La inflamación desde una perspectiva inmunológica: desafío a la Medicina en el siglo XXl / Inflammation from an immunologic perspective: a challenge to medicine in the 21st century

RESUMEN Introducción: La inflamación es una respuesta homeostática del organismo. Es uno de los principales motivos de consulta en Cuba y el mundo. Existe una percepción errónea de que es una entidad aislada y siempre patológica. Es un proceso dinámico, complejo, sistémico y multifactorial. Por eso constituye un reto el dilucidar los elementos, cambios tisulares que causa y cómo proceder en la clínica ante un cuadro inflamatorio. Objetivo: Describir la inflamación, su clasificación, elementos involucrados y cambios sistémicos desde una perspectiva inmunológica. Material y Métodos: Se realizó una revisión sobre el tema empleando la bibliografía actualizada y luego se consultaron artículos de libre acceso en las bases de datos Pubmed y Scielo en el período de enero de 2013 a diciembre de 2018. Desarrollo: La inflamación puede clasificarse según el daño, tiempo o los efectores involucrados. Las principales moléculas son las citocinas como TNF-α, IFN-γ, IL-1β, IL-10, IL-6, TGF-β. Participan células como los neutrófilos, mastocitos, macrófagos, linfocitos T y las del endotelio vascular. Durante el proceso inflamatorio se modifican las funciones de casi todos los sistemas de órganos. En ciertos tipos de inflamación, es la respuesta adaptativa quien origina y perpetúa el proceso inflamatorio. Conclusiones: En la actualidad se desconocen los acontecimientos que desencadenan inflamación crónica y cómo ocurre el daño tisular. El mayor desafío consiste en dilucidar las causas y mecanismos inmunológicos que conllevan a las manifestaciones inflamatorias sistémicas que se manifiestan como enfermedades neurológicas, cardiovasculares y autoinmunes, entre otras.

ABSTRACT Introduction: Inflammation is a homeostatic response of the body. It is one of the main reasons for consultation in Cuba and throughout world. There is a misperception that it is an isolated and always pathological entity. It is a dynamic, complex, systemic, and multifactorial process. Therefore, it is a challenge to elucidate the elements and the tissue changes that it causes to establish the best way to improve the clinical practice related to an inflammatory process. Objective: To describe inflammation, its classification, elements involved, and systemic changes from an immunological perspective. Material and Methods: A review of the topic was made using the updated bibliography. Free-access articles were consulted in Pubmed and Scielo databases in the period from January 2013 to December 2018. Development: Inflammation can be classified according to the damage, time or effectors involved. The main molecules are the cytokines like TNF-α, IFN-γ, IL-1β, IL-10, IL-6, TGF-β. Some cells participate such as neutrophils, mastocytes, macrophages, T-lymphocyes, and the vascular endothelium. During the inflammatory process, the functions of almost all organ systems are modified. It produces systemic changes that are observed in physiological processes such as pregnancy or aging. Sometimes inflammation triggers diseases such as cardiovascular and neurological ones, and cancer. The pathophysiological mechanisms have not been clarified. Conclusions: Currently, the events that trigger chronic inflammation and how tissue damage occurs are unknown. The biggest challenge is to elucidate the causes and immunological mechanisms that lead to inflammatory manifestations that are expressed as systemic neurological, cardiovascular and autoimmune diseases, among others.

Study on anti-inflammatory activities in vitro and in vivo and relation of fingerprint with pharmacodynamics of Notopterygii Rhizoma et Radix from three commercial specifications / 中草药

Objective: To explore the difference of anti-inflammatory effects in vitro and in vivo between Canqiang, Tiaoqiang and Datouqiang, and to obtain the anti-inflammatory active substances by relation of fingerprint with pharmacodynamics. Methods: Dimethylbenzene for the induction of a mouse ear edema in vivo and LPS-stimulated RAW 264.7 cells in vitro were used to investigate the anti-inflammatory activity, inflammatory factors such as nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by NO kit and ELISA kit, and the gray correlation analysis method was used to analyze the correlation between the peak area and the anti-inflammatory activity of the fingerprint features of each sample. Results: Different commercial specifications presented inhibition on acute inflammation of ear edema and inflammatory factors NO, TNF-α and IL-6, and anti-inflammatory effects were Canqiang > Datouqiang > Tiaoqiang. The chemical composition represented by 40 characteristic peaks was related to anti-inflammatory activity, and 17 characteristic peaks were highly correlated with this effect, among which three peaks were known components, namely chlorogenic acid, ferulic acid and isoimperatorin. Conclusion: The anti-inflammatory effect of Canqiang was the most significant, which was consistent with Canqiang being the most expensive and effective in the market, also with traditional grading standards. This study initially obtained anti-inflammatory active substances were chlorogenic acid, ferulic acid and isoimperatorin.

