Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. Copyright (C) 2011 S. Karger AG, Basel

Toll-like receptor 2/MyD88 signaling mediates zymosan-induced joint hypernociception in mice: Participation of TNF-alpha, IL-1 beta and CXCL1/KC

Arthritic pain is a serious health problem that affects a large number of patients. Toll-like receptors (TLRs) activation within the joints has been implicated in pathophysiology of arthritis. However, their role in the genesis of arthritic pain needs to be demonstrated. In the present study, it was addressed the participation of TLR2 and TLR4 and their adaptor molecule MyD88 in the genesis of joint hypernociception (a decrease in the nociceptive threshold) during zymosan-induced arthritis. Zymosan injected in the tibio-tarsal joint induced mechanical hypernociception in C57BL/6 wild type mice that was reduced in TLR2 and MyD88 null mice. On the other hand, zymosan-induced hypernociception was similar in C3H/HePas and C3H/Hej mice (TLR4 mutant mice). Zymosan-induced joint hypernociception was also reduced in TNFR1 null mice and in mice treated with IL-1 receptor antagonist or with an antagonist of CXCR1/2. Moreover, the joint production of TNF-alpha, IL-1 beta and CXCL1/KC by zymosan was dependent on TLR2/MyD88 signaling. Investigating the mechanisms by which TNF-alpha, IL-1 beta and CXCL1/KC mediate joint hypernociception, joint administration of these cytokines produced mechanical hypernociception, and they act in an interdependent manner. In last instance, their hypernociceptive effects were dependent on the production of hypernociceptive mediators, prostaglandins and sympathetic amines. These results indicate that in zymosan-induced experimental arthritis, TLR2/MyD88 is involved in the cascade of events of joint hypernociception through a mechanism dependent on cytokines and chemokines production. Thus, TLR2/MyD88 signaling might be a target for the development of novel drugs to control pain in arthritis. (C) 2011 Elsevier B.V. All rights reserved.

Isokinetic Strength and Endurance in Proximal and Distal Muscles in Patients With Peripheral Artery Disease

Background: The objective of this study was to analyze the muscle strength and endurance of the proximal and distal lower-extremity muscles in peripheral artery disease (PAD) patients. Methods: Twenty patients with bilateral PAD with symptoms of intermittent claudication and nine control subjects without PAD were included in the study, comprising 40 and 18 legs, respectively. All subjects performed an isokinetic muscle test to evaluate the muscle strength and endurance of the proximal (knee extension and knee flexion movements) and distal (plantar flexion and dorsiflexion movements) muscle groups in the lower extremity. Results: Compared with the control group, the PAD group presented lower muscle strength in knee flexion (-14.0%), dorsiflexion (-26.0%), and plantar flexion (-21.2%) movements (P < 0.05) but similar strength in knee extension movements (P > 0.05). The PAD patients presented a 13.5% lower knee flexion/extension strength ratio compared with the control subjects (P < 0.05), as well as lower muscle endurance in dorsiflexion (-28.1%) and plantar flexion (-17.0%) movements (P < 0.05). The muscle endurance in knee flexion and knee extension movements was similar between PAD patients and the control subjects (P > 0.05). Conclusion: PAD patients present lower proximal and distal muscle strength and lower distal muscle endurance than control patients. Therefore, interventions to improve muscle strength and endurance should be prescribed for PAD patients.

Assessing joint effusion and bone changes of the head of the mandible in MR images of symptomatic patients

The aim of the present study was to investigate the relationship between degenerative bone changes of the head of the mandible and the presence of joint effusion (JE). This study was based on sagittal magnetic resonance imaging (MRI) reports of 148 temporomandibular joints (TMJs) of 74 patients complaining of pain and/or dysfunction in the TMJ area. The mandible heads were surveyed for osteoarthritis characteristics, which were classified as osteophytosis, sclerosis or erosion. The presence of JE was checked whenever high signal intensity was observed in the articular space. The results evidenced the presence of bone changes in 30% of the sample. Osteophytes and erosions were the changes most commonly observed. JE was reported in 10% of TMJs. The results from the statistical tests revealed that bone changes in the head of the mandible are associated with the presence of JE.

