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Obiectiv: Studiul in vivo a reactivita?ii cailor respiratorii in astmul alergic indus prin expunerea la ovalbumina, prin monitorizarea PEIP (presiunea pozitiva tele-inspiratorie) la sobolanul anesteziat si ventilat mecanic, urmat de evaluarea in vitro a reactivitatii musculaturii traheale. Aim: The present study was purported to determine the value and applicability of positive end-inspiratory pressure (PEIP) for the in vivo assessment of airways responsiveness (AR) in an experimental model of asthma induced in rats by ovalbumin (OVA) sensitization. Rodents develop AHR to several broncho-constrictors after systemic and local allergen sensitization followed by allergen challenge via the airways.
The most commonly employed experimental models for studying AHR are using an in vitro approach, namely organ bath studies of isolated tracheal strips harvested from the sensitized animals. The primary objective of the present study was to evaluate the applicability of positive end-inspiratory pressure (PEIP) measurement as a valid indicator for the in vivo assessment of airway hyperreactivity in a well-established model of allergic asthma in rats. In vivo experiments in rodents require an adequate anesthesia and ventilation. Pancuronium bromide (Pavulon 2 mg i.v), a nondepolarizing blocker of acetylcholine action at the motor end-plate of neuromuscular junction was also administered. After local anesthesia of hipopharynx, epiglottis and glottis with xyline 4%, animals were intubated by means of a custom-made laryngoscope.4 (Fig.
The left common carotid artery was dissected free for the insertion of a fluid-filled catheter connected to a pressure transducer (APT 300 Hugo Sachs Elektronik-Harvard Apparatus GmbH) to monitor arterial blood pressure and to allow blood sampling for acide-base status assessment. The right jugular vein was cannulated for administration of crystalloid solutions for fluid repletion to compensate for blood, NaHCO3 sol. Rectal temperature was recorded via a precalibrated steel thermistor probe and core temperature was maintained at 37-38A°C with the aid of a heating pad.
Spirally cut tracheal strips were suspended in an organ bath, and one end was fixed to the bottom of the bath while the other was connected to an isometric force transducer (FORT 10, World Precision Instruments, WPI Inc). Strips were pretensioned (1.5 g), allowed to equilibrate for 60-90 minutes and washed every 15 minutes with Krebs-Henseleit solution before the isometric tension was recorded. Contractile response of tracheal strips to a submaximal dose of MCh (10-5M) harvested from the OVA group were compared with those from the CON group. Ovalbumin is the most used allergen in experimental models of allergic bronchial asthma on rats.
Several methods for the in vivo as sessment of airway responsiveness and of bronchconstriction in laboratory animals are reported in the literature.
In our model we used for anesthesia sodium pentothal with no reported effects on respiratory airways. Experimental animal models represent the first research step in the attempt to describe pathophysiology of a disease, in this case, allergic asthma. In the rat model of ovalbumin induced-asthma, positive end-inspiratory pressure is a valid index of airways hyperreactivity as confirmed by the comparable results obtained in isolated organ bath. Obiective: Evaluarea comparativa a efectului lui Der p 1, componenta alergenica majora a acarianului prezent in praful de casa, Dermatophagoides pteronyssinus (Der p), asupra productiei de cytokine de tip Th2 de catre celulele dendritice diferentiate din monocite provenite de la pacienti alergici la praful de casa si de la subiecti sanatosi.
Objective: To evaluate the effect of Der p 1, the major allergen of the house dust mite Dermatophagoides pteronyssinus (Der p), on Th2 cytokines production in coculture of naA?ve T cells and monocyte-derived DCs from Der p allergic patients and healthy donors.
Allergic diseases are inflammatory disorders characterized especially by accumulation of eosinophils, T cells and mast cell. The physiologic role of DCs is to perform a continuous survey of the antigen-exposed sites of the body, and to orientate the response to a certain antigen towards an immunogenic or a tolerogenic pathway. Differentiation into Th1 or Th2 response depends on many factors like : the nature and the dose of the antigen, the route of exposure, the genetic background of the individual, the type of costimulatory molecules expressed on the surface of the DCs, the polarizing cytokines microenvironment during antigen presentation. Depending on their origin and their capacity to induce preferentially, the differentiation of naive T cells into Th1 and Th2 effectors cells, there were described two subclasses of DCs - DC1 and DC2. It was shown also that the type of costimulatory molecules expressed on the DCs surface is essential for determining Th differentiation. The orientation toward Th1 or Th2 profile is also dependent on the prevalence of IL-10 or IL-12 secreted by DCs, as polarizing cytokines during the DCs - T cells interaction. The aim of the study was to evaluate the comparative effect of Der p1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus (Der p), and LPS - the major component of the outer membrane of Gram-negative bacteria, on monocyte-derived DCs obtained from patients sensitive to Der p and from healthy donors. Allergic patients suffered for allergic rhinitis A± allergic asthma defined according to ARIA criteria and GINA criteria, respectively11,12.