Esteatose hepática altera acúmulo celular em tilápias do Nilo durante aerocistite infecciosa / Hepatic steatosis alters cellular recruitment during induced aerocystitis in Nile tilapia

O presente estudo avaliou a hepatotoxicidade induzida pelo CCl4 durante o efeito glicocorticoide da dexametasona (DEX) na fisiopatologia da reação inflamatória aguda em tilápias do Nilo, Oreochromis niloticus, correlacionando a funcionalidade hepática à cinética de acúmulo celular em aerocistite infecciosa. Para tal, utilizou-se 84 tilápias do Nilo distribuídas em 4 tratamentos: controle, CCl4, DEX e CCl4+DEX. Sendo amostrados 7 animais por tratamento em três períodos, isto é: seis, 24 e 48h após indução de inflamação. Utilizou-se CCl4 em dose única de 0,5mL/kg, via intraperitoneal para causar o transtorno hepático. Para indução da aerocistite utilizou-se inóculo de Aeromonas hydrophila. A dexametasona foi administrada via intramuscular na dose de 2 mg/kg de peso vivo. Os resultados revelaram que quanto maior foi à atividade sérica de aspartato aminotransferase (AST) maior foi a alteração somática do fígado, sendo estes achados inversamente proporcionais ao acúmulo celular no foco inflamatório, demonstrando menor número de células inflamatórias nos animais acometidos com maior grau de distúrbios hepáticos induzidos pelo CCl4. O estudo histopatológico revelou alterações degenerativas transitórias na fase mais aguda, pois os fígados das tilápias revelaram o acúmulo lipídeos nos hepatócitos 6h após administração de CCl4, sendo esta degeneração gordurosa não mais observada nos tempos de 24 e 48h. Contudo, a administração de CCl4 em tilápias do Nilo resultou em degeneração hepática aguda e transitória, caracterizada pelo acúmulo de gordura nos hepatócitos, aumento de AST no sangue e hepatomegalia. Com a disfunção hepática houve comprometimento do recrutamento celular em aerocistite infecciosa, indicando que há participação do fígado na resposta imune inata em peixes.(AU)

The study evaluated the hepatotoxicity induced by CCl4 during the glucocorticoid effect of dexamethasone (DEX) on the pathophysiology of the acute inflammatory reaction in Nile tilapia, Oreochromis niloticus, correlating hepatic functionality with cellular accumulation kinetics in infectious aerocystitis. Eighty- four Nile tilapia were distributed into four treatments: control, CCl4, DEX and CCl4 + DEX. Seven tilapia were sampled per treatment in three periods: 6, 24 and 48h after induction of inflammation. CCl4 was used in a single dose of 0.5mL/kg intraperitoneally to cause hepatic disorder. Aeromonas hydrophila inoculum was used to induce aerocystitis. Dexamethasone was administered intramuscularly at the dose of 2mg/kg b. w. The results revealed a higher serum aspartate transaminase (AST) activity associated with greater somatic liver alteration, being these findings inversely proportional to the cellular accumulation in the inflammatory focus, demonstrating a lower number of inflammatory cells in the animals affected with a higher degree of hepatic disorders induced by CCl4. The histopathological study revealed transient degenerative changes in the most acute phase, as livers of tilapia showed accumulation of lipids in hepatocytes 6 hours after administration of CCl4, and this fatty degeneration was no longer observed in 24 and 48h. However, administration of CCl4 in Nile tilapia resulted in acute and transient liver degeneration, characterized by accumulation of fat in hepatocytes, increased AST in the blood and hepatomegaly. With liver dysfunction there was compromise of cellular recruitment in infectious aerocystitis, indicating that there is liver involvement in the innate immune response in tilapia.(AU)

Phytochemical analysis of Juglans regia oil and kernel exploring their antinociceptive and anti-inflammatory potentials utilizing combined bio-guided GC-FID, GC-MS and HPLC analyses

ABSTRACT Juglans regia L., Juglandaceae, is broadly used due to its immunomodulatory effects, potentials in protecting against many sever-disorders, and high safety-profile. The aim of this work is to make a phytochemical analysis of J. regia oil and kernel exploring their antinociceptive and anti-inflammatory potentials utilizing combined bio-guided gas chromatography with mass spectrometer (GC-MS), gas chromatography with flame ionization detection (GC-FID) and reversed-phase high-performance liquid chromatography (RP-HPLC) analyses. Combined bio-guided GC-MS, GC-FID and RP-HPLC analyses is an innovative-combined-technique aiming at efficiently analyzing various-extracts phytochemical and biological characters. The J. regia oil and kernel ethyl-acetate extract were monitored during exploring their possible acute-antinflammatory, antidiabetic and antidiabetic-neuropathy. Glycated-hemoglobin, serum-insulin, serum-catalase and lipid-peroxidation levels have been also monitored. Combined bio-guided GC-FID, GC-MS and HPLC analyses have shown to be an efficient analyzing-method through identifying the most active compound, linoleic acid. Linoleic acid has shown the highest improvement of the acute inflammatory-pain, chronic blood-glucose level reduction, serum-insulin elevation, and normalization of glycated-hemoglobin levels. J. regia oil has shown more lipid-peroxidation reduction, while kernel ethyl-acetate extract has shown more acute-blood-glucose level reduction and serum-catalase levels elevation. Compared to tramadol, the highest-doses of J. regia oil, kernel ethyl-acetate extract, and linoleic acid have shown higher antinociceptive-potentials in amelioration of thermal-hyperalgesic and anti-allodynic neuropathic-pain. Thus, the antinflammatory, the reduction of oxidative-stress, and the insulin-secretagogue potentials might be among the possible mechanisms of improvement of neuropathic-pain. In correlation to conventional-techniques, the combined bio-guided analyses have shown to be an efficient innovative-combined technique. After further clinical studies, J. regia might be utilized as a possible-remedy for various painful-syndromes.

