Terapêutica adjuvante na modulação da resposta imune no tratamento da doença periodontal: uma revisão de literatura / Adjuvant therapeutic in the modulation of the immune response in the treatment of periodontal disease: a literature review

Introdução: A Doença Periodontal tem caráter multifatorial, já que depende de condições microbiológicas, imunogenéticas e sistêmicas do hospedeiro. Representa inflamação crônica das estruturas de suporte e proteção dental. Desencadeia uma complexa estimulação imunológica, bem como a produção de citocinas inflamatórias, que mediam a destruição óssea e de tecido conjuntivo, provocando perda dental e complicações à distância. A compreensão da etiopatogênese, permitiu os conceitos de modulação, que referem-se às modificações dos aspectos danosos da resposta inflamatória. Objetivo: O presente artigo tem como objetivo realizar uma revisão dos estudos sobre as principais terapêuticas adjuvantes na modulação da resposta imune frente à doença periodontal. Revisão de Literatura: Foi realizada uma revisão da literatura, onde foram selecionados artigos científicos em inglês, publicados entre os anos 2005 a 2020, por meio das bases de dados PubMed e ScienceDirect. No decorrer das buscas, foram utilizadas as palavraschaves "Inflamation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Resultados e Conclusão: A literatura é bem promissora em relação à terapia de controle complementar da doença periodontal. Dessa forma, novas pesquisas nessa área podem trazer inúmeros beneficos aos pacientes, sendo, assim, um novo caminho para o contorno da resistência bacteriana(AU)

Introduction: Periodontal disease has a multifactorial character, depending on the host's microbiological, immunogenetic and systemic conditions. It represents chronic inflammation of dental support and protection structures. It triggers a complex immune stimulation, as well as the production of inflammatory cytokines, which mediate bone and connective tissue destruction, causing tooth loss and complications at a distance. The understanding of etiopathogenesis allowed the concepts of modulation, which refers to the modifications of the harmful aspects of the inflammatory response. This article has the escape of conducting a review of studies on the main mechanisms of modulation against periodontal disease. Objective: This article aims to rev iew the studies on the main modulation mechanisms in the face of periodontal disease. Literature Review: A literature review was carried out in which scientific articles were selected in English, published between 2005 and 2020, through the PubMed and ScienceDirect databases. During the searches, the keywords "Inflammation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Results and Conclusion: The literature is very promising with complementary control therapy for periodontal disease. Thus, new research in this area can bring countless benefits to patients, thus being a new way to bypass bacterial resistance(AU)

Short needling for knee osteoarthritis with blood stasis obstruction and its effect on serum inflammatory factors / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and its effect on serum levels of tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) between short needling (close-to-bone needling) and conventional acupuncture for knee osteoarthritis (KOA) with blood stasis obstruction.@*METHODS@#A total of 68 KOA patients with blood stasis obstruction were randomized into a short needling group (34 cases, 3 cases dropped off) and a conventional acupuncture group (34 cases, 3 cases dropped off). The same acupoints (Dubi [ST 35], Neixiyan [EX-LE 4], Binzhong [Extra], Liangqiu [ST 34], etc. on the affected side) were selected in the two groups. In the short needling group, short needling technique was adopted, the needles were slowly inserted and the needle bodies were shaken, thus gradually penetrated to the bone. In the conventional acupuncture group, conventional acupuncture was adopted, the needles were penetrated to the muscle. After qi-arrival, Dubi (ST 35) and Neixiyan (EX-LE 4), Zusanli (ST 36) and Liangqiu (ST 34) were connected with CMNS6-1 electronic acupuncture instrument, with disperse-dense wave, 2 Hz/10 Hz in frequency, the current intensity was based on patients' feeling, the needles were retained for 30 min, at the same time, the knee joint was irradiated for 30 min with a special electromagnetic wave apparatus in the two groups. Once every other day, 3 times a week for 4 weeks. Before and after treatment, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, knee joint pain visual analogue scale (VAS) score, inflammatory response related indexes (serum TNF-a, IL-1β, IL-6 and PGE2) and knee joint ultrasound were observed，and the clinical effect was evaluated in the two groups.@*RESULTS@#After treatment，the pain, stiffness, function scores and total scores of WOMAC were decreased as compared with those before treatment in the two groups (P<0.05), except for the pain score, the changes of above scores in the short needling group were greater than the conventional acupuncture group (P<0.05). After treatment, the VAS scores, serum levels of TNF-a, IL-1β, IL-6, PGE2 and knee joint synovium thickness, intra-articular effusion were decreased as compared with those before treatment in the two groups (P<0.05), the levels of TNF-a, IL-1β, IL-6 in the short needling group were lower than the conventional acupuncture group (P<0.05). The total effective rate in the short needling group was 87.1% (27/31), which was superior to 83.9% (26/31) in the conventional acupuncture group (P<0.05).@*CONCLUSION@#Short needling could improve the knee joint function, relieve the pain and inflammatory response, improve the knee joint synovium inflammatory response, reduce the knee joint intra-articular effusion for KOA patients, its effect is better than conventional acupuncture.

Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs / Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications associated with nephrotoxicity, especially when used chronically. Factors such as advanced age and comorbidities, which in themselves already lead to a decrease in glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity. The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition, interfering on arachidonic acid conversion into E2 prostaglandins E2, prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as vasodilators, increasing renal perfusion. This vasodilatation is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system works and that of the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically mediated. The second form of NSAID-induced AKI is acute interstitial nephritis, which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to chronic kidney disease (CKD). In patients without renal diseases, young and without comorbidities, NSAIDs are not greatly harmful. However, because of its dose-dependent effect, caution should be exercised in chronic use, since it increases the risk of developing nephrotoxicity.

Resumo Os anti-inflamatórios não esteroidais (AINEs) são medicamentos comumente utilizados, associados à nefrotoxicidade, sobretudo quando utilizados cronicamente. Fatores como idade avançada e comorbidades, que por si só já levam à diminuição da taxa de filtração glomerular, aumentam o risco de nefrotoxicidade dos AINEs. O principal mecanismo de ação dos AINEs é a inibição da enzima ciclooxigenase (COX), interferindo na conversão do ácido araquidônico em prostaglandinas E2, prostaciclinas e tromboxanos. Nos rins, as prostaglandinas atuam como vasodilatadoras, aumentando a perfusão renal. Essa vasodilatação atua como uma contrarregulação de mecanismos, como a atuação do sistema renina-angiotensina-aldosterona e do sistema nervoso simpático, culminando com uma compensação para assegurar o fluxo adequado ao órgão. O uso de AINEs inibe esse mecanismo, podendo causar lesão renal aguda (LRA). Altas doses de AINEs têm sido implicadas como causas de LRA, especialmente em idosos. A principal forma de LRA por AINEs é a hemodinamicamente mediada. A segunda forma de apresentação da LRA induzida por AINES é a nefrite intersticial aguda, que pode se manifestar com proteinúria nefrótica. O uso de AINEs em longo prazo pode ocasionar doença renal crônica (DRC). Nos pacientes sem doenças renais, jovens e sem comorbidades, os AINEs não apresentam grandes malefícios. Entretanto, por seu efeito dose-dependente, deve-se ter grande cautela no uso crônico, por aumentar risco de desenvolver nefrotoxicidade.

Proteínas Totales, Fosfatasa Alcalina, Prostaglandinas E2 y Lisozima como Biomarcadores Salivales en Pacientes Adultos con Periodontitis Crónica / Total Protein, Alkaline Phosphatase, Prostaglandin E2 and Lysozyme as Salivary Biomarkers in Patients with Chronic Periodontitis