Peripheral venous blood was collected from house dust mite allergic patients (n = 8) and healthy donors (n = 7). Supernatants of DCs pulsed or not with Der p 1 or LPS were harvested after 24 hours and assayed for the presence of IL-10, and IL-12 by specific enzyme-linked immunosorbent assay (ELISA) using Eli-pairs (R&D Systems). NaA?ve CD4+ T cells were isolated by depletion of non-T helper cells and memory CD4+ T cells from PBMCs, using an indirect magnetic labelling system with a cocktail of biotin-conjugated monoclonal antibodies (Miltenyi Biotec). Generated DCs from allergic patients or from healthy donors previously pulsed or not with Der p 1 or LPS for 24 hours were cocultured with the autologous naive CD4+ T cells (ratio 1:10). Statistical analysis of DC surface markers and cytokine production were performed using Student t test.
We analyzed the expression of DC markers CD1a, CD11c and HLA-DR and the costimulatory molecules CD80, CD86 and CD83. Der p 1 exposure induced an up-regulates CD80 expression on DCs in healthy donors and CD86 and CD83 expression on DCs in house dust mite allergic patients.
Pulsed DCs have an intense capacity to induce the in vitro autologous T-cells proliferation. IL-10 and IL-12 are known to play a very important role in the orientation of the immune modulation and because of that it was evaluated theirs production as a DCs response at antigen pulsation.
It is known that the orientation of immune response depends on multiple factors, DCs being considered to play a key role in the initiation of primary immune response and in the amplification of secondary immune response. Expression of CD83, a maturation marker of PBMC-derived-DC, is visible lower on Der p 1-pulsed DCs comparatively with LPS-pulsed DCs. The modulation of immune response into a Th1 or Th2 type depends on microenvironment cytokines present during the interaction between DCs and naive T cells, specially IL-10 and IL-12, both produced by DCs.
In response to Der p 1 stimulation, DCs from allergic patients induce on autologous T cells an increased IL-4 production comparison with IFN-I? production. All these data lead to the conclusion that the modulation of immune response and the establishment of the balance between allergy and tolerance against an allergen are close dependent on immune status of the individual. This "plain-talk" guide is intended to help you learn about your jaw joints and how to keep them healthy.
Over the following pages, you will read a lot about your jaw joints or, as they are more accurately called, your Temporomandibular Joints. In the absence of consensus within the health care community on this multi-faceted health disorder, this guide can help you to become involved in your own wellness. TMJ, stands for Temporomandibular joints and the physical disorders associated with these joints. TM Joints are separated into distinct cavities, cushioned by a disk of dense fibrous cartilage, held together by ligaments, and moved by many pairs of muscles.
Although health has become the leading topic in America and health programs abound, it is also a fact that we are not routinely taught how our bodies are structured, how one part of our body system interacts with another, and how we function.
Grinding your teeth or clenching of your jaws are often cited as the primary causes of TMJ. During cold weather, wear a hat and gloves to retain body heat and prevent the tensing and clenching that accompany feeling cold. When yawning, most people for politeness cover their mouth with their hand placed horizontally. Always use your seat belt to reduce whiplash and resulting head or neck injury, and wear your helmet while biking or skating. Question ads and doctors that promise to improve your appearance without explaining the possible long-term adverse side effects of the treatments offered. For healthy babies, the first trimester is critical to the cranial-facial complex development-so avoid smoking, alcohol, and drugs and eat a very nutritious diet when pregnant. If you have any of these symptoms, your primary care physician or dentist should be consulted.
Correct diagnosis is the first step to effective treatment, so it is essential to secure at least two independent opinions before any therapy begins. All treatments and exercise programs are intended to help you by strengthening the muscles, improving range of motion, or promoting relaxation for general well-being.


Current treatments vary greatly and may be self-administered or provided by a professional.
Plastic bite planes (splints) are often used on a short-term basis to reposition the jaw joints, relax the muscles, and reduce the pressure on the teeth and joints.