Induced aerocystitis and hemato-immunological parameters in Nile tilapia fed supplemented diet with essential oil of Lippia alba / Aerocistite induzida e parâmetros hemato-imunológicos em tilápia do Nilo suplementada com óleo essencial de Lippia alba

The present study evaluated the dietary supplementation with essential oil of Lippia alba on the hemato-immunological parameters of Nile tilapia (Oreochromis niloticus) submitted to acute inflammation induced by carrageenin injection in the swim bladder. For a period of 45 days, 96 fish were divided in four treatments in triplicate, as follows: fish fed supplemented diet with essential oil of L. alba (4 mL kg-1 dry ration) injected with carrageenin; fish fed supplemented diet with cereal alcohol injected with carrageenin; fish fed unsupplemented diet with essential oil injected with carrageenin; fish fed unsupplemented diet and noninjected. Cortisol levels, erythrogram, leukogram and the inflammatory infiltrate were analyzed 6 h after inflammatory stimulus. Carrageenin-injected fish showed acute inflammatory reaction in the swim bladder characterized by higher infiltrate of neutrophils and monocytes. The circulating neutrophils number was significantly higher in fish fed L. alba when compared to other treatments. No difference in cortisol levels was found. For dose, time and administration form tested, supplementation with essential oil of L. alba did not present anti-inflammatory activity. On the other hand, influence of dietary supplementation was observed on the neutrophils number after induced aerocystitis highlighting its immunomodulatory characteristic.(AU)

O presente estudo avaliou a suplementação dietária com óleo essencial de Lippia alba sobre os parâmetros hemato-imunológicos em tilápias do Nilo (Oreochromis niloticus) submetidas à inflamação aguda induzida por carragenina na bexiga natatória. Pelo período de 45 dias, 96 peixes foram divididos em quarto tratamentos em triplicata: a) peixes suplementados com óleo esencial de L. alba (4 mL kg-1 de ração) injetados com carragenina; b) peixes suplementados com álcool de cereais injetados com carragenina; peixes não suplementados com óleo essencial injetados com carragenina; c) peixes não suplementados não injetados. Os níveis de cortisol, eritrograma, leucograma e o infiltrado inflamatório foram analisados seis horas após o estímulo inflamatório. Peixes injetados com carragenina apresentaram reação inflamatória aguda na bexiga natatória caracterizada por maior infiltrado de neutrófilos e monócitos. O número de neutrófilos circulantes foi significativamente maior nos peixes suplementados com L. alba quando comparado aos outros tratamentos. Não houve diferença nos níveis de cortisol. Para a dose, o tempo e a forma de administração testada, a suplementação com óleo essencil de L. alba não apresentou atividade anti-inflamatória. Por outro lado, foi constatada influência da suplementação dietária no número de neutrófilos após a aerocistite enfatizando a sua característica imunomoduladora.(AU)

Studies on Anti-inflammatory Effects of Gutong Plasters on Acute Inflammation in Rats / 中国药师

Objective: To study the anti-inflammatory effect and mechanism of Gutong plasters in acute inflammatory model of rats. Methods:Totally 60 SD rats were randomly divided into the blank group,the model group,Gutong plasters at low,medium and high dose groups(0.594,1.188 and 2.376 g/patch containing crude drug 0.48,0.96 and 1.92 g,respectively) and prednisone ace-tate group(0.005 4 g·kg-1). The acute inflammation model was prepared by injecting 5% formaldehyde into right side of foot plan-tar. And then,the anti-inflammatory effect was evaluated by measuring the foot plantar volume. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of nitric oxide(NO),histamine(HIS) and 5-hydroxytryptamine(5-HT) in serum and inflam-matory tissue,the levels of prostaglandin E2(PGE2),tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β) and interleu-kin 6 (IL-6) in inflammatory tissue were also determined. Pathological changes were observed through the pathological sections pre-pared by HE staining. Results:When compared with the model group,Gutong plasters could significantly inhibit the swelling of foot plantar in inflammatory rats(P<0.01). At the same time,Gutong plasters could significantly reduce the levels of NO,5-HT and HIS in serum and inflammatory tissue in different degrees(P<0.05 or P<0.01),significantly reduce the content of PGE2in inflammatory tissue (P<0.05 or P<0.01),increase the content of IL-6 in inflammatory tissue and improve the pathological changes of inflammato-ry tissues (the pathological score was significantly reduced). In partical indictor changes,Gutong plasters and prednisone acetate showed an equal effect.In addition,Gutong plasters didn't show significant dose-dependent manner in inhibiting foot swelling,affect-ing inflammatory mediators and improving pathological changes(P>0.05). Conclusion:Gutong plasters have better anti-inflammato-ry effect in the acute inflammation model induced by formaldehyde in rats. The anti-inflammatory effect may be associated with the de-crease of the levels of NO,5-HT and HIS in serum and inflammatory tissue,the decrease of the content of PGE2and the increase of the content of IL-6 in inflammatory tissue. In addition,the anti-inflammatory effect may be relevant to improving the local inflammatory tis-sue subcutaneous edema and inflammatory cell infiltration.

