The role of toll-like receptors in the adrenal gland

Sepsis is caused by infection and often followed by an overwhelming inflammatory response. This can lead to shock, organ failure and even death. Each year approximately 60,000 people die in Germany due to sepsis. There is good evidence that sepsis is associated with failure of the hypothalamic-pituitary-adrenal-axis. In patients with sepsis, glucocorticoids (e.g. corticosterone, cortisol) released from adrenal glands play an essential role in preventing an excessive pro-inflammatory response. Adrenal insufficiency occurs in a large number of patients with septic shock and is associated with an increased mortality. In the innate immune system, Toll-like receptors (TLRs) play a crucial role in its onset by recognizing pathogenassociated molecules. It is well known that there are interactions between the immune and endocrine stress systems; glucocorticoids and TLRs regulate each other in a bi-directional way. Therefore, a coordinated response of the adrenal and immune system is of vital importance for survival during severe inflammation. This experimental study focuses on the role of TLR-2, TLR-4 and TLR-9 during adrenal stress. The results show that in mice, the absence of TLR-2 and TLR-4, but not TLR-9 leads to altered adrenal morphology, relating to size and cellular structure. However, this alteration does not appear to compromise the phenotype of TLR knock-out mice. Mice deficient of TLR-2, 4 and 9 are not able to respond adequately to inflammatory stress induced by their potential ligands lipopolysaccharide (LPS), lipoteichoic acid (LTA) or cytidine phosphate guanosine-oligodeoxynucleotides (CpG-ODN). This impaired adrenal stress response appears to be associated with a decrease in systemic and intra-adrenal cytokine expressions. Taken together, these results suggest that TLR-2, 4 and 9 are key players in the immuno-endocrine response during inflammation and SIRS. In conclusion, TLRs play a crucial role in the immune-adrenal crosstalk. This close functional relationship needs to be considered in the treatment of inflammatory diseases where an intact adrenal stress response is required. Furthermore, TLR polymorphisms could contribute to the underlying mechanisms of impaired adrenal stress response in patients with bacterial sepsisSepsis entsteht durch eine Infektion, der oft eine unkontrollierte Entzündungsreaktion folgt und die letztendlich in Schock, Organversagen oder Tod münden kann. Jedes Jahr sterben allein in Deutschland bis zu 60.000 Menschen an einer Sepsis. Vieles weist darauf hin, dass die Sepsis in Zusammenhang mit dem Versagen der Hypothalamus-Hypophysen-Nebennierenrinden-Achse steht. Es ist bekannt, dass bei septischen Patienten die von den Nebennieren freigesetzten Glukokortikoide (Kortisol, Kortikosteron) eine wesentliche Rolle während der Unterdrückung einer exzessiven proinflammatorischen Reaktion spielen. Die Nebenniereninsuffizienz tritt in großer Anzahl bei Patienten im septischen Schock auf und ist verantwortlich für die erhöhte Sterblichkeit der an Sepsis Erkrankten. Im Rahmen des angeborenen Immunsystems spielen die sogenannten Toll-like Rezeptoren (TLRs) eine bedeutende Rolle bei der Erkennung von pathogen-assoziierten Molekülen. Interaktionen zwischen dem Immunsystem und dem endokrinen Stresssystem sind bekannt. Demzufolge ist eine gut aufeinander abgestimmte Antwort des adrenalen Systems und des Immunsystems für das Überleben während einer schweren Entzündungsreaktion von besonderer Bedeutung. Die vorliegende Arbeit befasst sich mit der Rolle von TLR-2, TLR-4 und TLR-9 während adrenalem Stress. Die Ergebnisse zeigen, dass das Fehlen von TLR-2 oder TLR-4, aber nicht TLR-9 zur Änderung der Morphologie der Nebennieren, bezüglich ihrer Größe und zellulären Struktur, bei den Mäusen führt. Dennoch scheint diese Änderung den Phänotyp der TLR knock-out Mäuse nicht zu beeinträchtigen. Mäuse mit fehlendem TLR-2, 4 oder 9 sind unfähig, sich adäquat auf einen inflammatorischen Stress, der durch die entsprechenden Liganden Lipopolysaccharid (LPS, TLR-4), Lipoteichonsäure (LTA, TLR-2) oder Cytidin-Phosphat-Guanosin-Oligodeoxynucleotid (CpG-ODN, TLR-9) hervorgerufen wird, zu antworten. Diese verminderte adrenale Stressantwort scheint mit der Abschwächung der systemischen und auch der intra-adrenalen Zytokin-Expressionen einherzugehen. Zusammenfassend deuten diese Ergebnisse darauf hin, dass TLR-2, 4 und 9 Schlüsselrezeptoren in der immun-adrenalen Antwort bei Entzündung und SIRS sind. Das enge funktionale Verhältnis zwischen den beiden Systemen sollte im Rahmen der Behandlung von entzündlichen Krankheiten, bei denen eine intakte adrenale Stressantwort erforderlich ist, berücksichtigt werden. Darüber hinaus könnten TLR Polymorphismen zu den zugrunde liegenden Mechanismen der beeinträchtigten adrenalen Stressantwort bei Patienten mit bakterieller Sepsis beigetragen haben