Any non-invasive treatment which helps to stop the pain and improve function is preferable. Women routinely seek medical and dental help more often than men; consequently, TMJ is seen more often in women and has become unfairly stereotyped. Work with your doctor to create a specific treatment plan, along with a cost and payment schedule. Be assertive in your treatment-ask questions about treatment alternatives and adverse side effects. Take very seriously any trauma to the head or neck or whiplash from vehicular, work, sports, or play accidents, regardless of your age or sex. Learn how pain and dysfunction can be released by hands-on therapy or by self-administered massage of the trigger points, acupressure points, or by application of ice or heat. Be aware that non-surgical TMJ treatments are usually expensive and often not covered by health insurance, whereby surgery is almost always covered-leading to choices that are based on economics rather than medical necessity.
Appropriate exercise, including a customized program of exercise for the jaw joints, can improve range of motion, circulation, and strength. Contact community agencies such as your local library, United Way, State Clearing Houses, National Institutes of Health (NIH) or the Arthritis Foundation. The Arthritis Foundation and its publication, Arthritis Today, have not covered the subject of jaw joints or the TMJ disorder in depth to date. Read newsletters from other organizations who deal with similar health problems which overlap with TMJ (send a SASE for a list from JJAMD). First, physicians would become more involved in the prevention, diagnosis, and treatment of TMJ. The current focus on health care reform places on all of us the additional responsibility for consistent preventive education which will help to reduce the high cost associated with TMJ treatment.
All of the problems cited create what JJAMD calls "The TMJ Dilemma." It is JJAMD's mission to help overcome these problems and the burdens they place on both individuals and society. JJAMD has initiated a National TMJ Alliance to self-help support advocacy organizations and tie together a national program of information sharing and education about Temporomandibular joints.
JJAMD members network with other TMJ patients, learn from others' experience, gain emotional support, and learn about resources such as local self-help support groups (although there are only a few). For further information on Jaw joints and the TMJ Dilemma, please send a 9xl2 self-addressed stamped envelope to JJAMD Foundation, 790 Boylston Street, Suite 17G, Boston, MA 02199. Please complete JJAMD's own Research Questionnaire in the Survey portion of this web-site and return for inclusion to our database and for ongoing research. There are a variety of names, acronyms, diagnoses, and treatments-too many to list all or the detailed definitions herein. Terminology in some cases has become charged with meanings that sometimes work to the disadvantage of the TMJ patient. Other Names Used for TMJ Disorder-Temporomandibular Disorder, Craniofacial Pain, Maxillofacial Pain, Orofacial Pain, Myofascial Pain Dysfunction and others. More and more, patients and advocacy organizations are reporting on a variety of similar problems, signs and symptoms, and other disorders, that overlap with their jaw joints.
Sponsored by the Jaw Joints & Allied Musculo-Skeletal Disorders Foundation, Inc - (JJAMD), a 501 (c) (3) educational advocacy organization, est.
Material si metode: Studiul s-a efectuat pe 2 loturi de sobolan Spague-Dawley, de sex M, dintre care un lot a fost de control (CON, n = 8) si un lot sensibilizat la ovalbumina (OVA, n = 8). One of the largely used allergen is ovalbumin, and several protocols of sensitization have been used in inducing experimental models of asthma as summarized in Table 1.
The presence of AHR was further confirmed by the in vitro evaluation of tracheal smooth muscle reactivity in isolated organ bath. All investigations conformed to the Guide for the Care and Use of Laboratory Animals (US National Institute of Health no. Anesthesia inhibits respiratory musculature causing a shortage of oxygen and accumulation of carbon dioxide, thus leading to acidosis and eventually death. Ventilatory parameters were continuously adjusted according to arterial blood gases and acide-base parameters (AVL 995 blood gas analyzer).
In order to perform reproducible experiments, the contractile response of tracheal strips using acetylcholine (10-5 M) was assessed and only strips with two similar contractions were further studied. After every step of experiment the strips were washed with Krebs-Henseleit solution, 3 times, at 1-2 minutes interval and a 5-10 minutes period for the recovery of basal tone was allowed.
However, asthma in rodents might not present with all the characteristics of human disease, since the large majority models (including ours) of experimental induced asthma evaluate the acute response after a short period of exposure to allergen.
We propose the determination of this parameter as a physiologically valid measure of in vivo airway hyperresponsiveness in allergic rodents.
Inhibition of phosphodiesterase-4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. Material si metode: Din sangele venos periferic al pacientilor inclusi in studiu am izolat monocite, din care am diferentiat celule dendritice utilizand GM-CSF si IL-4. Material and methods: CD14+ monocytes were isolated from venous peripheral blood and differentiated to DCs using GM-CSF and IL-4.