Anti-inflammatory evaluation and acute toxicity of three food supplements that contain Moussonia deppeana

Objective To identify the anti-inflammatory activity through two murine models and in the median Lethal Dose (LD

Anti-inflammatory evaluation and acute toxicity of three food supplements that contain Moussonia deppeana

OBJECTIVE@#To identify the anti-inflammatory activity through two murine models and in the median Lethal Dose (LD) of three dietary supplements that contain Moussonia deppeana.@*METHODS@#The anti-inflammatory activity of three dietary supplements (Cicatrisan/Gastricus, Gastinol, and Gastrovita) EtOH extracts was evaluated by TPA and by carrageenan murine models; also, median Lethal Dose (LD) was determined. Verbascoside was quantified by High-Performance Liquid Chromatography. β-sitosterol, stigmasterol and the mixture of ursolic and oleanolic acids were identified in all supplements by TLC; however, none of these dietary supplements contain verbascoside.@*RESULTS@#For the TPA model, Cicatrisan/Gastricus generated a notable effect with 38.24% inhibition. While in the carrageenan model, it also exhibited noteworthy anti-inflammatory activity of ear edema with 66.39% of paw edema inhibition at 150 mg/kg, followed by Gastinol and Gastrovita with ≈50% at 300 mg/kg. Finally, LD was >2 g/kg for all supplements, when was administered intragastrically and Body Weight (BW) gain in mice was not altered after 14 days.@*CONCLUSIONS@#Of the three food supplements containing M. deppeana, only the EtOH extract from Cicatrisan/Gastricus formulation (tablets) showed significant anti-inflammatory activity in both experimental models and the LD was >2 g/kg.

Anti-inflammatory activity and acute toxicity studies of hydroalcoholic extract of Herissantia tiubae

ABSTRACT Hydroalcoholic extract of aerial parts of Herissantia tiubae (K. Schum.) Brizicky, Malvaceae, was evaluated in experimental models of inflammation and toxicity. For toxicity assays, male and female Swiss mice were orally treated with hydroalcoholic extract of H. tiubae (2000 mg/kg) and analyzed by consumption of water and food, body weight, mortality and rates of major organ weights, as well as biochemical and hematological indexes. For anti-inflammatory effect, phlogistic agents such as carrageenan or acetic acid were used to evaluate paw edema, cell migration and cytokine production. It was also investigated the hydroalcoholic extract of H. tiubae in RAW 264.7 macrophage lineage by nitric oxide and cytokine productions. Swiss mice treated with hydroalcoholic extract of H. tiubae showed low toxicity and (50 or 100 mg/kg) was able to reduce significantly (p < 0.01, p < 0.001) polymorphonuclear cell migration, TNF-α and IL-1β production in the carrageenan-induced peritonitis. However the hydroalcoholic extract of H. tiubae (50, 100 or 200 mg/kg) did not reduce carrageenan-induced paw edema. Additionally, hydroalcoholic extract of H. tiubae did not present cytotoxicity at concentrations of 6.25, 12.5, 25 or 50 µg/ml but induced significantly decrease of NO, TNF-α and IL-6 production in macrophage lineage. This study suggests that hydroalcoholic extract of H. tiubae has anti-inflammatory activity by inhibiting cell migration mainly by decreasing the inflammatory cytokine levels at the inflamed site independently of the anti-edematogenic effect.

Effect of Acute Placenta Inflammatory Changes on Fetal Outcome among Paturients in Nigeria.

Introduction: The placenta unit is significant for the survival of the fetus. Infections from the mother can cause histologically identifiable inflammatory changes in the placenta, which may adversely affect the fetus. Aim: To identify the inflammatory changes in the placenta and its effect on fetal outcome. Study Design: Cross sectional study. Place and Duration of Study: Department of Obstetrics and Gynaecology and Department of Anatomical pathology of the University of Port Harcourt Teaching hospital, between 1st September – 31st of December, 2015. Methods: Histological analysis of 189 placenta tissues of singleton birth paturients was carried out. The sociodemographic characteristics of patients and the fetal outcome was collated and analyzed. The information obtained was processed using the SPSS version 20 software and Epi info software version 7. Results were presented in tables; test of association was done using student’s t-test with P value < 0.05 set as significant. Results: The mean age of patients was 30.9±4.6 years with age range of 19-48years. Acute placental inflammatory changes of varying grades were noted in 64.6%(122) of placenta with severe inflammatory changes constituting 8.5%(16) of all examined placentae. Severely inflamed placenta was associated with birth asphyxia (P=0.0000033) and fetal demise (P=0.0352). Conclusion: Acute inflammatory changes are common among paturients in Port Harcourt Nigeria. These changes in placenta are associated with birth asphyxia and fetal demise especially when they are severe.

FGF-21 inhibits lipopolysaccharide induced acute inflammation and its molecular mechanism / 中国药学杂志

OBJECTIVE: To study the effects of fibroblast growth factor-21 (FGF-21) on acute inflammation induced by lipopolysaccharide (LPS) and its mechanism. METHODS: Mouse model of acute inflammation was established by injection of LPS and treated with FGF-21 at high, medium and low doses, the pathological changes were detected with HE staining, the expression level of TNF-α, IL-1β, IL-6 and IL-17 in serum and peritoneal macrophage were determined by ELISA and Real-time PCR. NF-κB p65 in macrophage cells was analyzed by confocal laser scanning microscope and Western-blotting. RESULTS: FGF-21 treatment reduced lung damage and inflammatory cell infiltration and decreased the expression level of TNF-α, IL-1β, IL-6 and IL-17 in both serum and peritoneal macrophage. The results of confocal laser scanning microscope and Western-blotting both showed that FGF-21 could inhibit NF-κB transferring to the nucleus. CONCLUSION: FGF-21 could regulate the immune system by acting on macrophage. Relieving the inflammatory response in mice through NF-κB signal pathway may be one of the mechanisms FGF-21 regulating immune system.