An approach for linguistic multi-attribute decision making based on linguistic many-valued logic

There are various types of multi-attribute decision-making (MADM) problems in our daily lives and decision-making problems under uncertain environments with vague and imprecise information involved. Therefore, linguistic multi-attribute decision-making problems are an important type studied extensively. Besides, it is easier for decision-makers to use linguistic terms to evaluate/choose among alternatives in real life. Based on the theoretical foundation of the Hedge algebra and linguistic many-valued logic, this study aims to address multi-attribute decision-making problems by linguistic valued qualitative aggregation and reasoning method. In this paper, we construct a finite monotonous Hedge algebra for modeling the linguistic information related to MADM problems and use linguistic many-valued logic for deducing the outcome of decision making. Our method computes directly on linguistic terms without numerical approximation. This method takes advantage of linguistic information processing and shows the benefit of Hedge algebra

STUDY ON ANTIOXIDANT ACTIVITIES OF THE AERIAL PARTS AND SOME COMPOUNDS ISOLATED FROM Archidendron clypearia ((Jack) I. Niels Part 2. ISOLATING, DETERMINING STRUCTURE AND ANTIOXIDANT CAPABILITY OF SOME COMPOUNDS FROM ETHYL ACETATE EXTRACT

The antioxidant activity in vitro of methanol extract of Archidendron clypearia was evaluated by in vitro tests on isolated liver cells of mouses with ED50 value ​​ of 2.18 μg/mL compared to that of curcumin of 1.87 µg/mL. Using combined chromatographic methods, four compounds were isolated from chloroform extract of the Archidendron clypearia. Their structures were elucidated to be daucosterol, 1-octacosanol, docosenoic acid, and methyl gallate by 1D- and 2D-NMR spectroscopic methods and in comparison with those reported in the literature. This is the first report of these compounds from the plant. All four compounds showed quite high antioxidant activity, for which methyl gallate was the highest one

CONCEPTS AND AWARENESS ABOUT SELF-HARM AND SUICIDAL THOUGHTS AMONG HIGH SCHOOL STUDENTS CURRENTLY

The article focuses on understanding concepts and awareness of suicidal thoughts and self – harm behaviors based on quantitative and qualitative data. The quantitative database will be taken from a survey of high school students living and studying in Ho Chi Minh City. The qualitative database is taken from in-depth interviews focusing on teachers, parents, and students. The article presents the main results of the research. First, focus on the research basis including subjects, objects, and research methodology. Second, include views on suicidal thoughts and self-harm from many different perspectives, manifestations and causes of these behaviors, the prevalence of self-harm/suicidal thoughts, and consequences. Third, conclude and propose some recommendations to minimize the problem

Pattern recognition receptors as key players in adrenal gland dysfunction during sepsis

