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.

Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Abstract Objectives: Infection, inflammation and bone resorption are closely related events in apical periodontitis development. Therefore, we sought to investigate the role of cyclooxygenase (COX) in osteoclastogenesis and bone metabolism signaling in periapical bone tissue after bacterial lipopolysaccharide (LPS) inoculation into root canals. Methodology: Seventy two C57BL/6 mice had the root canals of the first molars inoculated with a solution containing LPS from E. coli (1.0 mg/mL) and received selective (celecoxib) or non-selective (indomethacin) COX-2 inhibitor. After 7, 14, 21 and 28 days the animals were euthanized and the tissues removed for total RNA extraction. Evaluation of gene expression was performed by qRT-PCR. Statistical analysis was performed using analysis of variance (ANOVA) followed by post-tests (α=0.05). Results: LPS induced expression of mRNA for COX-2 (Ptgs2) and PGE2 receptors (Ptger1, Ptger3 and Ptger4), indicating that cyclooxygenase is involved in periapical response to LPS. A signaling that favours bone resorption was observed because Tnfsf11 (RANKL), Vegfa, Ctsk, Mmp9, Cd36, Icam, Vcam1, Nfkb1 and Sox9 were upregulated in response to LPS. Indomethacin and celecoxib differentially modulated expression of osteoclastogenic and other bone metabolism genes: celecoxib downregulated Igf1r, Ctsk, Mmp9, Cd36, Icam1, Nfkb1, Smad3, Sox9, Csf3, Vcam1 and Itga3 whereas indomethacin inhibited Tgfbr1, Igf1r, Ctsk, Mmp9, Sox9, Cd36 and Icam1. Conclusions: We demonstrated that gene expression for COX-2 and PGE2 receptors was upregulated after LPS inoculation into the root canals. Additionally, early administration of indomethacin and celecoxib (NSAIDs) inhibited osteoclastogenic signaling. The relevance of the cyclooxygenase pathway in apical periodontitis was shown by a wide modulation in the expression of genes involved in both bone catabolism and anabolism.

COX-2 Inhibitors in Dental Pain Management / Inhibidores de la COX-2 en el Tratamiento del Dolor Dental

ABSTRACT: Pain is a major symptom in many dental procedures. Studies show consistently that pain, including dental pain, is not effectively treated; management of pain is a critical and challenging component in dentistry. Improvement and efficacy on the treatment depends on knowing which treatments are the most effective. Knowing how well an analgesic works and its associated adverse effects is fundamental to clinical decision. The aim of this review is to provide information to the dentistry field on the treatment of dental pain specifically with COX-2 inhibitors providing a useful guide to dentist on controlling pain. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic agents in surgical outpatients. Major limitations of NSAIDs are their gastrointestinal (GI) adverse events (perforation, ulceration, and bleeding), impairment of hemostatic function, and renal failure (with long-term therapy). A new class of NSAIDs, COX2 selective inhibitors (Coxibs), have been developed with the aim of reducing the GI adverse events of traditional NSAIDs while maintaining their effective anti-inflammatory and analgesic properties.

RESUMEN: El dolor es un síntoma principal en muchos procedimientos dentales. Los estudios demuestran consistentemente que el dolor, incluido el dolor dental, no se trata de manera efectiva; el manejo del dolor es un componente crítico y desafiante en odontología. La mejora y la eficacia en el tratamiento depende de saber qué tratamientos son los más efectivos. Saber qué tan bien funciona un analgésico y sus efectos adversos asociados es fundamental para la decisión clínica. El objetivo de esta revisión es proporcionar información al campo de la odontología sobre el tratamiento del dolor dental específicamente con los inhibidores de la COX-2, proporcionando una guía útil para el control del dolor por parte del dentista. Por lo tanto, los fármacos antiinflamatorios no esteroideos (AINE) son los agentes analgésicos más comúnmente prescritos en pacientes ambulatorios quirúrgicos. Las principales limitaciones de los AINE son los eventos adversos gastrointestinales (perforación, ulceración y hemorragia), deterioro de la función hemostática e insuficiencia renal (con terapia a largo plazo). Una nueva clase de AINE, los inhibidores selectivos de la COX-2 (Coxibs), se han desarrollado con el objetivo de reducir los eventos adversos gastrointestinales de los AINE tradicionales mientras se mantienen sus propiedades antiinflamatorias y analgésicas efectivas.