Multi-center clinical trial of Xiao'er Feire Kechuan Granule on acute inflammation of pharynx and trachea with syndrome of pedo-anemopyretic cold with phlegm / 中草药

Objective: To evaluate the efficacy and safety of Xiao'er Feire Kechuan Granule in treating on acute inflammation of the pharynx and the trachea with syndrome of pedo-anemopyretic cold with phlegm. Methods: The stratified blocked randomization, positive drug (Jizhi Syrup) parallel contrast, double blind, double dummy, non-inferiority test, and multi-center research were applied to this study. Results: A total of 210 cases were collected, and each group with 105 cases. The total effective rates of disease in the treatment and control groups were 96.04% and 96.08%, respectively (per protocol analysis, PPS), and the total effective rates of syndrome in the treatment and control groups were 97.03% and 98.04% (PPS), respectively. The results of non-inferiority test indicated that the efficiency to the patients in the treatment group was no worse than that in the control group. The disappearance rate of sore red swollen throat in the two groups, respectively was 57.43% and 43.14% (PPS); The treatment group was superior to the control group, the difference between the two groups was significant (P<0.05). Compared with the disappearance rate of other single syndromes and the incidence of complications, the difference between the two groups was not significant. There was no clinical adverse reaction in both groups. Conclusion: The curative effect of Xiao'er Feire Kechuan Granule is not inferior to Jizhi Syrup, and compared with the disappearance rate of sore red swollen throat, it is superior to Jizhi Syrup. In addition to, Xiao'er Feire Kechuan Granule has high safety.

Proteínas de fase aguda em cães e gatos / Acute-phase proteins in dogs and cats / Proteínas de fase aguda en perros y gatos

As proteínas de fase aguda (PFA) são um grupo de proteínas sanguíneas que apresentam alterações nas suas concentrações em animais acometidos por infecções, inflamações, trauma cirúrgico ou mesmo submetido ao estresse. São proteínas que alteram as suas concentrações em pelo menos 25% durante a inflamação. As PFA consistem em proteínas de fase aguda negativa e/ou positiva, diminuindo ou aumentando a sua concentração, respectivamente, em resposta a um estímulo inflamatório. Dentre as PFA negativas mais importantes estão a albumina e a transferina. As PFA positivas são a haptoglobina (Hp), proteína C-reativa (CRP), amiloide A-sérico (SAA), ceruloplasmina (Cp), fibrinogênio e a alfa 1 glicoproteina ácida(APG). As avaliações da concentração das PFA e proteínas totais propiciam subsídios para adequada interpretação do estado de hidratação, bem como de inflamação, infecção, doença imunomediada e alteração da síntese proteica. Sendo as PFA mediadores inflamatórios das respostas imunes agudas, e consideradas marcadoras das lesões teciduais na sua fase aguda nos animais, é importante realizar uma revisão sobre as PFA mais importantes e suas funções nos cães e gatos.

Acute-phase proteins (APP) are a group of blood proteins exhibiting changes in their concentrations in animals suffering from infections, inflammation, surgical trauma or even which have been subjected to stress. These proteins present at least 25% changes in their concentrations during inflammation. APPs consist of negative- and positive-phase proteins that can decrease or increase their concentration in response to an inflammatory stimulus. The most important negative APP are albumin and transferrin; and the most important positive APP are haptoglobin (Hp) , C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin (Cp), fibrinogen and alpha 1 glycoprotein acid (AGP). APP concentration and total protein reviews provide information for proper interpretation of hydration status, as well as inflammation, infection, immune-mediated diseases and impaired protein synthesis. APPs are inflammatory mediators of acute immune responses and are considered markers for tissue damages in the acute phase in animals. Therefore, it is important to further review the most important APPs and their functions in dogs and cats.

Las proteínas de fase aguda (PFA) son un grupo de proteínas sanguíneas que presentan cambios en sus concentraciones en animales acometidos por infecciones, inflamaciones, trauma quirúrgico o mismo sometido a estrés. Son proteínas que alteran sus concentraciones de al menos 25 % durante la inflamación. Las PFA consisten en proteínas de fase aguda negativa y/o positiva, disminuyendo o aumentando su concentración, respectivamente, en respuesta a un estímulo inflamatorio. Entre las PFA negativas más importantes están la albúmina y la transferrina. Las PFA positivas son la haptoglobina (Hp), proteína C - reactiva (CRP), amiloideo A-sérico (SAA), ceruloplasmina (Cp), fibrinógeno y la alfa 1-glicoproteína ácida (APG). Las evaluaciones de la concentración de las PFA y proteínas totales proporcionan informaciones para la interpretación apropiada del estado de hidratación, así como de la inflamación, infección, enfermedad inmune-mediada y alteración de síntesis proteica. Siendo las PFA mediadores de respuestas inmunes inflamatorias agudas y consideradas marcadoras de lesiones tisulares en su fase aguda en los animales, es importante llevar a cabo una revisión sobre las PFA más importantes y sus funciones en los perros y gatos.