RESUMEN: La periodontitis crónica es una inflamación de los tejidos que rodean y dan soporte a los dientes. Diversos biomarcadores químicos y pro inflamatorios están aumentados durante el transcurso de la enfermedad. El objetivo del estudio fue determinar los distintos niveles salivales de proteínas totales, fosfatasa alcalina, prostaglandina E2 (PGE2) y lisozima en pacientes con periodontitis crónica. Se obtuvieron muestras de saliva de 31 pacientes con periodontitis crónica y se realizó un estudio de serie de casos para la determinación cuantitativa de los biomarcadores. La concentración de proteínas totales se encontró por sobre los rangos de referencia en 22 pacientes, la actividad de la fosfatasa alcalina se vio aumentada en 9 pacientes y la concentración de PGE2 se vio por sobre los rangos de referencia en 30 pacientes. Las proteínas totales y PGE2 son biomarcadores salivales en estos pacientes con periodontitis, no así la fosfatasa alcalina y la lisozima.

ABSTRACT: Chronic periodontitis is an inflammation of tissue that surrounds and supports the teeth; during the course of the disease there is an increase of different chemical and pro-inflammatory biomarkers. The objective of the study was to determine different levels in saliva of total protein, alkaline phosphatase, lysozyme and prostaglandin E2 (PGE2) in patients with chronic periodontitis. We used saliva samples from 31 patients who had chronic periodontitis and the study was a case of series. Our results showed 22 patients with increased concentrations of protein concentration, nine patients with increased alkaline phosphatase and PGE2 concentration was above the reference range in 30 patients: The total protein and PGE2 are good salivary biomarkers in patients with periodontitis, but not the alkaline phosphatase and lysozyme.

Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish

ABSTRACT Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

A vigilância e o monitoramento das principais doenças crônicas não transmissíveis no Brasil - Pesquisa Nacional de Saúde, 2013 / Surveillance and monitoring of major chronic diseases in Brazil - National Health Survey, 2013

RESUMO: Objetivo: Descrever as principais doenças crônicas não transmissíveis (DCNT) no país segundo as informações coletadas em indivíduos de 18 anos ou mais de idade. Métodos: Foram utilizados dados da Pesquisa Nacional de Saúde (PNS), 2013, estudo transversal de base populacional. As proporções de cada DCNT foram calculadas e apresentadas segundo sexo, com intervalo de confiança de 95% (IC95%), com os valores absolutos. Resultados: Do total de entrevistados, 45,1% referiram ter pelo menos uma DCNT. A Região com maior prevalência de DCNT foi a Sul (52,1%). A hipertensão arterial apresentou a maior prevalência dentre as DCNT, com 21,4%, seguida por problema crônico de coluna (18,5%), depressão (7,6%), artrite (6,4%) e diabetes (6,2%). O grau de limitação intenso/muito intenso apresentou maiores prevalências para outra doença mental (37,6%) e acidente vascular cerebral (AVC) (25,5%). Conclusão: A melhoria dos serviços de saúde é indispensável para uma resposta efetiva à dupla carga de adoecimento de países de média e baixa renda.

ABSTRACT: Objective: To describe the major noncommunicable diseases (NCDs) in Brazil, according to the information collected from individuals aged 18 years or older. Methods: Data from the National Health Survey (PNS), 2013, a transversal population-based study, were used. The proportions of each NCD were calculated and presented according to sex, with a 95% confidence interval (95%CI), with the absolute values. Results: Of the total respondents, 45.1% reported presenting at least one NCD. The region with the highest prevalence of NCDs was the South (52.1%). Hypertension showed the highest prevalence among NCDs, with 21.4%, followed by chronic back problem (18.5%), depression (7.6%), arthritis (6.4%), and diabetes (6.2%). The intense/very intense degree of limitation showed a higher prevalence of other mental illnesses (37.6%) and cerebrovascular accident (25.5%). Conclusion: The improvement of health services is essential for an effective response to the double burden of illness in the middle- and low-income countries.

