour necrosis factor-alpha, interleukin-1beta, and interleukin-6. Inhibitors of systemic inflammation were either unaltered (tissue inhibitor of matrix metalloproteinase-1) or elevated (plasma interleukin-1 receptor antagonist). Cortisol levels increased on days 2 and 4, but thereafter reverted to baseline values. The leukocytes responded to LPS activation with increasing release of inflammatory cytokines throughout the study period. The anti-inflammatory potency of hydrocortisone decreased. Prolonged multifactorial stress thus activated circulating immune cells and primed them for an increased response to a subsequent microbial challenge.


Asunto(s)
Privación de Alimentos/fisiología , Leucocitos/metabolismo , Esfuerzo Físico/fisiología , Privación de Sueño/fisiopatología , Adulto , Peso Corporal/fisiología , Proteína C-Reactiva/análisis , Humanos , Hidrocortisona/farmacología , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Leptina/sangre , Recuento de Leucocitos , Leucocitos/citología , Leucocitos/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Sialoglicoproteínas/sangre , Privación de Sueño/sangre , Estrés Fisiológico/sangre , Estrés Fisiológico/fisiopatología , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/sangre , Factor de Necrosis Tumoral alfa/análisis
17.
J Periodontal Res ; 41(1): 23-32, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16409252

RESUMEN

OBJECTIVE: The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis has been found to play a significant role for susceptibility and resistance to periodontal disease. In the present study we have investigated the effects of two different treatment strategies, which have been found to down-regulate the HPA axis, on ligature-induced periodontitis. METHODS: In experiment 1, newborn rats were treated with the synthetic glucocorticoid hormone dexamethasone-21-phosphate, which permanently down-regulates HPA axis responsiveness. In experiment 2, adult rats were treated with the novel antidepressant drug tianeptine, which opposes the action of stress. Periodontitis was inflicted upon all rats. Just before decapitation the animals received gram-negative bacterial lipopolysaccharide (LPS) to induce a robust immune and HPA axis response. RESULTS: Compared to the saline-treated control rats, dexamethasone-treated rats had significantly less periodontal bone loss (p < 0.01), reduced expression of glucocorticoid receptors in the hippocampus (p < 0.001), lower corticosterone (p=0.01) and higher plasma levels of the cytokine tumor necrosis factor (TNF)-alpha (p < 0.05) after LPS challenge. Also the tianeptine-treated rats showed significantly reduced periodontal bone loss (p=0.01), enhanced plasma levels of TNF-alpha (p < 0.05), and transforming growth factor-1beta (p < 0.01), whereas no significant difference was found in corticosterone levels. CONCLUSION: An individual's responsiveness to danger signals, whether they are of immunological, chemical, or psychological origin, may be an important factor for explaining variability in susceptibility to periodontal disease. The results may provide new insight into the mechanisms of periodontal disease development, and open new vistas for disease prevention.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Periodontitis/prevención & control , Tiazepinas/uso terapéutico , Factores de Edad , Pérdida de Hueso Alveolar/prevención & control , Animales , Animales Recién Nacidos , Antiinflamatorios/administración & dosificación , Antidepresivos Tricíclicos/administración & dosificación , Dexametasona/administración & dosificación , Dexametasona/análogos & derivados , Susceptibilidad a Enfermedades , Regulación hacia Abajo , Glucocorticoides/administración & dosificación , Bacterias Gramnegativas/inmunología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/inmunología , Lipopolisacáridos/inmunología , Periodontitis/inmunología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/inmunología , Ratas , Ratas Wistar , Tiazepinas/administración & dosificación , Factor de Crecimiento Transformador beta/sangre , Factor de Crecimiento Transformador beta1 , Factor de Necrosis Tumoral alfa/análisis
18.
J Clin Periodontol ; 33(7): 469-77, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16820034

RESUMEN

OBJECTIVE: To test the hypothesis that the olfactory bulbectomy model of depression in rats could influence susceptibility to ligature-induced periodontitis, and that chronic treatment with the anti-depressant drug tianeptine could attenuate this effect. MATERIAL AND METHODS: Tianeptine was given twice daily (10 mg/kg, i.p.) during the entire experiment, starting 29 days before induction of olfactory bulbectomy and periodontitis. Olfactory bulbectomized (OB) rats and sham-operated rats were given saline in a similar manner. Periodontal disease was assessed when the ligatures had been in place for 21 days. Two hours before decapitation, rats were injected with lipopolysaccharide (LPS;100 microg/kg, i.p.) to induce a robust immune and stress response. RESULTS: Compared with sham-operated controls, OB rats developed significantly more periodontal bone loss, exhibited characteristic behavioural responses in a novel open field test, and showed a decreased expression of glucocorticoid receptors (GRs) in the hippocampus. LPS provoked a significantly larger increase in circulating levels of the stress hormone corticosterone and the cytokine transformation growth factor (TGF)-1beta but smaller tumour necrosis factor (TNF)-alpha levels. Tianeptine treatment of OB rats significantly inhibited peridodontal bone loss, normalized behavioural responses, enhanced TGF-1beta levels, and abolished TNF-alpha decrease, but did not attenuate the increased corticosterone response and the decreased hippocampal GR expression. CONCLUSIONS: These experimental results are consistent with an emerging literature showing that life stress, anxiety, depression, pathological grief, and poor coping behaviour may dysregulate regulatory mechanisms within the brain involved in immune regulation, and thereby alter immune responses and influence the susceptibility/resistance to inflammatory disorders.