Novas perspectivas para o papel de amilóide sérica A (SAA) na obesidade e resistência à insulina / New insights into the role of serum amyloid A (SAA) on obesity and insulin resistance

Chronic low-grade endotoxemia is an important player in obesity and insulin resistance associated to a high-fat diet (HFD). On the other hand, although it is known that intense endotoxemia and infection reduce appetite and induce intense catabolism, leading to weight loss during the acute inflammatory phase, the late effects of an intense endotoxemia were previously unexplored. Here we report that, besides the concurrent effects, multiple and intense endotoxemia causes long lasting biochemical alterations in the adipose tissue that intensify the harmful effects of a HFD. Mice submitted to multiple and severe endotoxemia had increased the adipose tissue expression of TLR-4, CD14 and SAA3, remaining altered after one week in recovery. When associated to a HFD, mice previously submitted to acute endotoxemia showed a more severe weight gain and impaired insulin sensitivity. Adopting the HFD as an obesogenic stimulus, we evaluated the participation of the protein serum amyloid A (SAA) in obesity development. Using a SAA-targeted antisense oligonucleotide, we observed that the depletion of SAA prevented metabolic alterations, endotoxin elevation, weight gain and insulin resistance in a diet-induced obesity protocol. Inadequate sleep is another important factor to be considered in the obesity epidemic. We found that sleep restriction (SR) causes biochemical and morphological alterations in mice adipose tissue. The levels of serum resistin and the adipose tissue mRNA expression of resistin, TNF-α and IL-6 were increased after SR. When associated to a HFD, mice previously submitted to SR gained more weight with increased macrophage infiltration in the epididymal adipose tissue, and insulin resistance. SAA is also part of the initial biochemical alterations caused by SR. It was observed that the expression of SAA in liver and adipose tissue is upregulated, with return to baseline when sleep is restored. Furthermore, 48 hours of total sleep restriction in healthy human volunteers also caused a serum elevation in SAA concentrations. Considering that SAA induces cell proliferation, we suggest that situations with an increase in SAA production and the consecutive preadipocyte proliferation would prime the adipose tissue to further adipocyte differentiation and hypertrophy. Furthermore, we suggest that SAA alter LPS signaling, possibly inhibiting its clearance. The mechanism associating inflammation and obesity is complex and encompass a diversity of factors; the inflammatory protein SAA may be one of them. In conclusion, our data describes the relationship between SAA, acute inflammation, sleep restriction and obesity

Endotoxemia crônica de baixo grau tem um importante papel na obesidade e resistência à insulina associada a uma ração hiperlipídica. Por outro lado, embora se saiba que a endotoxemia intensa e infecção reduzam o apetite e induzam a um intenso catabolismo, conduzindo a perda de peso durante a fase aguda da inflamação, os efeitos tardios da endotoxemia intensa nunca foram explorados. Aqui mostramos que, além dos efeitos correntes, a endotoxemia aguda provoca alterações bioquímicas prolongadas no tecido adiposo que intensificam os efeitos deletérios de uma ração hiperlipídica. Camundongos submetidos à endotoxemia aguda apresentaram aumento na expressão de TLR-4, CD14 e SAA3 no tecido adiposo, permanecendo alteradas após uma semana em recuperação. Quando associado a uma ração hiperlipídica, os camundongos previamente submetidos à endotoxemia aguda mostraram um ganho de peso mais pronunciado e uma maior resistência à insulina. Adotando a ração hiperlipídica como um estímulo obesogênico, foi avaliada a participação da proteína amilóide sérica A (SAA) no desenvolvimento da obesidade. Usando um oligonucleotídeo antisense anti-SAA, observamos que a depleção da SAA previne as alterações metabólicas, elevação de endotoxina, ganho de peso e resistência à insulina associadas a ração rica em gordura. O sono inadequado é outro fator importante a ser considerado na epidemia de obesidade. Descobrimos que a restrição do sono (SR) provoca alterações bioquímicas e morfológicas no tecido adiposo de camundongos. A concentração de resistina no soro e a expressão de mRNA no tecido adiposo de resistina, TNF-α e IL- 6 foram aumentadas após SR. Quando associado a uma ração hiperlipídica, os camundongos submetidos previamente à SR ganharam mais massa com aumento da infiltração de macrófagos no tecido adiposo epididimal, e resistência à insulina. SAA também faz parte das alterações bioquímicas iniciais provocadas pelo SR. Observou-se que a expressão de SAA no fígado e tecido adiposo é regulada positivamente, com retorno ao basal quando o sono é restaurado. Além disso, 48 horas de restrição de sono total em voluntários humanos saudáveis também causou uma elevação nas concentrações séricas de SAA. Considerando que SAA induz proliferação, sugerimos que situações onde ocorra aumento na produção de SAA e a consecutiva proliferação celular, o tecido adiposo se tornaria predisposto a futura diferenciação e hipertrofia. Além disso, sugerimos que SAA altera a sinalização de LPS, possivelmente inibindo sua depuração. O mecanismo de associação entre a inflamação e a obesidade é complexo e inclui uma diversidade de fatores; a proteína inflamatória SAA pode ser um deles. Em conclusão, nossos dados descrevem a relação entre SAA, inflamação aguda, restrição do sono e obesidade

Anti-inflammation Effects of Cacumen Biotae Water Decoction on Mice with Auricle and Abdominal In-flammation / 中国药房