Culture of mouse peritoneal macrophages with mouse serum induces lipid bodies that associate with the parasitophorous vacuole and decrease their microbicidal capacity against Toxoplasma gondii

Lipid bodies [lipid droplets (LBs)] are lipid-rich organelles involved in lipid metabolism, signalling and inflammation. Recent findings suggest a role for LBs in host response to infection; however, the potential functions of this organelle in Toxoplasma gondii infection and how it alters macrophage microbicidal capacity during infection are not well understood. Here, we investigated the role of host LBs in T. gondii infection in mouse peritoneal macrophages in vitro. Macrophages cultured with mouse serum (MS) had higher numbers of LBs than those cultured in foetal bovine serum and can function as a model to study the role of LBs during intracellular pathogen infection. LBs were found in association with the parasitophorous vacuole, suggesting that T. gondii may benefit from this lipid source. Moreover, increased numbers of macrophage LBs correlated with high prostaglandin E2 (PGE2) production and decreased nitric oxide (NO) synthesis. Accordingly, LB-enriched macrophages cultured with MS were less efficient at controlling T. gondii growth. Treatment of macrophages cultured with MS with indomethacin, an inhibitor of PGE2 production, increased the microbicidal capacity against T. gondii. Collectively, these results suggest that culture with MS caused a decrease in microbicidal activity of macrophages against T. gondii by increasing PGE2 while lowering NO production.

Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-kappaB Pathways in Nasal Polyp-Derived Fibroblasts

PURPOSE: Interleukin 6 (IL-6) and IL-8 participate in the pathogenesis of chronic rhinosinusitis with nasal polyps, and their levels are increased by prostaglandin E2 (PGE2) in different cell types. The purposes of this study were to determine whether PGE2 has any effect on the increase in the levels of IL-6 and IL-8 in nasal polyp-derived fibroblasts (NPDFs) and subsequently investigate the possible mechanism of this effect. METHODS: Different concentrations of PGE2 were used to stimulate NPDFs at different time intervals. NPDFs were treated with agonists and antagonists of E prostanoid (EP) receptors. To determine the signaling pathway for the expression of PGE2-induced IL-6 and IL-8, PGE2 was treated with Akt and NF-kappaB inhibitors in NPDFs. Reverse transcription-polymerase chain reaction for IL-6 and IL-8 mRNAs was performed. IL-6 and IL-8 levels were measured byenzyme-linked immunosorbent assay (ELISA). The activation of Akt and NF-kappaB was evaluated by western blot analysis. RESULTS: PGE2 significantly increased the mRNA and protein expression levels of IL-6 and IL-8 in NPDFs. The EP2 and EP4 agonists and antagonists induced and inhibited IL-6 expression. However, the EP4 agonist and antagonist were only observed to induce and inhibit IL-8 expression level. The Akt and NF-kappaB inhibitors significantly blocked PGE2-induced expression of IL-6 and IL-8. CONCLUSIONS: PGE2 increases IL-6 expression via EP2 and EP4 receptors, and IL-8 expression via the EP4 receptor in NPDFs. It also activates the Akt and NF-kappaB signal pathways for the production of IL-6 and IL-8 in NPDFs. These results suggest that signaling pathway for IL-6 and IL-8 expression induced by PGE2 might be a useful therapeutic target for the treatment of nasal polyposis.

Study on analgesic and accompanying toxic and side effects of euodiae fructus based on clinical efficacy dose / 中国中药杂志