New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2 / 中国天然药物

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.

New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2 / 中国天然药物

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.

The role of potassium channels in the endothelial dysfunction induced by periodontitis

Abstract Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Material and methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.

Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi) / Acetilcolina produz contrações mediadas pela via da ciclooxigenase em vasos arteriais da rã chileno (Calyptocephalella gayi)

Abstract Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.

Resumo Estudos feitos em peixes marinhos (I. conceptionis e G. laevifrons) têm demostrado que a indometacina bloqueia a contração arterial mediada por acetilcolina (ACh). O objetivo do presente estudo foi avaliar o efeito da via da ciclooxigenase na contração induzida por ACh em vasos arteriais da rã chilena Calyptocephalella gayi. Foram dissecadas regiões das artérias pulmonares (PA), dorsal (DA), mesentérica (MA) e ilíaca (IA) de seis espécimes adultos e realizados estudos de tensão isométrica utilizando curvas dose-resposta (CDR) de ACh (10-13 a 10-3 M) na presença de um antagonista muscarínico (atropina, 10-5 M) e um inibidor das ciclooxigenases (indometacina, 10-5 M). Todas as artérias evidenciaram uma resposta vasoconstritora mediada por ACh. Esta resposta vasoconstrictora foi suprimida na presença de atropina nas artérias DA, MA, IA e atenuada na PA. A indometacina suprimiu a vasoconstrição na artéria MA e atenuou a resposta nas artérias PA, DA e IA. Tal como os peixes marinhos, a C. gayi tem um padrão de vasoconstrição mediado por Ach que é regulado pelos receptores muscarínicos e pela ciclooxigenase. Estes resultados sugerem a conservação dos mecanismos vasoconstrictores mediados por ACh→COX em peixes e rãs.

Inhibition of cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) by D-005 (A lipid extract of Acrocomia crispa fruits) / [Inhibición de la ciclooxigenasa (COX) y la 5-lipooxigenasa (5-LOX) por el D-005 (extracto lipidico del fruto de la Acrocomia crispa)

This study was aimed to investigate whether the a lipid extract from Acrocomia crispa fruits (D-005) inhibits COX and 5-LOX enzyme activities in vitro. This study demonstrates that D-005 inhibits markedly and in a dose dependent manner COX-2 and 5-LOX activities. The dual inhibition of COX-2 and 5-LOX supports further research on the potential anti-inflammatory effect of D-005.

El objetivo de este estudio fue investigar si el extracto lipídico de los frutos de Acrocomia crispa (D-005) inhibe in vitro las actividades de las enzimas COX y 5-LOX. Este estudio demuestra que el D-005 inhibe marcadamente y de manera dosis dependiente las actividades de la COX-2 y 5-LOX. La inhibición dual de la COX-2 y 5-LOX soportan futuras investigaciones sobre el potencial efecto anti-inflamatorio del D-005.

Individualized ibuprofen treatment using serial B-type natriuretic peptide measurement for symptomatic patent ductus arteriosus in very preterm infants / 소아과