The inflammation is controlled by T-helper type 2 cells (Th2) secreting cytokines such as interleukin IL-4, IL-5, and IL-13, which orchestrate key features of allergy. Any inaccuracy in their function can lead either to a misbalanced immune defense response or to allergy, even the development of autoimmunity.1,2 DCs play an important role in the pathogenesis of allergic disorders through their ability to interact with T cells, which lead to initiation and amplification of Th 2 immune responses. The role of CD86 molecule seems to be more important than CD80 in allergic diseases development, based on its ability to induce the Th2 response. After platelet-rich plasma depletion, blood cells were diluted in RPMI 1640 (Promocell) and layered over a Ficoll gradient. They were incubated for 15 minutes with different monoclonal antibodies (mAbs): anti-CD14, anti-HLA-DR, anti-CD83, anti-CD80, anti-CD86, anti-CD1a (BD Biosciences). After 24 or 48 hours of coculture, supernatants were harvested and assayed for IL-4 and IFN-I? production using a specific ELISA (R&D Systems). Immature DCs, obtained after 7 days of culture, had the same characteristics in both healthy donors and allergic patients: high expression of CD1a and CD11c, and low expression of HLA-DR. T-cells proliferative response induced by Der p 1-pulsed DCs, represented as filled histogram (57.08%) vs.
T-cells proliferative response induced by LPS-pulsed DCs, represented as filled histogram (75.80%) vs.
IL-4 and IFN-I? production by autologous T cells stimulated with Der p 1-pulsed DCs from allergic patients and healthy donors. This demonstrates that LPS has a higher capacity to induce DC maturation when compared with the major allergen Der p 1. The main roles of IL-10 are the limitation of inflammatory response through down-regulation of Th1 proinflammatory cytokine expression (IFN-I?, IL-2, IL-6, IL-8, IL-12, and TNF- I±) and the stimulation of B-lymphocytes proliferation and diferentiation.17 Therefore, IL-10 is a Th2 response promoter. In DCs from healthy donors the same type of stimulation up-regulate IFN-I? production, orientated the response toward a Th1 response. Allergic response characterized through a high IL-10 production could be orchestrated by a DCs dysregulation. Jaw joints are also the essential path for the large neurological system running between the brain and the spinal cord, affecting all sensory and motor activity.
Therefore, we are often left to think that we can do anything we want to do with our bodies, without realizing that we can cause harm to ourselves through lack of understanding. 85-23, revised 1996) and were approved by the Ethics and Deontology Committee of our university.
3) A standard limb lead II electrocardiogram (ECG) was recorded from subcutaneous limb leads. Since no changes of ventilatory parameters (set in beginning of experiment) we postulate that PEIP strictly depends on pulmonary compliance or pneumatic resistance of respiratory airways. Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in allergic rats.


Antigen challenge of sensitized rats increases airway responsiveness to methacholine.
Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness. Temporal association between airway hyper-responsiveness and airway eosinophilia in ovalbumin-sensitized mice. Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodeling. Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice.
Dysfunction of muscarinic M2 receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea-pigs.
Repeated antigenic challenge-induced airway hyperresponsiveness and airway inflammation in actively sensitized rats. Concurrent dual allergen exposure and its effects on airway hyperresponsiveness, inflammation and remodeling in mice. The absence of Interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity. Manipulation of allergen-induced airway remodeling by treatment with anti-TGF-antibody: Effect on the smad signaling pathway. Bronchoconstriction and airway hyperresponsiveness after ovalbumin inhalation in sensitized mice.
The Efficacy of immunotherapy in an experimental murine model of allergic asthma is related to the strength and site of T cell activation during immunotherapy. Airway subepithelial fibrosis in a murine model of atopic asthma suppression by dexamethasone or antia€“Interleukin-5 antibody. Celulele dendritice izolate au fost stimulate cu Der p 1 sau LPS, utilizat ca si control al maturarii acestora.
The role of individual chemokines and chemokine receptors in the pathogenesis of allergic inflammation is often uncertain. Due to their location, immediately above the basement membrane of the airways epithelium, DCs have direct contact with incoming antigens.2 Mucosal DCs are immature DCs, with high endocytic and antigen processing activity and a weak capability to activate T-cells. Our results showed an IL-10 intense production after Der p 1 pulsation in allergic patients, thus developing a Th2 response.
A study showed that the level of IFN-I? was low and did not significantly differ between the two groups15. In the future, the new strategies for allergic diseases therapies should be focused on the essential role of DCs played in the establishment of the immune profile. Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge. Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma. Myeloid dendritic cells induce Th2 responses to inhaledantigen, leading to eosinophilic airway inflammation.