Bilateral asymptomatic fibrous-ankylosis of the temporomandibular joint associated with rheumatoid arthritis: a case report

The American Academy of Orofacial Pain (AAOP) defines ankylosis of the temporomandibular joint (TMJ) as a restriction of movements due to intracapsular fibrous adhesions, fibrous changes in capsular ligaments (fibrous-ankylosis) and osseous mass formation resulting in the fusion of the articular components (osseous-ankylosis). The clinical features of the fibrous-ankylosis are severely limited mouth-opening capacity (limited range of motion during the opening), usually no pain and no joint sounds, marked deflection to the affected side and marked limitation of movement to the contralateral side. A variety of factors may cause TMJ ankylosis, such as trauma, local and systemic inflammatory conditions, neoplasms and TMJ infection. Rheumatoid arthritis (RA) is one of the systemic inflammatory conditions that affect the TMJ and can cause ankylosis. The aim of this study is to present a case of a female patient diagnosed with bilateral asymptomatic fibrous-ankylosis of the TMJ associated with asymptomatic rheumatoid arthritis. This case illustrates the importance of a comprehensive clinical examination and correct diagnosis of an unusual condition causing severe mouth opening limitation.

Estudo da anatomia do nervo tibial e seus ramos ao nível do terço distal da perna

OBJETIVO: Determinar, através de dissecção em cadáveres frescos, a anatomia topográfica do nervo tibial e seus ramos ao nível do tornozelo, em relação ao túnel do tarso. MÉTODOS: Foram realizadas dissecções bilaterais em 26 cadáveres frescos e as localizações da bifurcação do nervo tibial e seus ramos aferidas em milímetros, com relação ao eixo maleolar-calcaneal (EMC). Para os ramos calcâneos, a quantidade e seus respectivos nervos de origens também foram analisados. RESULTADOS: A bifurcação do nervo tibial ocorreu sob o túnel em 88% dos casos e proximalmente em 12%. Quanto aos ramos calcâneos, o medial apresentou-se com um (58%), dois (34%) e três (8%) ramos, com a origem mais comum do nervo tibial (90%) e o inferior com ramo único por perna, tendo o nervo plantar lateral como origem mais comum (70%). Nivel de Evidência V, Opinião de especialista.

Anxiety and joint hypermobility association: a systematic review

BACKGROUND: Anxiety disorders are often associated with several non-psychiatric medical conditions. Among the clinical conditions found in association with anxiety stands out the joint hypermobility (JH). OBJECTIVES: To carry out a systematic review of the clinical association between anxiety disorders and JH. METHOD: A survey was conducted in MEDLINE, PsychINFO, LILACS e SciELO databases up to December 2011. We searched for articles using the keywords 'anxiety', 'joint' and 'hypermobility' and Boolean operators. The review included articles describing empirical studies on the association between JH and anxiety. The reference lists of selected articles were systematically hand-searched for other publications relevant to the review. RESULTS: Seventeen articles were included in the analysis and classified to better extract data. We found heterogeneity between the studies relate to the methodology used. Most of the studies found an association between anxiety features and JH. Panic disorder/agoraphobia was the anxiety disorder associated with JH in several studies. Etiological explanation of the relationship between anxiety and JH is still controversial. CONCLUSION: Future research in large samples from the community and clinical setting and longitudinal studies of the association between anxiety and HA and the underlying biological mechanisms involved in this association are welcome.

Three new species of Lebiasina (Characiformes: Lebiasinidae) from the Brazilian shield border at Serra do Cachimbo, Pará, Brazil