<p><b>OBJECTIVE</b>To observe and study the toxic and side effects of water extracts from Euodiae Fructus accompanied with its efficacy analgesic dose and its mechanism, in order to provide experimental basis for the correlation between its "efficacy-toxicity".</p><p><b>METHOD</b>Mice were randomly divided into 5 groups according to weight, namely the normal group, the voltaren group, and Euodiae Fructus water extracts high, middle and low dose groups. Mice were administered with drugs for consecutively seven days, abdominally injected with acetic acid at 90 min and treated with hot plates after the last administration to establish the pain model, in order to the toxic and side effects accompanied with the efficacy. Besides toxic symptoms in mice, activities of ALT and AST, and content of BUN and Cr in serum were detected to calculate indexes in livers and kidneys. The other part of serum was collected to detect the content and activities of PGE2, MDA, SOD, NO, NOS, GSH and GSH-PX in serum.</p><p><b>RESULT</b>Continuous oral administration of water extracts from Euodiae Fructus of efficacy dose could significantly decrease the frequency of writhe in mice and increase the hot plate pain threshold, with good dose-efficacy relationship. During the administration, mice showed such toxic symptoms as diarrhoea, idle move, dysphoria and slow growth of weight. The activities of both ALT and AST in serum and hepatic tissues were remarkably increased and the liver size remarkably increased, without notable chance in content of BUN and CR in serum. Kidney size increased in only the high dose group. The content and activities of PGE2, SOD, GSH, GSH-PX in serum notably decreased, where the content and activities of MDA, NO, NOS in serum increased. The above-mentioned changes gradually aggravated with the rise in dose. There was significant difference compared with the model group, showing 'dose-toxicity' relationship to certain extent.</p><p><b>CONCLUSION</b>Continuous oral administration of certain dose of water extracts from Euodiae Fructus to mice can generate the toxic and side effects in liver accompanying with the analgesic effect, and show dose-dependence relationship to some extent. Its analgesic mechanism is related to the reduction of PGE, content in blood, while its toxic mechanism is related to oxidative injury to some extent.</p>

Antiallodynic effects of vitamin C and vitamin E in chronic post-ischemia pain rat model / 대한마취과학회지

BACKGROUND: Recent research has shown that reactive oxygen species (ROS) play a significant role in the development and persistence of neuropathic pain through central sensitization via N-methyl-D-aspartate (NMDA) receptor activation. In the present study, we examined whether the intraperitoneal administration of vitamins C and E alone or together could alleviate mechanical allodynia in a chronic post-ischemia pain (CPIP) rat model. METHODS: Vitamins C and E were administered intraperitoneally to 48 male Sprague Dawley rats once per day for 3 days before hindpaw ischemia-reperfusion (I/R) injury was induced. On the third day, the CPIP rat model was produced by inducing ischemia in the left hindpaw by applying an O-ring for 3 h, followed by reperfusion. Three days after reperfusion, hindpaw mechanical allodynia was assessed by measuring the withdrawal response to von Frey filament stimulation. The rats were sacrificed immediately after behavioral testing to determine the phosphorylated NMDA receptor subunit 1 (pNR1) and extracellular-signal-regulated kinases (pERK) levels in the spinal cord. RESULTS: When the antioxidant vitamins C and E were administered intraperitoneally to CPIP rats, I/R injury-induced mechanical allodynia was attenuated, and pNR1 and pERK levels were decreased in the rat spinal cord. Additionally, the co-administration of both vitamins had an increased antiallodynic effect. CONCLUSIONS: The reduced phosphorylated NR1 and ERK levels indicate that vitamins C and E inhibit the modulation of spinal cord neuropathic pain processing. Co-administration of vitamins C and E had a greater antiallodynic effect.

Anti-inflammatory effects of Zingiber officinale roscoe involve suppression of nitric oxide and prostaglandin E2 production

Inflammation is a physiological response to injury and infection. However, chronic inflammation causes tissue damage and is a feature of most chronic diseases. Despite significant progress in developing therapies to target chronic inflammation over the years, almost all current therapies have serious side effects. The current investigation is to identify naturally-existing anti-inflammatory therapies with fewer side effects. The anti-inflammatory effects and mechanisms of action of extracts and fractions obtained using vacuum liquid chromatography [VLC] from ginger [Zingiber officinale] on the production of nitric oxide [NO] and prostaglandin E[2] [PGE[2]] were investigated. NO and PGE[2] production were induced by stimulating the mouse RAW264.7 monocyte/macrophage cell line with lipopolysaccharide [LPS]. Levels of NO and PGE[2] were deter-mined using the Griess method and enzyme linked sorbent assay [ELISA], respectively. Extracts of two Zingiber officinale species obtained with chloroform showed po-tent inhibitory effects on NO and PGE[2] production. The extracts had a higher potency than N[G]-nitro-L-arginine methyl ester [L-NAME], a known specific inducible nitric oxide synthase [iNOS] inhibitor and were comparable in their effects on PGE[2] with Indomethacin, a specific PGE[2] inhibitor. Further, we identified a fraction [F6] that had most potent inhibi-tory effects. The study shows that extract of Zingiber officinale have strong inhibitory effects on key pro-inflammatory mediators involved in chronic inflammation. Both the extracts and F6 had better inhibitory effects than established pharmaceutical inhibitors of NO and PGE[2]