PURPOSE: Plasma level of B-type natriuretic peptide (BNP), an emerging, sensitive, and specific biomarker of hemodynamically significant patent ductus arteriosus (PDA), rapidly decreases in infants receiving cyclooxygenase inhibitors for ductal closure. We investigated the usefulness of serial BNP measurement as a guide for individual identification of early constrictive responses to ibuprofen in preterm infants with symptomatic PDA (sPDA). METHODS: Before March 2010, the standard course of pharmacological treatment was initiated with indomethacin (or ibuprofen) and routinely followed by 2 additional doses at intervals of 24 hours. After April 2010, individualized pharmacological treatment was used, starting with the first dose of ibuprofen and withholding additional ibuprofen doses if the BNP concentration was <600 pg/mL and clinical symptoms of PDA improved. RESULTS: The BNP-guided group received significantly fewer doses of ibuprofen than the standard group did during the first course of treatment and the entire study period. The need for further doses of cyclooxygenase inhibitors and for surgical ligation was not significantly different between the 2 groups. No significant differences were seen in clinical outcomes and/or complications related to sPDA and/or pharmacological treatment. CONCLUSION: Individualized BNP-guided pharmacological treatment may be used clinically to avoid unnecessary doses of cyclooxygenase inhibitors without increasing the ductal closure failure and the short-term morbidity related to sPDA.

Immediate postoperative evaluation of enteric anastomosis after the use of meloxicam in rats

ABSTRACT PURPOSE : To compare ileal anastomoses in the immediate postoperative healing period after meloxicam use. METHODS: Forty two male Wistar rats were randomly divided into two groups of 21, COX and control group. To COX meloxicam in combination with morphine was given in 3 days period. Control group received only morphine during the same period. Each group was divided into three sub-groups of 7, which were euthanized at 5, 10, and 21 days postoperatively. Comparison was based in histological evaluation of collagen type I and III using sirius red, immunohistochemical through vascular endothelial growth factor and matrix metalloproteinase-9. RESULTS: Healing process in scheduled periods did not show significant differences (p>0.05) between the COX and control groups during any of the periods. CONCLUSION: The use of meloxicam in the postoperative period following ileal anastomosis did not affect healing.

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits

PURPOSE: To investigate the efficacy of intralesional 20% aspirin injection for treatment of experimental peritoneal endometriosis. Methods: Peritoneal endometriosis was experimentally induced in forty adult nulligravid female rabbits. On day 30 post-endometriosis induction, rabbits were randomly divided to assess early (10 days) and late (20 days) effects of intralesional injection of physiological saline solution (control groups) in comparison to intralesional injection of 20% bicarbonate aspirin solution (experimental groups) as follows: control group 1 (10 days, n=10); control group 2 (20 days, n=10); experimental group 3 (10 days, n=10); experimental group 4 (20 days, n=10). Resected tissues, including endometriosis foci, were qualitatively (general morphology and signs of inflammatory cells infiltrate, necrosis and apoptosis) and quantitatively (remaining endometriosis area) assessed by histopathological analysis. Results: Extensive necrosis, hemorrhage, apoptosis, and fibrosis were observed in the experimental groups 3 and 4. Groups 1 and 2 presented typical endometrial tissue cysts, respectively. Groups 3 and 4 showed sparse endometrial tissue foci and no endometrial tissue, respectively. Quantitative analysis revealed that aspirin-treated groups 3 and 4 had significantly (p<0.05) smaller remaining endometriosis area, compared to control groups 1 and 2. Conclusion: Intralesional 20% aspirin injection caused total destruction of peritoneal endometriosis foci in rabbits.

Prophylactic intravenous ketorolac for prevention of intraventricular hemorrhage in preterm infants ? 32 weeks and < 1500 grams: A double-blind, randomized, placebo-controlled trial

@#<p style="text-align: justify;">Intraventricular hemorrhage (IVH) remains an important cause of morbidity and mortality in Very Low Birth Weight (VLBW) infants. Since 2004, Indomethacin, which is effective in preventing IVH, has been removed from the Philippine market. Ketorolac is a nonselective cyclooxygenase inhibitor which is structurally-related and of equal potency to Indomethacin.<br /><strong>OBJECTIVE:</strong> This study aims to determine if prophylactic ketorolac compared to placebo will decrease IVH and its associated morbidities among preterm neonates.<br /><strong>METHODS:</strong> We conducted a double-blind, randomized, placebo-controlled trial among neonates born in a tertiary government university hospital. Newborns with gestational age ?32 weeks and birth weight <strong>RESULTS:</strong> A total of 134 infants were included in this study. There was no difference in the proportion of infants who developed IVH between the ketorolac and placebo groups (46% vs. 45%). The mean serum creatinine levels were significantly higher in the ketorolac group (1.15 ± 0.69 vs 0.79 ±0.38; p=0.002). The rates of death, sepsis, necrotizing enterocolitis, bleeding, platelet counts of <50,000/mm3, mean urine output and the lengths of hospital stay were similar in the two groups.<br /><strong>CONCLUSION:</strong> Prophylactic intravenous ketorolac was ineffective in preventing IVH among preterm infants. Ketorolac cannot be recommended for the prevention of IVH.</p>