Lebiasina marilynae n. sp., L. melanoguttata n. sp., and L. minuta n. sp. are described from the headwaters of the rio Curuá, in Serra do Cachimbo, Pará, Brazil, and represent the only members of the Lebiasininae in the Brazilian Shied, so far. A close relationship among these species is proposed based on: 1) the presence of a pair of foramina through which the ramus palatinus of the facial nerve passes, a modification unique in Lebiasinidae and apparently in the Characiformes, 2) the enlargement of the extrascapular bone, 3) the absence of the secondary stripe, and 4) the nearly equal length of caudal-fin lobes. Lebiasina marilynae additionally differs from all congeners in having the primary stripe extending from the tip of the snout to the distal border of the caudal-fin peduncle, the possession of two series of dark blotches parallel to the primary stripe, and a rounded dorsal surface of the mesethmoid. Lebiasina melanoguttata and Lebiasina minuta additionally differ from all congeners in the absence of the primary stripe and the caudal blotch, and the presence of three longitudinal series of dark blotches at the base of the scales of series 3-5. Lebiasina melanoguttata differs from Lebiasina minuta in the absence of a dark blotch at the base of the median rays of the dorsal fin, second infrapharyngobranchial bearing conical teeth, the reddish overall coloration of the eye and fins, and the dark blotches never coalescing (vs. dark dorsal-fin blotch present; the second infrapharyngobranchial being edentulous; dark, olive green eyes, and the yellowish overall color of body and fins; and the dark blotches of longitudinal series 3 and 4 coalescing where scales of adjacent longitudinal series overlap). The occurrence of species of the Lebiasininae on the Brazilian Shield is discussed, and the distribution pattern of the species described herein is compared to that of other endemic species of the Serra do Cachimbo, a highly biodiverse area isolated from the rest of the Amazon basin.

Liberalism, Marxism and Democratic Theory Revisited: Proposal of a Joint Index of Political and Economic Democracy

Liberalism and Marxism are two schools of thought which have left deep imprints in sociological, political and economic theory. They are usually perceived as opposite, rival approaches. In the field of democracy there is a seemingly insurmountable rift around the question of political versus economic democracy. Liberals emphasize the former, Marxists the latter. Liberals say that economic democracy is too abstract and fuzzy a concept, therefore one should concentrate on the workings of an objective political democracy. Marxists insist that political democracy without economic democracy is insufficient. The article argues that both propositions are valid and not mutually exclusive. It proposes the creation of an operational, quantifiable index of economic democracy that can be used alongside the already existing indexes of political democracy. By using these two indexes jointly, political and economic democracy can be objectively evaluated. Thus, the requirements of both camps are met and maybe a more dialogical approach to democracy can be reached in the debate between liberals and Marxists. The joint index is used to evaluate the levels of economic and political democracy in the transition countries of Eastern Europe.

The regulation of NHE₁ and NHE₃ activity by angiotensin II is mediated by the activation of the angiotensin II type I receptor/phospholipase C/calcium/calmodulin pathway in distal nephron cells

Angiotensin II (Ang II), acting via the AT1 receptor, induces an increase in intracellular calcium [Ca(2+)]i that then interacts with calmodulin (CaM). The Ca(2+)/CaM complex directly or indirectly activates sodium hydrogen exchanger 1 (NHE1) and phosphorylates calmodulin kinase II (CaMKII), which then regulates sodium hydrogen exchanger 3 (NHE3) activity. In this study, we investigated the cellular signaling pathways responsible for Ang II-mediated regulation of NHE1 and NHE3 in Madin-Darby canine kidney (MDCK) cells. The NHE1- and NHE3-dependent pHi recovery rates were evaluated by fluorescence microscopy using the fluorescent probe BCECF/AM, messenger RNA was evaluated with the reverse transcription polymerase chain reaction (RT-PCR), and protein expression was evaluated by immunoblot. We demonstrated that treatment with Ang II (1pM or 1 nM) for 30 min induced, via the AT1 but not the AT2 receptor, an equal increase in NHE1 and NHE3 activity that was reduced by the specific inhibitors HOE 694 and S3226, respectively. Ang II (1 nM) did not change the total expression of NHE1, NHE3 or calmodulin, but it induced CaMKII, cRaf-1, Erk1/2 and p90(RSK) phosphorylation. The stimulatory effects of Ang II (1 nM) on NHE1 or NHE3 activity or protein abundance was reduced by ophiobolin-A (CaM inhibitor), KN93 (CaMKII inhibitor) or PD98059 (Mek inhibitor). These results indicate that after 30 min, Ang II treatment may activate G protein-dependent pathways, including the AT1/PLC/Ca(2+)/CaM pathway, which induces CaMKII phosphorylation to stimulate NHE3 and induces cRaf-1/Mek/Erk1/2/p90(RSK) activity to stimulate NHE1