A comparison of anti-inflammatory activities of green tea and grapefruit seed extract with those of microencapsulated extracts

We compared the effects of grapefruit seed extract (GFSE), green tea extract (GT) and their microencapsulated extract on anti-inflammatory activities in murine RAW 264.7 macrophages cell line. In order to protect the bioactive compounds in the extracts, they were microencapsulated with maltodextrin and H2O. Nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) protein expression and thiobarbiturate reactive substances (TBARS) were analyzed in LPS activated RAW 264.7 macrophages. The green tea extract at the range of 100-600 microg/mL inhibited NO, PGE2 production and iNOS protein expression without cytotoxicity in a dose-dependent manner. Grapefruit seed extract had strong inhibitory effects on NO and PGE production and iNOS protein expression at the range of 5-20 microg/mL without cytotoxicity. Microencapsulation of green tea extract had further inhibitory effects on NO and PGE2 production and on iNOS protein expression, whereas microencapsulated GFSE did not show any further inhibitory effects on these parameters. Taken together, our results suggest that GSFE might be a promising candidate for preventing inflammation related diseases, such as cardiovascular disease, cancer or diabetes, and the microencapsulation of green tea extract could improve its bioactivity.

Hiperostosis cortical neonatal: un efecto colateral de la administración prolongada de prostaglandinas E1 / Neonatal cortical hyperostosis: a side effect of prolonged prostaglandin E1 infusion

La infusión de prostaglandinas E1 (PGE1) es habitualmente administradapor tiempos cortos para mantener la permeabilidad del ductus arterioso en lactantes con cardiopatías congénitas. En pacientes a la espera de la cirugía cardíaca el tratamiento puede prolongarse. Pueden ocurrir efectos colaterales, en su mayoría reversibles con la supresión del tratamiento. La hiperostosis cortical es una complicación frecuente de la administración prolongada de PGE1.Objetivo: Determinar la incidencia y gravedad de la hiperostosis cortical en neonatos que requieren infusión prolongada de prostaglandinas E1. Se estudiaron 61 recién nacidos con cardiopatías congénitas admitidos en la Unidad de Cuidados Intensivos Neonatales de la Clínica Bazterrica, desde enero del 2006 hasta mayo del 2010. Cinco recién nacidos recibieron tratamiento prolongado con PGE1. Cuatro presentaron evidenciaclínica y radiológica de hiperostosis cortical con elevados niveles séricos de fosfatasa alcalina. Diagnosticar esta entidad permitirá evitar estudios complementarios innecesarios o la suspensión de la cirugía cardíaca.

Prostaglandin E1 (PGE1) infusion is usually administered for short periods to maintain patency of ductus arteriosus in infants with cyanotic heart disease. Prolonged therapy may be necessary while patients are awaiting surgical treatment. Several side effects occur at the onset of the treatment, most of them reversible once the treatment is discontinued. Cortical hyperostosis is a frequent complication of prolonged PGE1 infusion. Objective is to determine the incidence and severity of cortical hyperostosis in newborn requiring prolonged prostaglandin E1 infusion. 61 newborn babies were admitted in the Neonatal Intensive Care Unit at Bazterrica Clinic, Buenos Aires City, from January 2006 to May 2010. Five newborn received prolonged PGE1 therapy defined as a longer-than-one-week treatment. Four of them had radiologic evidence of cortical hyperostosis and elevated serum alkaline phosphatase. Accurate and rapid diagnosis of this condition is critical to reduce unnecessary laboratory tests and to avoid cardiac surgery canceling.