OBJECTIVE:To study the anti-inflammation effects of cacumen biotae water decoction on mice with auricle and ab-dominal inflammation. METHODS:Mice were randomized into a normal control group,a model group,a positive control group (0.25 g/L aspirin)and cacumen biotae high-dose,medium-dose and low-dose [1,0.5 and 0.25 g(medicinal materials)/L] groups, respectively marked as groups A,B,C,D,E and F,with 10 mice in each group. The mice were given drugs ig for 5 consecutive days. The models of auricle and abdominal inflammation were established for all groups except the normal control group. The con-tents of tumor necrosis factor α(TNF-α)and interleukin 1(IL-1)in the serum of mice with auricle inflammation were determined, and the swelling degree and swelling rate were calculated. The contents of TNF-α,IL-1 and acid-sensing ion channels 1a(ASIC1a) in the liver tissues of mice with abdominal inflammation and the concentration of proteins in the peritoneal lavage fluid(ΔA)there-of were detected. RESULTS:For mouse models of auricle inflammation,the contents of TNF-α and IL-1 in serum in group B were higher than in group A;the swelling degree and swelling rate and the contents of TNF-α and IL-1 in groups C,D,E and F were lower than in group B,and those of group E and F were higher than in group C. There were statistical differences(P<0.05). For mouse models of abdominal inflammation,the contents of TNF-α,IL-1 and ASIC1a in liver tissues and ΔA in group B were higher than in group A;the contents of TNF-α,IL-1 and ASIC1a as well as ΔA in groups C,D,E and F were lower than in group B. There were statistical differences(P<0.05). CONCLUSIONS:Cacumen biotae water decoction has anti-effect on acute auricle and abdominal inflammation by a mechanism which may be related to decreasing TNF-α,IL-1 and ASIC1a.

Proteínas de fase aguda em cães e gatos / Acute-phase proteins in dogs and cats / Proteínas de fase aguda en perros y gatos

As proteínas de fase aguda (PFA) são um grupo de proteínas sanguíneas que apresentam alterações nas suas concentrações em animais acometidos por infecções, inflamações, trauma cirúrgico ou mesmo submetido ao estresse. São proteínas que alteram as suas concentrações em pelo menos 25% durante a inflamação. As PFA consistem em proteínas de fase aguda negativa e/ou positiva, diminuindo ou aumentando a sua concentração, respectivamente, em resposta a um estímulo inflamatório. Dentre as PFA negativas mais importantes estão a albumina e a transferina. As PFA positivas são a haptoglobina (Hp), proteína C-reativa (CRP), amiloide A-sérico (SAA), ceruloplasmina (Cp), fibrinogênio e a alfa 1 glicoproteina ácida (APG). As avaliações da concentração das PFA e proteínas totais propiciam subsídios para adequada interpretação do estado de hidratação, bem como de inflamação, infecção, doença imunomediada e alteração da síntese proteica. Sendo as PFA mediadores inflamatórios das respostas imunes agudas, e consideradas marcadoras das lesões teciduais na sua fase aguda nos animais, é importante realizar uma revisão sobre as PFA mais importantes e suas funções nos cães e gatos.

Acute-phase proteins (APP) are a group of blood proteins exhibiting changes in their concentrations in animals suffering from infections, inflammation, surgical trauma or even which have been subjected to stress. These proteins present at least 25% changes in their concentrations during inflammation. APPs consist of negative- and positive-phase proteins that can decrease or increase their concentration in response to an inflammatory stimulus. The most important negative APP are albumin and transferrin; and the most important positive APP are haptoglobin (Hp) , C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin (Cp), fibrinogen and alpha 1 glycoprotein acid (AGP). APP concentration and total protein reviews provide information for proper interpretation of hydration status, as well as inflammation, infection, immune-mediated diseases and impaired protein synthesis. APPs are inflammatory mediators of acute immune responses and are considered markers for tissue damages in the acute phase in animals. Therefore, it is important to further review the most important APPs and their functions in dogs and cats.

Las proteínas de fase aguda (PFA) son un grupo de proteínas sanguíneas que presentan cambios en sus concentraciones en animales acometidos por infecciones, inflamaciones, trauma quirúrgico o mismo sometido a estrés. Son proteínas que alteran sus concentraciones de al menos 25 % durante la inflamación. Las PFA consisten en proteínas de fase aguda negativa y/o positiva, disminuyendo o aumentando su concentración, respectivamente, en respuesta a un estímulo inflamatorio. Entre las PFA negativas más importantes están la albúmina y la transferrina. Las PFA positivas son la haptoglobina (Hp), proteína C - reactiva (CRP), amiloideo A-sérico (SAA), ceruloplasmina (Cp), fibrinógeno y la alfa 1-glicoproteína ácida (APG). Las evaluaciones de la concentración de las PFA y proteínas totales proporcionan informaciones para la interpretación apropiada del estado de hidratación, así como de la inflamación, infección, enfermedad inmune-mediada y alteración de síntesis proteica. Siendo las PFA mediadores de respuestas inmunes inflamatorias agudas y consideradas marcadoras de lesiones tisulares en su fase aguda en los animales, es importante llevar a cabo una revisión sobre las PFA más importantes y sus funciones en los perros y gatos.

Efficacy evaluation of budesonide spray atomization inhalation on ear-nose-pharyngeal-throat acute inflammation / 中国生化药物杂志

Objective To investigate the clinical efficacy of Budesonide spray atomization inhalation on ear-nose-pharyngeal-throat acute inflammation.Methods 120 patients with ear-nose-pharyngeal-throat acute inflammation were slected from April 2010 to April 2013 in Liuzhou People’s Hospital.They were randomly divided into control group(n=60 )and observation group (n=60 ).The patients in observation group were treated with budesonide spray atomization inhalation,while the patients in control group were treated with conventional ultrasonic aerosol inhalation,continous use for 5 days.Compare the improvement of throat pain,pharyngeal foreign body sensation,dyspnea,hoarseness and the average improving time after treatment in two groups. Results The total effective rate of throat pain,pharyngeal foreign body sensation,dyspnea,hoarseness and the average improving time in observation group was significantly better than that in control group,the difference was statistically significant(P<0.05 ).Conclusion Compared with conventional ultrasonic atomization inhalation,the efficacy of budesonide spray atomization inhalation on ear-nose-pharyngeal-throat acute inflammation is better.