Background: Undergoing systemic inflammation, the innate immune system releases excessive proinflammatory mediators, which finally can lead to organ failure. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), form the interface between bacterial and viral toxins and innate immunity. During sepsis, patients with diagnosed adrenal gland insufficiency are at high risk of developing a multiorgan dysfunction syndrome, which dramatically increases the risk of mortality. To date, little is known about the mechanisms leading to adrenal dysfunction under septic conditions. Here, we investigated the sepsis-related activation of the PRRs, cell inflammation, and apoptosis within adrenal glands. Methods: Two sepsis models were performed: the polymicrobial sepsis model (caecal ligation and puncture (CLP)) and the LTA-induced intoxication model. All experiments received institutional approval by the Regierungspräsidium Darmstadt. CLP was performed as previously described [1], wherein one-third of the caecum was ligated and punctured with a 20-gauge needle. For LTA-induced systemic inflammation, TLR2 knockout (TLR2-/-) and WT mice were injected intraperitoneally with pure LTA (pLTA; 1 mg/kg) or PBS for 2 hours. To detect potential direct adrenal dysfunction, mice were additionally injected with adrenocorticotropic hormone (ACTH; 100 μg/kg) 1 hour after pLTA or PBS. Adrenals and plasma samples were taken. Gene expressions in the adrenals (rt-PCR), cytokine release (multiplex assay), and the apoptosis rate (TUNEL assay) within the adrenals were determined. Results: In both models, adrenals showed increased mRNA expression of TLR2 and TLR4, various NLRs, cytokines as well as inflammasome components, NADPH oxidase subunits, and nitric oxide synthases (data not shown). In WT mice, ACTH alone had no effect on inflammation, while pLTA or pLTA/ACTH administration showed increased levels of the cytokines IL-1β, IL-6, and TNFα. TLR2-/- mice indicated no response as expected (Figure 1, left). Interestingly, surviving CLP mice showed no inflammatory adrenal response, whereas nonsurvivors had elevated cytokine levels (Figure 1, right). Additionally, we identified a marked increase in apoptosis of both chromaffin and steroid-producing cells in adrenal glands obtained from mice with sepsis as compared with their controls (Figure 2). ... Conclusion: Taken together, sepsis-induced activation of the PRRs may contribute to adrenal impairment by enhancing tissue inflammation, oxidative stress and culminate in cellular apoptosis, while mortality seems to be associated with adrenal inflammation

A Giant Frontal Meningioma with Psychiatric Symptoms in a Young Woman: A Case Report

Background:Frontal meningioma is often asymptomatic but patients might experience psychiatric symptoms. Since symptoms are atypical in giant meningioma, to the best of our knowledge, we present a rare clinical scenario. Case Presentation: A 24-year old female patient with no medical history presented with two months of depressive symptoms, personality changes such as easy irritability, and feelings of frustration and mental depression, as well as forgetfulness and blurred vision. Brain magnetic resonance imaging (MRI) revealed a well-defined markedly enhancing lesion in the left frontal region measuring 65 x 70 x 70 mm with mass effects to the adjacent brain tissue and associated surrounding edema which was pressed to the frontal horn of the lateral ventricle. The patient underwent frontal unilateral craniotomy and excision of the tumor. After surgery, the quality of life was improved. Conclusion: Meningioma with psychiatric symptoms is quite rare. This clinical case helps clinicians avoid missing symptoms and use appropriate management strategies for patients with giant meningiomas

Large displacements of FGSW beams in thermal environment using a finite element formulation

The large displacements of functionally graded sandwich (FGSW) beams in thermal environment  are studied using a finite element formulation. The beams are composed of three layers, a homogeneous core and two functionally graded face sheets with volume fraction of constituents following a power gradation law. The material properties of the beams are considered to be temperature-dependent.  Based on Antman beam model and the total Lagrange formulation, a two-node nonlinear beam element taking the effect of temperature rise into account  is formulated and employed in the study. The element with explicit expressions for the internal force vector and tangent stiffness matrix is derived using linear interpolations and reduced integration technique to avoid the shear locking. Newton-Raphson based iterative algorithm is employed in combination with the arc-length control method to compute the large displacement response of a cantilever FGSW beam subjected to end forces.  The accuracy of the formulated element is confirmed through a comparison study. The effects of the material inhomogeneity, temperature rise and layer thickness ratio on the large deflection response of the beam are examined and highlighted