Effect of hypertonic saline and macrophage migration inhibitory factor in restoration of T cell dysfunction / 대한외과학회지

PURPOSE: Trauma-induced suppression of cellular immune function likely contributes to sepsis, multiple organ dysfunction syndrome and death. T cell proliferation decreases after traumatic stress. The addition of prostaglandin E2 (PGE2), which depresses immune function after hemorrhage and trauma, to T-cells decreases T-cell proliferation; and hypertonic saline restores PGE2-induced T-cell suppression. Recently, it has become apparent that macrophage migration inhibitory factor (MIF) plays a central role in several immune responses, including T-cell proliferation. However, the role of MIF in mediating hypertonic saline (HTS) restoration of T cell dysfunction is unknown. Therefore, we hypothesize that T cell immune restoration by HTS occurs, at least in part, by a MIF-mediated mechanism. METHODS: Jurkat cells were cultured in Roswell Park Memorial Institute media, at a final concentration of 2.5 x 106 cell/mL. The effects of HTS on T-cell proliferation following PGE2-induced suppression were evaluated in Jurkat cells: HTS at 20 or 40 mmol/L above isotonicity was added. MIF levels were determined by enzyme-linked immunosorbent assay and western blot analysis. RESULTS: PGE2 caused a 15.0% inhibition of Jurkat cell proliferation, as compared to the control. MIF levels decreased in PGE2-suppressed cells, as compared to the control. MIF levels were higher in cells treated with HTS than PGE2-stimulated cells. CONCLUSION: The role of HTS in restoring Jurkat cells proliferation suppressed by PGE2, at least in part, should be mediated through a MIF pathway.

Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model

BACKGROUND: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. METHODS: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. RESULTS: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. CONCLUSION: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

Apoptosis of the GABAergic interneuron in the dorsal horn of the chronic post-ischemic pain model / 대한마취과학회지

BACKGROUND: It is well known that the GABAergic inhibitory interneuronal system plays an important role in modulation of the noxious stimulation transmitted from the primary afferent input. Some studies have revealed the role that the GABA inhibitory interneuronal system plays in the modulation of pain transmission and the changes in the GABAergic interneurons that occur during the neuropathic pain. This study was conducted to evaluate the apoptosis of the GABAergic interneuron, which is assumed to contribute to neuropathic pain. METHODS: Male Sprague-Dawley rats weighing 290-310 g were used to create a CPIP (chronic post-ischemic pain) model, which was made by placing a tourniquet on the left hindpaw of the rats. The tourniquet was maintained for 3 hours, after which it was released to allow reperfusion. Thirty minutes prior to reperfusion, N-acetyl-L-cysteine (NAC group) or normal saline (control group) was injected. After reperfusion, mechanical allodynia and cold allodynia were measured. In addition, the release of cytochrome c into the cytosol was evaluated through western blot or immunohistochemistry of the spinal cord. RESULTS: Mechanical and cold allodynia developed and the number of GABA interneurons was reduced in the control group. Additionally, The cytochrome c from the GABA interneuron was released into the cytosol in the control group, but the amount released was reduced in response to treatment with NAC. CONCLUSIONS: The results of this study showed that the GABA interneuron in the Rexed laminae I, II released cytochrome c into the cytosol in CPIP neuropathic pain model, which is known to lead to apoptosis. However, treatment with N-acetyl-L-cysteine prevented this process.

Contralateral allodynia and central change in the chronic post-ischemic pain model rats / 대한마취과학회지

BACKGROUND: Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes including complex regional pain syndromes (CRPS). Underlying mechanisms for the development of such pain are still a matter of investigation. Several studies suggest that activation of the N-methyl-D-aspartate (NMDA) receptor is essential for central sensitization as a base for persistent pain. The aim is to assess whether alteration of NMDA receptor expression correlates with the contralateral allodynia in the chronic post-ischemia pain (CPIP) model rats representing CRPS-Type I. METHODS: Application of a tight-fitting tourniquet for a period of 3 hours before reperfusion produced CPIP in male Sprague-Dawley rats. The mechanical paw withdrawal thresholds to von Frey stimuli (using a dynamic plantar aesthesiometer) were measured as pain indicators in ipsilateral and contralateral hindpaws. Phosphorylation of the NMDA receptor 1 subunit (pNR1), assessed with Western blot, was measured in the contralateral L4-6 spinal cord. RESULTS: Ipsilateral and contralateral mechanical allodynia is present at 4 hours after reperfusion, peaked at 3 days, and continued for 7 days after reperfusion. The relative density of pNR1 of CPIP rats significantly decreased in the contralateral L4-6 spinal cord compared to baseline value (P < 0.05). There was significant correlation between paw withdrawal threshold and the relative density of pNR1 (ipsilateral; R2 = 0.75, P < 0.01, contralateral; R2 = 0.60, P < 0.01). CONCLUSIONS: These data suggest that pNR1 is correlated to the contralateral mechanical allodynia in CPIP rats.

