Melissa Guerra Simões Pires

Phenolic Enriched Extract of Baccharis trimera Presents Anti-inflammatory and Antioxidant Activities

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) from B. trimera were evaluated. Using carrageenan-induced pleurisy as a model of acute inflammation, the phenolic extract at 15 mg/kg decreased significantly the analyzed parameters when compared to the carrageenan group (p < 0.05), thus showing potential anti-inflammatory activity. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH methods, respectively. Phenolic and ethyl acetate extracts presented higher antioxidant activity (p < 0.05) than ascorbic acid. The phenolic extract also showed the highest antioxidant potential in relation to the other extracts, thus suggesting that the antioxidant and anti-inflammatory activities were due to the presence of phenolic compounds.

An assessment of fructose-1,6-bisphosphate as an antimicrobial and anti-inflammatory agent in sepsis.

Tissue lesion mechanisms provoked by sepsis include the infectious process, inflammation, and cellular energy deficit. We chose to test fructose-1,6-bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial actions. Wistar rats were used and divided into three experimental groups: a control group (n=10), in which a capsule was introduced into the peritoneum of the animals; a septic group (n=10), in which a capsule containing non-sterile fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed that levels of leukocytes increased significantly in the septic group when compared to both the septic group treated with FBP and the control group. The blood cultures were 100% positive in both the septic group and the septic group treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory halo in the case of the antibiotic ampicillin, there was no such indication for FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that received the carrageenan injection. What is more, the sugar reduced the levels of ionic calcium in relation to the control group. This data proves the validity of using FBP in the treatment of sepsis, possibly due to its anti-inflammatory rather than antimicrobial action.

Treatment with N-methyl-d-aspartate receptor antagonist (MK-801) protects against oxidative stress in lipopolysaccharide-induced acute lung injury in the rat

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common syndromes that affect both clinical and surgical patients. This study describes the effects of a potent and specific N-methyl-d-aspartate receptor antagonist (MK-801) against oxidative stress in acute lung injury induced by intratracheal lipopolysaccharide (LPS) injection. This study was performed using male Wistar rats weighing 200-250g. Rats were randomly divided into four groups: control with isotonic saline instillation (n=6); LPS (100μg/100g of body weight) treated with saline (n=6); LPS treated with MK-801 (0.3mg/kg, intraperitoneally; n=6); LPS treated with MK-801 (0.3mg/kg, intratracheally; n=6). Twelve hours after the LPS instillation, rats were anesthetized and a bronchoalveolar lavage (BAL) was performed in order to determine the alveolar-capillary membrane alterations and the inflammatory infiltrate level. Blood and lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. The use of MK-801 decreased bronchoalveolar lavage fluid protein, LDH activity and inflammatory cells. Indeed, the treatment with MK-801 significantly attenuated lung oxidative damage and histopathologic alterations after LPS instillation. Our data provide the first experimental demonstration that MK-801 decreases oxidative stress and limits inflammatory response and alveolar disarray in lipopolysaccharide-induced acute lung injury.

N-Methyl-D-Aspartate Glutamate Receptor Blockade Attenuates Lung Injury Associated With Experimental Sepsis

BACKGROUND The aim of this study was to examine the effects of the N-methyl-D-aspartate receptor (NMDAR) channel blocker dizocilpine (MK-801) on lung injury in rats submitted to experimental sepsis induced by cecal ligation and perforation (CLP). METHODS Adult male Wistar rats submitted to CLP were given a single systemic injection of MK-801 (subcutaneously at 0.3 mg/kg) administered 4 or 7 h after CLP induction. Twelve hours after CLP BAL was performed to determine total cell count, protein content, and inflammatory parameters. In addition, lung was excised for histopathologic analyses and determination of NMDAR subunits content. In a separate cohort of animals mortality was recorded for 5 days. RESULTS Animals submitted to sepsis induced by CLP showed an increase in the content of NMDAR subunits NR1 and NR2A in the lung. Administration of MK-801 4 h after CLP induction resulted in a decrease in BAL fluid cellular content and decreased levels of proinflammatory cytokines. In addition, MK-801 decreased lung oxidative stress markers and histopathologic alterations and improved survival. CONCLUSIONS These findings indicate that NMDAR blockade might represent a promising novel therapeutic strategy for the treatment of sepsis and inflammatory disorders.

Intravenous toxicity of fructose-1,6-bisphosphate in rats

Fructose-1,6-bisphosphate (FBP) is a bisphosphorilated sugar with a protective action against events that lead to cellular damage. The toxicity of the drug was assessed when administered intravenously in Wistar rats in doses of between 250 and 4000 mg/kg. Ionic calcium, total calcium, inorganic serum phosphate and the electrocardiographic profile of these animals were assessed. The lethal dose (LD(50)) was established by means of PROBIT processing. There was no reduction in the levels of total calcium, with the administration of increased doses of FBP, although there was a significant reduction in the levels of ionic calcium in those groups that received 250 mg/kg and over. The serum phosphate showed a significant statistical increase in those groups that received 750 mg/kg and over. The LD(50) obtained in 24 h was 1068 mg/kg. Though it was not possible to elucidate the toxic mechanism of FBP, the electrocardiogram (ECG) showed that all the rats died of cardiac arrest.

Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes

INTRODUCAO E OBJETIVOS: Tem sido sugerido que o diabetes mellitus tipo 2 (DM2) e uma manifestacao da resposta inflamatoria. As principais drogas utilizadas no tratamento do DM2 sao as sulfonilureias e as biguanidas. O objetivo deste trabalho e demonstrar os efeitos moduladores na proliferacao de linfocitos causada pelos hipoglicemiantes orais (clorpropamida e metformina), in vitro e ex vivo. METODOS: Celulas mononucleares de sangue periferico foram isoladas de seres humanos por gradiente de centrifugacao. Os linfocitos T foram estimulados com fito-hemaglutinina (PHA) e hipoglicemiantes. RESULTADOS: Nos experimentos in vitro e ex vivo, mostramos a reducao da proliferacao celular quando do tratamento com drogas hipoglicemiantes orais. Quando as drogas foram utilizadas em combinacao, foi observado alto grau de citotoxicidade, tornando inviavel a analise do efeito imunomodulador. DISCUSSAO E CONCLUSAO: Mostramos que o diabetes, por si, pode reduzir significativamente a proliferacao celular quando estimulada por PHA, o que pode indicar que o paciente diabetico tem dificuldade em promover a eficiente resposta inflamatoria e que o uso de hipoglicemiantes pode piorar esta situacao.

Septic arthritis caused by Neisseria pharyngis in an elderly patient with knee prosthesis

Neisseria gonorrhoeae is one of the most plausible causes of bacterial arthritis in young individuals. Joint infection by Neisseria species considered commensals is rather unusual [1]. We herein describe a case of infectious arthritis caused by Neisseria pharyngis in an elderly patient with knee arthroplasty. The patient, an 86-year-old woman, was admitted to the Hospital because of chills and a 48-h arthritis of the left knee. Leukocytosis was present (25,200 cells/mm, 32% of young neutrophils). Erythrocyte sedimentation rate was 120 mm in the first hour. A left total knee arthroplasty had been carried out 10 years earlier due to osteoarthritis. No single debilitating factor (comorbidities, previous treatment with steroids, renal failure, hypogammaglobulinemia) was present. An arthrocentesis was promptly performed. The synovial fluid (SF) showed a purulent appearance. An open arthrotomy was subsequently carried out, yielding larger amounts of purulent SF. Oxacillin was started. A very high SF white cell count was seen (50,000 cells/mm, 85% neutrophils). The SF culture using Chocolate Polyvitex agar and Trypcase-soy agar ?5% sheep blood grew Neisseria sp. The knee radiogram demonstrated soft tissue edema; the prosthesis was properly placed. Three days of oxacillin was not helpful. At this time, a SF polymerase chain reaction (PCR) confirmed the presence of Neisseria pharyngis. The patient was treated with intravenous ceftriaxone plus clindamycin for 3 weeks and additional oral ciprofloxacin for 12 weeks. The outcome was favorable, and prosthesis replacement was not needed. A variety of Neisseria subspecies considered commensal (including Neisseria pharyngis) can colonize the throat. Eventually, these Neisseria subspecies turn out to be pathogenic due to hematological dissemination [2]. Septic arthritis caused by Neisseria subflava [3], Neisseria sicca [4], and Neisseria mucosa [5] have been reported. Neisseria mucosa knee arthritis occurred after a single sodium hyaluronate injection in a 78-year-old woman, according to a recent report [6]. Of interest, two cases of bacterial arthritis caused by Neisseria pharyngis were notified in England in 1991 [7] and 1993 [8]. Out of 1,158 cases of septic arthritis reported to the Public Health Laboratory Service from England and Wales over a 4-year period (January 1990 to December 1993), only one case attributable to Neisseria pharyngis was documented [9]. In the current case, some aspects are worthy of comment. Lack of response to oxacillin called attention to a non-staphylococcal etiology. The PCR following the positive SF culture for Neisseria sp. was essential to confirm the etiology. Why a non-gonococcal Neisseria caused such intense acute arthritis and a so high leukocyte counts in blood and the SF is an open question. The SF findings and the clinical response to treatment, as well as reports of other similar Neisseria sp causing septic arthritis [3–9], suggest that Neisseria pharyngis was M. Pires C. Z. X. de Freitas M. Franck H. L. Staub (&) Rheumatology Department, Faculty of Medicine, São Lucas Hospital, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga 6690/220, CEP: 90610-000 Porto Alegre, Brazil e-mail: reumatopucrs@gmail.com