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.

Fructose-1,6-bisphosphate inhibits in vitro and ex vivo platelet aggregation induced by ADP and ameliorates coagulation alterations in experimental sepsis in rats.

Sepsis is a systemic response to an infection that leads to a generalized inflammatory reaction. There is an intimate relationship between procoagulant and proinflammatory activities, and coagulation abnormalities are common in septic patients. Pharmaceutical studies have focused to the development of substances that act on coagulation abnormalities and on the link between coagulation and inflammation. Fructose-1,6-bisphosphate (FBP) is a high-energy glycolitic metabolite that in the past two decades has been shown therapeutic effects in great number of pathological situations, including sepsis. The aims of this study were to assess the effects of FBP on platelet aggregation in vitro and ex vivo in healthy and septic rats and evaluate the use of FBP as a treatment for thrombocytopenia and coagulation abnormalities in abdominal sepsis in rat. FBP inhibited platelet aggregation (P < 0.001) in vitro in healthy rats from the smallest dose tested, 2.5 mM, in a dose-dependent manner. The mean effective dose calculated was 10.6 mM. The highest dose tested, 40 mM, completely inhibited platelet aggregation (P < 0.001) induced by ADP. Platelet aggregation in plasma from septic rats was inhibited only with higher doses of FBP, starting from 20 mM (P < 0.001). The calculated mean effective dose was 19.3 mM. Ex vivo platelet aggregation in septic rats was significantly lower (P < 0.05) than healthy rats and the treatment with FBP, at the dose of 2 g/kg, diminished the platelet aggregation at the extension of 27% (P < 0.001), suggesting that FBP is a potent platelet aggregation inhibitor in vivo. Moreover, treatment with FBP 2 g/kg prevented thrombocytopenia (P < 0.001), prolongation of prothrombin and partial thromboplastin time (P < 0.001), but not fibrinogen, in septic rats. The most important findings in this study are that FBP is a potent platelet aggregation inhibitor, in vitro and ex vivo. It presents protective effects on coagulation abnormalities, which can represent a treatment against DIC. The mechanisms for these effects remain under investigation.

Evaluation of inspiratory pressure in children with enlarged tonsils and adenoids.

UNLABELLED: Children with enlarged tonsils and adenoids usually present breathing abnormalities such as snoring, mouth breathing and sleep apnea. It is known that upper airway obstruction and consequent mouth breathing may result in pulmonary diseases. AIM: The goal of this preliminary study was to evaluate the inspiratory pressure in children with upper airway obstruction due to enlarged tonsils. STUDY DESIGN: Clinical with transversal cohort. MATERIAL AND METHOD: We evaluated 37 children (4-3 years old, female/male) with enlarged tonsils who would be submitted to a T&A surgery in the Department of Otolaryngology, Medical School, University of Sao Paulo, from October 2002 to March 2003. The control group comprised 28 children without tonsillar disease submitted to the same tests. Inspiratory pressure was obtained using a manometer and vacuum meter. RESULTS: We could observe lower inspiratory pressures in children with upper airway obstruction. The mean of inspiratory pressure in the upper airway obstruction group was 14.607 cm/H2O and in the control group was of 27.580 cm/H2O. CONCLUSIONS: Enlarged tonsils and adenoids were associated with poor inspiratory pressure, resulting in increased breathing effort and work of the involved muscles.

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.

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.

Anti-inflammatory and immunomodulatory effects of Ulomoides dermestoides on induced pleurisy in rats and lymphoproliferation in vitro.

The following study aimed to evaluate, in vitro and in vivo, the anti-inflammatory effect of Ulomoides dermestoides, a beetle commonly used as a remedy for a variety of diseases including respiratory disorders and asthma. We used an acute inflammation model of injury, injection of carrageenan into the pleural cavity of rats. The rats were treated intraperitoneally with the aqueous extract of U. dermestoides 8 and 16 mg/kg. The exudate volume, protein concentration, polymorphonuclear leukocytes (PMNs) and total leukocyte were measured. The peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy subjects and we investigated the immunomodulatory and cytotoxic effect of aqueous extract of U. dermestoides. In conclusion, in vitro we observed a non-cytotoxic effect and antiproliferative activity on the dose of 12.5 mg/dL. In vivo, this paper clarifies the great clinical relevance of the aqueous extract of U. dermestoides in elucidating its role as an anti-inflammatory agent.

Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2 / Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes

INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulated by phytohemagglutinin (PHA) and oral hypoglycemic drugs. RESULTS: In both in vitro and ex vivo experiments, there was a reduction in cell proliferation after treatment with oral hypoglycemic drugs. When both drugs were used in combination, a high level of cytotoxicity was observed, which made analysis of immunomodulatory effects unfeasible. DISCUSSION AND CONCLUSION: We demonstrated that diabetes itself may reduce cell proliferation significantly when stimulated by PHA, which may indicate that diabetic patients have difficulties in promoting an efficient inflammatory response. Moreover, the use of oral hypoglycemic drugs may aggravate this situation.

INTRODUÇÃO E OBJETIVOS: Tem sido sugerido que o diabetes mellitus tipo 2 (DM2) é uma manifestação da resposta inflamatória. As principais drogas utilizadas no tratamento do DM2 são as sulfonilureias e as biguanidas. O objetivo deste trabalho é demonstrar os efeitos moduladores na proliferação de linfócitos causada pelos hipoglicemiantes orais (clorpropamida e metformina), in vitro e ex vivo. MÉTODOS: Células mononucleares de sangue periférico foram isoladas de seres humanos por gradiente de centrifugação. Os linfócitos T foram estimulados com fito-hemaglutinina (PHA) e hipoglicemiantes. RESULTADOS: Nos experimentos in vitro e ex vivo, mostramos a redução da proliferação celular quando do tratamento com drogas hipoglicemiantes orais. Quando as drogas foram utilizadas em combinação, foi observado alto grau de citotoxicidade, tornando inviável a análise do efeito imunomodulador. DISCUSSÃO E CONCLUSÃO: Mostramos que o diabetes, por si, pode reduzir significativamente a proliferação celular quando estimulada por PHA, o que pode indicar que o paciente diabético tem dificuldade em promover a eficiente resposta inflamatória e que o uso de hipoglicemiantes pode piorar esta situação.

Physiopathological studies in septic rats and the use of fructose 1,6-bisphosphate as cellular protection.

OBJECTIVE: The aim of this research project was to test the ability of fructose 1,6-bisphosphate (FBP), which has anti-inflammatory effects and maintains cellular energy levels, to inhibit the septic process in an experimental model in rats. DESIGN: Prospective, controlled animal trial. SETTING: Research laboratory. SUBJECTS: Fed male Wistar rats. INTERVENTIONS: Three experimental groups were formed for the test: control group, untreated septic group, and septic group treated with FBP (500 mg/kg). MEASUREMENTS AND MAIN RESULTS: In the control group, there were no deaths; in the untreated septic group, the mortality rate was 100% within 15 hrs; in the septic group treated with FBP, the mortality rate reached 20% within 15 hrs. The blood cell tests revealed that concentrations of hematocrit, leukocytes, monocytes, and immature cells increased significantly in the untreated septic group compared with both the FBP-treated septic group and the control group. The histologic lesions verified in the heart, lungs, liver, and kidneys of septic animals were smaller and even absent in those treated with FBP. CONCLUSION: FBP reduced the mortality rate provoked by experimental sepsis and ameliorated hematologic and histologic alterations.

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.

Influência do uso continuado de fluoxetina nas dosagens séricas de prolactina em mulheres / Influence of the continous use of fluoxetin in the measurement of serum prolactin in women

A importância da dosagem de prolactina reside principalmente no fato de sua utilização diagnóstica em alterações da hipófise anterior. Alguns medicamentos, como a fluoxetina, podem alterar a secreção da prolactina. Assim, o foco deste trabalho foi ode avaliar a real importância de se considerar o uso da fluoxetina, um inibidor seletivo da recaptação da serotonina (ISRS), como um interferente na interpretação dos valores de dosagens laboratoriais da prolactina em mulheres. Foram analisados dados de 95 mulheres, com idade entre 15 e 70 anos, que realizaram dosagens séricas de prolactina. As mulheres em tratamento com a fluoxetina apresentaram um aumento significativo de prolactina. Este aumento foi maior em mulheres com até 29 anos, onde chegou a níveis considerados patológicos, diminuindo de uma maneira inversamente proporcional com o aumento da faixa etária. Acima dos 45 anos, onde a maioria das mulheres encontra-se na menopausa, os valores de prolactina não se alteram com o uso da fluoxetina.