The effects of superoxide dismutase on the expression of c-fos gene in the chronic post-ischemic pain model rats / 대한마취과학회지

BACKGROUND: Chronic post-ischemia pain (CPIP) model is reported to represent the complex regional pain syndrome type I. The administration of non-specific free radical scavengers reduced mechanical allodynia, but it is not evident which type of free radical is responsible for the development of CPIP. This study was investigated to elucidate the role of superoxide on the development of CPIP and the relationship with the expression of c-fos gene. METHODS: Male Sprague-Dawley rats weighing 290-310 g were housed in one cage with food and water ad libitum. CPIP model was made by placing a tourniquet on the left hindpaw of rats. The tourniquet maintained for 3 hours, then released to allow reperfusion. Thirty minutes before reperfusion, superoxide dismutase (SOD) or normal saline (control group) was injected. Mechanical allodynia and cold allodynia were measured at 1, 3, 5, 7, 14 and 28 days after reperfusion and compared. Also, spinal cord was harvested and the expression of c-fos gene was measured through the real time reverse transcription polymerase chain reaction. RESULTS: Superoxide dismutase reduced mechanical allodynia (1, 3, 5 and 14 day) and cold allodynia (1, 3 and 7 day) compared with control rats in left hindpaw. Expression of c-fos was significantly reduced in the SOD rats at the day 14 and 28 compare to the control rats. CONCLUSIONS: The administration of superoxide dismutase suppressed the allodynia and c-fos gene expression of CPIP model rats and it may be suggested that the superoxide has an important role in the development of CPIP.

Induction of labour with prostaglaudin E2 vaginal tablets in patients with previous caesarean section

The aim of this study is to determine the success rate of PGE2 induced labour after one caesarean section. A retrospective study was conducted on 61 patients in whom labour was induced with PGE2 vaginal tablets after one caesarean section at Dubai Hospital, UAE between January 1- December 31, 2003. The mean maternal age was 31.24 +/- years, the mean gestational age at induction of labour was 39.59 +/- weeks, gravidity ranged from 2 to 10. Fifty five patients [90.19%] were of low parity [Para 1 - 4] and six patients [9.8%] were of high parity [Para 5 and above]. The indications of induction of labour were post dated pregnancy, early labour pain, PROM, reduced number of maternally perceived foetal movements. The Bishop score was less than 6 in 45 patients [73.77%] i.e. cervix was unripe and was 6 or more in 16 patients [26.229%] i.e. cervix was ripe. The mean dose of PGE2 used was 3.565 +/- mg. Syntocinon augmentation was used in 7 patients 11.3%. Fourteen patients [22.95%] delivered by normal vaginal delivery, 46 [75.4%,] by repeat caesarean section and 1 patient by assisted vaginal delivery. The indications for repeat caesarean section were failure of descent of resenting part in 33 patients [71.74], foetal distress in 12 patients [26.08%] and hypertonic uterine contraction in 1 patient [2.17%]. The mean birth weight was 3.229 +/- gm. Apgar score at 1 minute was < 7 in 4 newborn babies [6.55%] but was > 7 in all other at 5 minutes. Women with one previous caesarean section can be offered induction of labour. The decision about the mode of delivery after caesarean section should take into consideration maternal preference and priorities, risk of uterine rupture and risks and benefits of caesarean section. However, larger studies needed for validation