Asunto(s)
Antidepresivos/uso terapéutico , Depresión/complicaciones , Bulbo Olfatorio/fisiología , Periodontitis/etiología , Tiazepinas/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/etiología , Análisis de Varianza , Animales , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Mediadores de Inflamación/sangre , Ligadura , Lipopolisacáridos/inmunología , Masculino , Inflamación Neurogénica/etiología , Neuroinmunomodulación , Bulbo Olfatorio/cirugía , Periodontitis/sangre , Periodontitis/tratamiento farmacológico , Periodontitis/inmunología , Ratas , Ratas Wistar , Estadísticas no Paramétricas
19.
J Periodontal Res ; 40(4): 325-30, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15966910

RESUMEN

OBJECTIVE: The responsiveness of the sympathetic nervous system (SNS) and the hypothalamic--pituitary--adrenal (HPA) axis plays a major role in immune regulation and for the outcome of infections and inflammatory disorders. This study was designed to investigate whether chemical SNS denervation with the noradrenaline-selective neurotoxic drug 6-hydroxydopamine (6-OHDA), which destroys peripheral noradrenaline terminals, would influence immune responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation, and the progression of ligature-induced periodontal disease in Fischer 344 rats. MATERIAL AND METHODS: 6-OHDA (40--60 microg/kg) or vehicle was injected intraperitoneally (i.p.) on days 1, 3 and 5, 10 days before application of the ligatures, and thereafter weekly in doses of 80 microg/kg. Periodontal disease was assessed when the ligatures had been in place for 49 days. At 24 and 2 h before decapitation, all rats received LPS (150 microg/kg i.p.) to induce a robust immune and HPA axis response. RESULTS: The 6-OHDA-treated rats showed significantly reduced bone loss as measured by digital X-rays (p< 0.01), and enhanced levels of the cytokines transforming growth factor-beta (p=0.05) and interleukin-6 (p=0.05), as well as the HPA axis derived hormone corticosterone (p=0.01), induced by LPS stimulation. CONCLUSIONS: 6-OHDA-induced chemical sympathectomy inhibits ligature-induced periodontal disease in this model. This effect may be attributable to the well-documented ability of the SNS to regulate immune system function primarily via the adrenergic neurotransmitter noradrenaline released at sympathetic nerve terminals. The enhanced HPA axis activation may be a compensatory response that reduces the T helper (Th)2 to Th1 skewing effect of treatment with 6-OHDA.


Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Enfermedades Periodontales/inmunología , Enfermedades Periodontales/metabolismo , Simpatectomía Química/métodos , Animales , Corticosterona/biosíntesis , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Inyecciones Intraperitoneales , Interleucina-10/biosíntesis , Interleucina-6/biosíntesis , Lipopolisacáridos , Masculino , Oxidopamina/administración & dosificación , Enfermedades Periodontales/etiología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Estadísticas no Paramétricas , Estrés Psicológico/complicaciones , Estrés Psicológico/inmunología , Simpaticolíticos/administración & dosificación , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis
20.
J Clin Periodontol ; 32(4): 347-52, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15811050

RESUMEN

OBJECTIVE: We have investigated whether a purified immunomodulatory water soluble beta-1,3/1,6-glucan isolated from the cell wall of Bakers yeast, Saccharomyces cerevisiae, would influence the progression of ligature-induced periodontal disease, and to modulate accompanying cytokine and hypothalamic-pituitary-adrenal (HPA) axis responses to a lipopolysaccharide (LPS) challenge. MATERIAL AND METHODS: beta-1,3/1,6-glucan (10 mg/kg/day) was given in the drinking water to Wistar rats during the entire experiment, starting 14 days before disease induction, while control rats were given tap water only. Periodontal disease was assessed when the ligatures had been in place for 35 days. RESULTS: Orally administered soluble beta-1,3/1,6-glucan significantly reduced periodontal bone loss as measured on digital X-rays (p=0,026). Glucan-treated rats also showed a significantly enhanced plasma level of the HPA axis-driven hormone corticosterone (p=0.047), and of the cytokine transforming growth factor-1beta (p=0.032), as well as a tendency to enhanced IL-10 (p=0.106), induced by intra-peritoneally administered LPS. CONCLUSION: Soluble beta-1,3/1,6-glucan administered by the oral route diminishes ligature-induced periodontal bone loss in this model. This effect may be attributable to the well documented ability of beta-1,3/1,6-glucan to stimulate macrophage phagocytosis and to skew the T helper (Th)1/Th2 balance towards Th1 and T regulatory responses. The HPA axis may play a significant role in beta-1,3/1,6-glucan induced immune modulation.


Asunto(s)
Glucanos/uso terapéutico , Enfermedades Periodontales/tratamiento farmacológico , beta-Glucanos/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/inmunología , Animales , Corticosterona/sangre , Sistema Hipotálamo-Hipofisario/fisiología , Interleucina-10/sangre , Ligadura , Lipopolisacáridos/administración & dosificación , Masculino , Enfermedades Periodontales/inmunología , Sistema Hipófiso-Suprarrenal/fisiología , Ratas , Ratas Wistar , Saccharomyces cerevisiae , Factor de Crecimiento Transformador beta/sangre , Factor de Crecimiento Transformador beta1 , Factor de Necrosis Tumoral alfa/análisis
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