Analgesic and anti-inflammatory effects of UP1304, a botanical composite containing standardized extracts of Curcuma longa and Morus alba / 中西医结合学报

<p><b>OBJECTIVE</b>Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema.</p><p><b>METHODS</b>A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation.</p><p><b>RESULTS</b>Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively.</p><p><b>CONCLUSION</b>Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.</p>

Efeito antimicrobiano da indometacina no biofilme periodontal: estudo em ratos / Antimicrobial effect of indomethacin on periodontal biofilm: study in rats

Introdução: A doença periodontal é uma doença de caráter multifatorial que se desenvolve em decorrência da interação do biofilme bacteriano com a resposta imuno-inflamatória do hospedeiro que pode ser modulada por fatores sistêmicos e ambientais. Objetivo: o presente estudo teve como objetivo avaliar a ação antimicrobiana do anti-inflamatório não esteroidal indometacina sobre o biofilme retido em ligaduras inseridas subgengivalmente para indução de periodontite experimental em ratos. Método: assim, 20 animais foram divididos aleatoriamente em um dos grupos: grupo Indometacina (n=10); grupo água destilada (n=10). Os animais receberam gavagem diária da medicação (5 mg/kg indometacina) ou de água destilada (2 ml), durante 7 dias. As ligaduras ao redor dos dentes foram coletadas e o biofilme foi dispersado, diluído em 10-1, 10-2 e 10-3, semeado em ágar sangue e as placas foram cultivadas em anaerobiose durante 4 dias. As quantificações foram realizadas a partir da contagem das unidades formadoras de colônias (UFC) totais pelo programa Colony counter aplicativo para androide, caracterizadas pela presença de bactérias aeróbias e aeróbias facultativas relacionadas ao processo de saúde, e pela contagem manual de UFC grandes, que melhor caracterizam as bactérias anaeróbias relacionadas ao processo de doença. Resultado: constatou-se um número significativamente maior de UFC grandes no grupo indometacina quando comparado ao grupo água (p=0,004) e um número significativamente menor de UFC totais no grupo indometacina quando comparado ao grupo água (p=0,0013). Conclusão: dentro dos limites do presente estudo pôde-se concluir que a indometaciana agrava o processo infeccioso periodontal devido ao crescimento de UFC anaeróbias e redução de UFC facultativas.

Introduction: Periodontal disease is a multifactorial disease the develop as a result of the interaction of the bacterial biofilm and the immune-inflammatory response of the individual, which, in its turn, is modulate by systemic and environmental factors. Objective: This study aimed to evaluate the antimicrobial effect of indomethacin, a non-steroidal anti-inflammatory, on the biofilm retained in ligatures inserted in the subgingival region to induce experimental periodontitis in rats. Method: 20 animals were randomly assigned to one of the groups: Indomethacin (n = 10); distilled water (n = 10). The animals received daily gavage of drugs (5 mg / kg indomethacin) or distilled water (2 ml) for 7 days. The ligatures around the teeth were collected and the biofilm was dispersed, diluted 10-1, 10-2 and 10-3, seeded in blood agar and the plates were grown anaerobically for 4 days. The measurements were carried out from the counting of total colony forming units (CFU) by Colony counter application program for android, characterized by the presence of facultative aerobic and aerobic bacteria related health process, and the manual counting of large CFU, which better characterized the anaerobic bacteria-related disease process. Result: it was found a significantly higher number of large CFU in indomethacin group compared to the water group (p = 0.004) and a significantly lower number of total CFU in the indomethacin group compared to the water group (p = 0.0 013). Conclusion: within the limits of this study it was concluded that the indomethacin worsens periodontal infectious process due to the growth of anaerobic CFU and the reduction of facultative CFU.