ASSESSMENT OF THE POTENTIAL FOR DEVELOPMENT OF AGRITOURISM IN BINH DINH PROVINCE, VIETNAM

This study evaluates the potential for agritourism development in Binh Dinh Province, Central Vietnam. The analytical hierarchical process is used to determine the weights of four factors with 25 measurement criteria to assess agritourism potential. The research results show that Binh Dinh Province has great agritourism potential based on four evaluation factors, including (1) local agricultural tourism resources, (2) the trend for agritourism development and the agritourism market, (3) the local community’s willingness, and (4) the supporting activities of the local government. In particular, the local agricultural tourism resources factor received the highest score, followed by the local community’s willingness and the supporting activities of the local government. The trend for agritourism development and the agritourism market was rated the lowest. Therefore, Binh Dinh has viable opportunities to encourage the growth of agritourism to improve farmers’ livelihoodsDu lịch nông nghiệp đem lại nhiều cơ hội cho phát triển kinh tế cũng như đa dạng hóa các loại hình du lịch và cải thiện đời sống sinh kế của người dân. Nghiên cứu sử dụng phương pháp phân tích thứ bậc (AHP) để tính các trọng số của các tiêu chí đánh giá tiềm năng phát triển du lịch nông nghiệp tại các huyện, thị xã phía bắc tỉnh Bình Định. Tiếp theo, kết quả mô hình hóa sơ đồ mạng cho thấy cả 4 địa phương An Lão, Hoài Ân, Phù Mỹ, thị xã Hoài Nhơn đều được đánh giá ở mức điểm cao về tiềm năng phát triển du lịch nông nghiệp trên các khía cạnh tài nguyên du lịch, xu hướng phát triển du lịch, sự ủng hộ của người dân địa phương và sự quan tâm của chính quyền địa phương. Tuy nhiên, yếu tố xu hướng phát triển thị trường du lịch nông nghiệp được đánh giá ở mức điểm thấp hơn. Điều này cũng xuất phát từ việc phát triển du lịch nông nghiệp tại các huyện, thị xã phía Bắc tỉnh Bình Định cũng mới bắt đầu nhận được sự quan tâm trong vài năm gần đây, số lượt khách tham quan các huyện, thị xã phía Bắc tỉnh Bình Định còn ít so với tiềm năng du lịch của địa bàn

An Overview of Sustainable Ocean Resources for Socio-economic Development in Vietnam

Vietnam is one of the nation with long coastal with many valuable resources, which is the basis for the economy development from the ocean-based activities. This paper outlined the main maritime resources and their contribution to the socio-economic development in Vietnam. The raw data was collected from the readable sources such as General Statistics Office of Vietnam, Vietnam meteorological and meteorological data center…. as well as from the practical investigation. This raw data was processed and analyzed in order to have a general view on the majority marine resources in Vietnam. The results showed that there were 5 main resources (oil, fisheries, natural hydrate, green energy, and tourism) from the ocean, which significantly contribute to the economy development of Vietnam. The highest contribution of the oil value to the GDP was witnessed in 2011 with 26.6% of the GDP. While the value of the fisheries and tourism increased every year, the natural hydrate and energy from the ocean are still young areas, however, they come one step closer to the exploitation, which can greatly contribute to the Vietnam economy growth. With these valuable resources from the sea, Vietnam need to have reasonable policies and strategies for the management, exploitation, and export in order to able to effectively use of these resources for the sustainable economy development. Keywords: Ocean resources, sustainable development, fisheries, crude oil exploitation DOI: 10.7176/JRDM/69-05 Publication date:September 30th 202