Alteration of balance between myeloid dendritic cells and plasmacytoid dendritic cells in peripheral blood of patients with asthma.
Immunocytochemical detection of cytokines and chemokines in Langerhans cells and in vitro derived dendritic cells. Differential role of CD80 and CD86 on alveolar macrophages in the presentation of allergen to T lymphocytes in asthma. Increased expression of CD86 and reduced production of IL-12 and L-10 by monocyte-derived dendritic cells from allergic asthmatics and their effects on Th1- and Th2-type cytokine balance. Kinetics of dendritic cell activation: impact on priming of Th1, Th2 and nonpolarized T cells.
Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response. A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-I? treatment. Reduced production of IL-12 and IL-12-dependent IFN-I? release by allergic asthma patients. JJAMD wishes to thank Ann George, Laura Ward, Phil Golden, and Susan Pearlman for their efforts in producing this guide, and Lew Sayre Schwartz for his cartoon illustrations. The rats were killed at the end of the experiments by an overdose of intravenous sodium pentobarbital. After antigen uptake, they lose their capacity to take up further antigens, they become mature DCs, and carry processed antigen from nonlymphoid tissues to the draining lymph nodes, where they become able to stimulate naive T cells.
4) When compared T-cells proliferate response induced by Der p 1-pulsed DCs from allergic patients, it was higher than the one observed healthy donors. The low expression of CD80 in healthy donors showed a close association between this costimulatory molecule and Th1 response modulation. In contrast, pulsation with LPS induced down-regulation of IL-10 production and increased amounts of IL-12 synthesis. Alergic rhinitis and its impact on asthma (ARIA) 2008 update (in colaboration with the World Health Organization, GA2LEN and AllerGen).
Accordingly, in the case of bronchoconstriction, the pneumatic resistance of respiratory airways will increase together with a proportional, correspondent increase of PEIP.
Celulele dendritice stimulate au fost co-cultivate impreuna cu limfocite T CD4+ naive autologe, iar in supernatantul de cultura s-a analizat prezenta IL-4 si a IFN-I?. Pulsed DCs were cocultured with autologous naive CD4+ T cells and the supernatant was assayed for IL-4 and IFN-I?. The healthy donors were non-allergic and non-asthmatic, with normal lung function and no history of respiratory diseases. 1) However, CD83 expression was visible lower on Der p 1-pulsed DCs when compared with LPS-pulsed DCs. Another study, performed by Xue-Qin C (2006) on patients with allergic asthma had the same results on CD86 expression.
We have further determined the in vitro reactivity of tracheal smooth muscle (spiral strips) challenged with a submaximal dose of MCh (10-5 M) in isolated organ bath.
Evaluarea in vitro a cailor respiratorii: am evaluat reactivitatea musculaturii netede traheale, pe preparate de tip spirala, la doza submaximala 10-5M MCh administrata in baia de organ izolat. Their study reported that M-DC from allergic patients pulsed with Der p 1 produced low levels of IL-10, whereas M-DC from healthy donors secreted significantly higher amounts of IL-10. Concerning P-DC, the incubation with Der p 1 induced low IL-10 production in both groups.18 Mosca (2000) demonstrated that IL-12 is a T cells stimulatory factor involved in Th1 differentiation of naive T cells. Concluzii: Expresia markerilor de suprafata a celulelor dendritice este diferit indusa de catre Der p 1 a€“ CD86 si CD83 la pacientii alergici, respectiv CD80 la subiectii sanatosi. Conclusions: Der p 1 up-regulates different surface markers expression on DCs - CD86 and CD83 in allergic patients, and CD80 in healthy donors.
Conclusions: In the rat model of allergic asthma, positive end-inspiratory pressure is a valid index of in vivo airways hyperreactivity as confirmed by the comparable results obtained in isolated organ bath. Limfocitele T naive stimulate de catre celulele dendritice pulsate cu Der p 1 produc cantitati mai mari de IL-4 comparativ cu cele de la pacientii sanatosi.
Autologous naive T cells from allergic patients in coculture with Der p 1-pulsed DCs induced higher IL-4 production than in healthy donors. We propose the determination of this parameter as a physiologically valid measure of airway hyperresponsiveness in allergic rodents.
Modularea raspunsului imun si definirea balantei intre alergia si toleranta sunt strans dependente de statusul imun individual. The modulation of immune response and the establishment of the balance between allergy and tolerance against an allergen are close dependent on the immune status of the individual.
Propunem utilizarea PEIP, ca fiind un parametru fiziologic valid, pentru pentru studiul hiperreactivitatii cailor aerifere din astmul alergic la sobolan.



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