New COX-2 Inhibitors / 대한내과학회지

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation. There are two kinds of NSAID classified according to the selectivity of COX-2 inhibition: non-selective NSAIDs and cyclooxygenase (COX)-2 inhibitors. Non-selective NSAIDs have a high incidence of gastrointestinal and bleeding-associated adverse events, while COX-2 inhibitors are safer in terms of these events. However, COX-2 inhibitors are thought to cause increased cardiovascular events. The COX-2 inhibitors rofecoxib and valdecoxib were withdrawn from the market over safety concerns. Three COX-2 inhibitors are now available in South Korea after the recent approval of etoricoxib and polmacoxib for osteoarthritis patients. After reviewing the history of and recent studies about the safety of COX-2 inhibitors, physicians should find new uses for old drugs.

Histological changes caused by meclofenamic acid in androgen independent prostate cancer tumors: evaluation in a mouse model

ABSTRACT Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.

Evaluation of protein undernourishment on the condylar process of the Wistar rat mandible correlation with insulin receptor expression

The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. Objectives The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. Material and Methods The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. Results The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. Conclusions Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs. .

Clinical characteristics and cardiac hemodynamic changes of patent ductus ateriosus in preterm infants / 中华儿科杂志

<p><b>OBJECTIVE</b>To study clinical characteristics and evaluate cardiac hemodynamic changes in premature infants with patent ductus ateriosus (PDA).</p><p><b>METHOD</b>One hundred and five infants born at ≤ 34 weeks' gestational age (GA) and ≤2 000 g birth weight (BW) were prospectively enrolled, including 63 males and 42 females, and the mean GA was (31. 1 ± 1.9) weeks and BW (1 401 ± 314) g. Echocardiography was done to detect hemodynamically significant PDA (hsPDA) and to evaluate left ventricular function at 2, 3, 5 and 7 d respectively after birth. On the basis of clinical symptoms and echocardiographic outcome, all the cases were divided into 3 groups: hsPDA group (n = 34), non-hsPDA (nhsPDA) group (n = 44) and non-PDA (nPDA) group (n = 27) to survey and compare general conditions, DA diameter, shunt direction, left ventricular function and complications.</p><p><b>RESULT</b>The hsPDA group had smaller GA ((30. 5 ± 2. 1) vs. (31. 6 ± 1. 6) weeks, P = 0. 01) and greater proportion of pulmonary surfactant use and mechanical ventilation (2, 3, 5 d of birth) than the nhsPDA and the nPDA group (χ2 = 11. 62, 14. 95, 12. 73, 1:1. 59, P = 0. 00; 0. 00, 0. 01, 0. 01). Univariate and multivariate Logistic regression analysis indicated that the average length of stay (ALOS) was correlated with hsPDA (F =3. 52 and P =0. 03, OR 1. 03 and P =0. 02). The ALOS was longer in the hsPDA group than in the nhsPDA and the nPDA group ((39 ±23)vs. (30 ± 16)and(29 ±13) d, P =0.02, 0.03). There was no significant.difference in rates of mortality/giving-up of treatment among the three groups (5. 9% (2/34)vs. 0 (0/44) and 3. 7% (1/27), χ2 = 5. 26, P = 0. 06). Diastolic blood pressure and mean blood pressure were significantly lower in the hsPDA group than in the other two groups (P all <0. 05) at 2, 3 and 5 days after birth and the pulse pressure was found significantly higher in the hsPDA group than in the nPDA group at 2 d after birth. Univariate and multivariate Logistic regression analysis demonstrated that hsPDA was correlated significantly with neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD) (χ2 =7. 34 and 7. 39, P = 0. 02 and 0. 02; OR = 3. 46 and 4. 01, P = 0. 04 and 0. 02). Premature infants with hsPDA had normal left ventricular fractional shortening (FS) and left ventricular ejection fraction (LVEF), although the cardiac output (CO) of left ventricle increased significantly(F = 6. 93, P <0. 01) within seven days of birth. There was no significant difference in cardiac hemodynamic parameters among closed group of hsPDA group, nhsPDA group and nPDA group simutaneously reexamined at 7th day after birth. The CO was extremely significantly different among premature infants who had different GAs and BWs. The lower the GAs and the BWs, the lower the value of CO(F =5. 16 and 14. 87, P all <0. 01). The DA diameter was reduced much more dramatically after ibuprofen treatment than before in hsPDA group(t = 5. 58, P <0. 01).</p><p><b>CONCLUSION</b>The GA, PS use and mechanical ventilation were probably associated with hsPDA. The mean blood pressure and diastolic blood pressure were decreased and pulse pressure was increased in preterm infants with hsPDA that correlated significantly with ALOS, NRDS and BPD. In addition, increased CO values were found in hsPDA group. Oral ibuprofen administered to preterm infants for hsPDA at > 24 h of life promoted ductal closure.</p>