Avaliação da pressão inspiratória em crianças com aumento do volume de tonsilas / Evaluation of inspiratory pressure in children with enlarged tonsils and adenoids

Crianças com aumento do volume de tonsilas palatina e faríngea freqüentemente apresentam anormalidades respiratórias tais como ronco, respiração oral e apnéia do sono. Sabe-se que a obstrução de vias aéreas superiores e conseqüentemente a respiração oral podem resultar em problemas pulmonares. OBJETIVO: Avaliar a pressão inspiratória em crianças com obstrução de vias aéreas superiores devido ao aumento do volume de tonsilas. FORMA DE ESTUDO: clínico com coorte transversal. MATERIAL E MÉTODO: Nós avaliamos 37 crianças (4-13 anos, ambos os sexos) com aumento do volume de tonsilas que seriam submetidas à cirurgia de Adenoamigdalectomia na Divisão de Otorrinolaringologia da Universidade de São Paulo no mesmo período. O grupo controle foi composto de 28 crianças sem aumento de volume tonsilar que foram submetidas aos mesmos testes. A pressão Inspiratória foi obtida pelo uso do manovacuômetro. RESULTADOS: Observamos uma menor pressão inspiratória no grupo com aumento do volume de tonsilas. A média do grupo com aumento do volume das tonsilas foi 14,607 cm/H2O e do grupo normal foi de 27,580 cm/H2O (P< 0,001). CONCLUSÃO: O aumento de volume de tonsilas palatina e faríngea foi associado a uma menor pressão inspiratória, resultando em um aumento do esforço respiratório e do trabalho dos músculos envolvidos.

Marcadores laboratoriais do choque séptico / Laboratory markers of the septic shock

O deste trabalho foi fazer uma revisão sobre os principais marcadores laboratoriais de suporte para o diagnóstico do choque séptico. Foram pesquisados livros e artigos científicos, com enfoque nos assuntos abordados, publicados no período de 1989-2005. Os marcadores laboratoriais são úteis na avaliação do choque séptico, auxiliando no diagnóstico e na detecção precoce de disfunções orgânicas. No sangue e na urina destes pacientes se refletem as alterações biofísico-químicas que se operam nos tecidos, na vigência da deficiência circulatória dos chocados. A análise laboratorial pode revelar a maioria das alterações fisiopatológicas.

O antígeno prostático específico e sua importância na decisão clínica no câncer de próstata / The prostatic specific antigen and its importance in the clinical decision in the prostate cancer

O câncer de próstata (CaP) representa um problema de saúde pública de proporções cada vez mais importantes. É uma das neoplasias mais frequentes nos homens e representa uma das principais causas de morte na população. A busca de métodos diagnósticos para as neoplasias é um constante objetivo clínico laboratorial. Exame físico, métodos de imagem e dosagens laboratoriais compreendem o conjunto de auxílio diagnóstico no CaP. O antígeno prostático específico (PSA) é produzido pelo tecido prostático normal, bem como, em casos de Hiperplasia Prostática Benigna (HPB) e no CaP. Sua dosagem constitui importante método laboratorial na prática médica, uma vez que se apresenta com grande valor no rastreamento, diagnóstico e acompanhamento dos casos de CaP. O entendimento do seu papel pelo farmacêutico-bioquímico, bem como, a interação com a equipe clínica mostra-se promissor para influenciar as decisões diagnóstico-terapêuticas.

Prostate cancer represents a public health concern whose proportions are becoming increasingly important. It is one of the most common neoplasia among men and it represents one of the main causes of death in the population. The search for diagnostic methods for this neoplasia has been a constant laboratory clinic target. Physical checking, imaging methods and laboratory dosages compose the range of diagnostic support when dealing with prostate cancer...

Efeito da frutose-1, 6bisfosfato sobre os níveis séricos e urinários de lactato em ratos com sepse experimental / Effect of fructose-1, 6-bisphosphate on serum and urine levels of lactate in rats with experimental sepsis

As alterções celulares e sistêmicas durante a sepse ocasionam distúrbios na circulação, queda na perfuração tecidual e consequentemente déficit de energia celular. A frutose-1-6-bisfosfato (FBP) tem demonstrado efeitos protetores em diversas situações patológicas, inclusive sepse. O objetivo deste travalho foi verificar a concentração de FBP em animais com sepse experimental. Estudo controlado em ratos Wistar divididos em 4 grupos: grupo controle com FBP(500 mg/kg). A concentração sérica de lactato aumentou signitivamente no grupo séptico. Analisando a depuração de creatinina endógena(DCE) verificou-se, que somente o grupo séptico apresentou uma diminuição significativa. Já o lactato urinário não demonstrou alterações entre os grupos de controle, séptico e séptico tratado, aumentando, porém significativamente no grupo co FBP. Este estudo demonstrou que o lactato urinário é bom marcador de perfusão tecidual na spse. Também pôde-se verificar que a ação protetora da FBP não é por melhora da perfusão tecidual, mas provavelmente por outros efeitos já descritos, tais como, ação antiflamatória, manutenção dos níveis de energia da célula, estabilização da membrana celular.