Estudio preclínico del efecto de las esencias florales de Bach en la inflamación aguda / Preclinical effect of the Bach flower essence in acute inflammation

Introducción: los estudios preclínicos que de forma habitual preceden al uso de un medicamento convencional pudieran convertirse en la solución a la comprobación de las acciones terapéuticas de medicinas naturales como las flores de Bach. La inflamación aguda y los modelos experimentales que la simulan son herramientas útiles en este camino. Objetivo: evaluar la actividad antiinflamatoria de las esencias florales de Bach en un modelo de inflamación aguda en ratas. Métodos: se realizó un estudio preclínico experimental piloto controlado y aleatorizado a ciegas en la UTEX de la Universidad de Ciencias Médicas de Villa Clara en el mes de Diciembre del 2010. El modelo experimental consistió en la inducción de edema plantar con dextrán. Se conformaron en 5 grupos de 6 animales (en total 30 ratas). Se trataron con las esencias Beech, Vervain y Rescue Remedy, respectivamente; mientras que los 2 restantes fueron control (negativo con placebo y positivo con Difenhidramina). Resultados: se observaron diferentes efectos en los tratamientos utilizados. Beech y Vervain mostraron propiedades antiinflamatorias con diferencias significativas al placebo, cuestión que avala su utilización en el tratamiento de patologías donde la inflamación es un denominador común. Estas acciones fueron selectivas ya que Beech tuvo efecto inmediato y Vervain mostró actividad sobre la inflamación en tercera hora. Otro preparado, el Rescue Remedy, no mostró esta actividad diferente al placebo

Background: the preclinical studies that in their habitual form precede the use of a conventional drug, could become a solution to testing therapeutic actions of natural medications such as the Bach flowers. The acute inflammation and the experimental models that simulate it are very useful tools in this direction. Objective: to evaluate the antinflammatory activity of the Bach flower essence in an acute inflammation model in rats. Methods: a pilot experimental preclinical study, controlled and blindly randomized, was carried out at the UTEX of the Medical Sciences University of Villa Clara on December 2010. The experimental model consisted on the induction of plantar oedema with Dextran. 5 groups of 6 animals were formed (30 rats in total). They were treated with Beech and Vervain essences and Rescue Remedy respectively; while the remaining 2 formed the control group (negative with placebo and positive with Diphenhydramine). Results: different effects in the treatments were observed. Beech and Vervain showed antinflammatory properties with significant differences form placebo, condition that endorse their use in the treatment of pathologies where inflammation is a common factor. These actions were selective because Beech had an immediate effect and Vervain showed its activity on the inflammation in the third hour. Other preparation, the Rescue Remedy, showed that its activity was not different from placebo

Effects of Methanol Extract of Piper chaba Stem Bark on Acute Inflammation in Rats.

The plant Piper chaba Hunter (Piperaceae), a climbing glabrous shrub grows in plenty in southern Bangladesh. Popularly known as 'Choi' it is used as spices and believed to have medicinal value in a wide variety of disease conditions including arthritis, asthma, bronchitis and piles. In the present study, effect of methanol extract of Piper chaba stem bark on acute inflammation has been reported. The anti-inflammatory effect was studied in rats by injecting 0.1ml of 1% carrageenan suspension into the planter surface, where oedema of the rat's hind paw was used as an index of acute inflammation. Methanol extract of Piper chaba stem bark given orally 1 hour before injection at doses of 125 and 250 mg/kg body weight, produced significant (p< 0.05) anti inflammatory effect compared to control and the percentage of inhibition of oedema formation was 33% and 35% respectively, which however was less compared to aspirin (46%) and hydrocortisone (56%). The result suggest that in case of acute inflammation, Piper chaba stem bark possess mild to moderate anti inflammatory effect compared to that of aspirin and hydrocortisone.

Inflammatory and Tumor Stimulating Responses after Laparoscopic Sigmoidectomy

PURPOSE: Laparoscopic colectomy has clinical benefits such as short hospital stay, less postoperative pain, and early return of bowel function. However, objective evidence of its immunologic and oncologic benefits is scarce. We compared functional recovery after open versus laparoscopic sigmoidectomy and investigated the effect of open versus laparoscopic surgery on acute inflammation as well as tumor stimulation. MATERIALS AND METHODS: A total of 57 patients who were diagnosed with sigmoid colon cancer were randomized for elective conventional or laparoscopically assisted sigmoidectomy. Serum samples were obtained preoperatively and on postoperative day 1. C-reactive protein (CRP) and interleukin-6 (IL-6) were measured as inflammation markers, and vascular endothelial growth factor (VEGF) and insulin-like growth factor binding protein-3 (IGFBP-3) were used as tumor stimulation factors. Clinical parameters and serum markers were compared. RESULTS: Postoperative hospital stay (p=0.031), the first day of gas out (p=0.016), and the first day of soft diet (p<0.001) were significantly shorter for the laparoscopic surgery group than the open surgery group. The levels of CRP, IL-6, and VEGF rose significantly, and the concentration of IGFBP-3 fell significantly after both open and laparoscopic surgery. However, there were no significant differences in the preoperative and postoperative levels of CRP, IL-6, VEGF, and IGFBP-3 between the two groups. CONCLUSION: Our data suggest that both open and laparoscopic surgeries are accompanied by significant changes in IL-6, CRP, IGFBP-3, and VEGF levels. Acute inflammation markers and tumor stimulating factors may not reflect clinical benefits of laparoscopic surgery.