Occurrence of anti-Toxoplasma gondii antibodies in meat and dairy goat herds in Rio Grande do Norte, Brazil / Ocorrência de anticorpos anti-Toxoplasma gondii em rebanhos caprinos de corte e leiteiros do Rio Grande do Norte, Brasil

Toxoplasmosis is caused by Toxoplasma gondii, which is the main causative agent of abortion in small ruminants. Goats are among the animals that are most susceptible to this protozoon, and the disease that it causes leads to significant economic losses and has implications for public health, since presence of the parasite in products of goat origin is one of the main sources of human infection. Because of the significant economic impact, there is an urgent need to study the prevalence of T. gondii infection among goats in Sertão do Cabugi, which is the largest goat-producing region in Rio Grande do Norte. In the present study, the ELISA assay was used to test 244 serum samples from nine farms, located in four different municipalities in the Sertão do Cabugi region, which is an important goat-rearing region. The results showed that the prevalence of anti-T. gondii antibodies was 47.1% and that there was a significant association between positivity and the variables of age (≥ 34 months), location (Lajes, Angicos and Afonso Bezerra) and farm (all the farms). The avidity test was applied to all the 115 ELISA-positive samples to distinguish between acute and chronic infection. One hundred and three samples (89.6%) displayed high-avidity antibodies, thus indicating that most of the animals presented chronic infection, with a consequent great impact on the development of the goat production system and a risk to human health.

A toxoplasmose é causada pelo Toxoplasma gondii, principal agente causador de aborto em pequenos ruminantes. Os caprinos são uns dos animais mais suscetíveis a esse protozoário, levando a perdas econômicas significativas e implicações para a saúde pública, uma vez que a presença do parasito em produtos de origem caprina é uma das principais fontes de infecção humana. Devido ao impacto econômico significativo torna-se urgente estudar a prevalência da infecção, pelo T. gondii, entre caprinos do Sertão do Cabugi, a maior região produtora de caprinos no Rio Grande do Norte. O presente estudo utilizou o ELISA para testar 244 amostras de soro de 9 fazendas, situadas em 4 diferentes cidades na região do Sertão do Cabugi; uma importante região de criação de cabras. Os resultados mostraram uma prevalência de 47,1% para anticorpos anti- T. gondii e uma significativa associação entre a positividade e as variáveis idade (≥ 34 meses), localização (Lajes, Angicos e Afonso Bezerra e propriedade (todas as fazendas). O teste de avidez foi aplicado a todas as 115 amostras positivas pelo ELISA para discriminar entre infecção aguda e crônica. Cento e três amostras (89,6%) apresentaram anticorpos de alta avidez; indicando que a maioria dos animais estavam em infecção crônica, gerando um grande impacto sobre o desenvolvimento do sistema de produção em cabras e um risco para a saúde humana.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.