Low-intensity pulsed ultrasound (LIPUS) stimulates mineralization of MC3T3-E1 cells through calcium and phosphate uptake.

The present study aimed to evaluate the effect of low-intensity pulsed ultrasound (LIPUS) on pre-osteoblast mineralization using in vitro bioassays. Pre-osteoblastic MC3T3-E1 cells were exposed to LIPUS at 1 MHz frequency, 0.2 W/cm2 intensity and 20% duty cycle for 30 min. The analyses were carried out up to 336 h (14 days) after exposure. The concentration of collagen, phosphate, alkaline phosphatase, calcium and transforming growth factor beta 1 (TGF-ß1) in cell supernatant and the presence of calcium deposits in the cells were analyzed. Our results showed that LIPUS promotes mineralized nodules formation. Collagen, phosphate, and calcium levels were decreased in cell supernatant at 192 h after LIPUS exposure. However, alkaline phosphatase and TGF-ß1 concentrations remained unchanged. Therapeutic pulsed ultrasound is capable of stimulating differentiation and mineralization of pre-osteoblastic MC3T3-E1 cells by calcium and phosphate uptake with consequent hydroxyapatite formation.

Safety and patient subjective efficacy of using galvanopuncture for the treatment of striae distensae.

BACKGROUND: Striae distensae are linear atrophic dermal scars with associated epidermal atrophy. This recurrent skin disorder causes a significant cosmetic and psychologic concern and remains a therapeutic challenge, especially when they are mature and hypopigmented (striae alba). AIMS: In this prospective single-center study, we evaluated the efficacy, safety, and patient's satisfaction of galvanopuncture for the treatment of striae alba. PATIENTS/METHODS: Thirty-two female subjects with striae alba present on the buttocks were treated with galvanopuncture once a week over a period of 10 weeks. Photographs and a percentage category scale were used to assess striae improvement and patient's satisfaction. Biochemical analyses were performed to assess possible systemic inflammatory effects or oxidative stress induction by the treatment. RESULTS: All patients achieved a substantial increase in clinical improvement in their striae within 10 treatment sessions. Galvanopuncture did not induce any inflammatory effect; however, it reduced oxidative injury. CONCLUSION: The use of galvanopuncture for the treatment of striae alba demonstrated a significant improvement in the lesions with visible results. This study supports the high degree of patient's satisfaction and demonstrate the safe and effective use of galvanopuncture in the treatment of striae alba on several skin types.

Use of ischemia modified albumin for the diagnosis of myocardial infarction / Uso da albumina modificada isquêmica no diagnóstico de infarto do miocárdio

ABSTRACT Introduction: Literature reports addressing ischemia modified albumin (IMA) as a good marker for the early diagnosis of myocardial ischemia through albumin cobalt binding (ACB) test, that is before myocardial infarction (MI) occurs. Objective: To evaluate the IMA plasmatic levels in infarcted patients, in order to verify its potential as an early marker for early diagnosis of MI, investigate its correlation with existing cardiac biomarkers such as total creatine kinase (CK) and creatine kinase-MB fraction (CK-MB), as well as to assess the correlation between IMA and oxidative stress. Methods: The sample was divided into two groups according to serum troponin I (TnI) results; one group of infarcted patients (with MI) (TnI levels higher than 0.05 ng/ml), and the other group of non-infarcted patients (without MI) (TnI levels lower than 0.05 ng/ml). The results of total CK, CK-MB, thiobarbituric acid reactive substances (TBARS), and IMA were analyzed in both groups. Results: Regarding the existing cardiac markers, there was a significant increase of total CK and CK-MB levels in With MI group. In relation to the oxidative stress parameter, a significant increase was observed in with MI group compared to without MI group. However, IMA showed no significant difference between the groups; and also there was no significant correlation between IMA and the cardiac markers. There was no correlation between IMA and TBARS. Conclusion: Our results suggest that IMA cannot be used alone for the diagnosis of MI.

RESUMO Introdução: Relatos na literatura abordam a albumina modificada isquêmica (AMI) como um bom marcador precoce para o diagnóstico de isquemia miocárdica por meio do albumin cobalt binding (ACB) test, ou seja, antes do infarto do miocárdico (IM). Objetivo: Avaliar os níveis plasmáticos de AMI em pacientes infartados a fim de verificar o seu potencial como marcador precoce para o diagnóstico antecipado do IM, investigar sua correlação com os biomarcadores cardíacos já existentes, como creatinaquinase (CK) total e creatinaquinase fração MB (CK-MB), além de avaliar a correlação de AMI com o estresse oxidativo. Métodos: Foram separados dois grupos de acordo com resultados séricos da troponina I (TnI), um com pacientes infartados (TnI superior a 0,05 ng/ml) e outro com pacientes não infartados (TnI inferior a 0,05 ng/ml). Foram analisados os resultados de CK total, CK-MB, substâncias reativas ao ácido tiobarbitúrico (TBARS) e AMI em ambos os grupos. Resultados: Em relação aos marcadores cardíacos existentes, houve aumento significativo de CK total e CK-MB no grupo dos infartados; já em relação ao parâmetro de estresse oxidativo, foi observado aumento significativo no grupo dos infartados quando comparado com o dos não infartados. Contudo, a AMI não apresentou diferença significativa entre os grupos; também não houve correlação relevante entre AMI e os marcadores cardíacos, bem como não foi observada correlação de AMI com TBARS. Conclusão: Nossos resultados sugerem que AMI não pode ser utilizada isoladamente como diagnóstico de IM.

Therapeutic ultrasound stimulates MC3T3-E1 cell proliferation through the activation of NF-κB1, p38α, and mTOR.

BACKGROUND AND OBJECTIVES: As the population ages, osteometabolic diseases and osteoporotic fractures emerge, resulting in substantial healthcare resource utilization and impaired quality of life. Many types of mechanical stimulation have the potential of being recognized by bone cells after a mechanical sign is transformed into a biological one (a process called mechanotransduction). The therapeutic ultrasound (TU) is one of several resources capable of promoting bone cell mechanical stimulation. Therefore, the main purpose of present study was to evaluate the effect of TU on the proliferation of pre-osteoblasts using in vitro bioassays. STUDY DESIGN/MATERIALS AND METHODS: We used MC3T3-E1 pre-osteoblast lineage cells kept in Alpha medium. Cells were treated using pulsed mode therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA), duty cycle of 20%, for 30 minutes. Nifedipine and rapamycin were used to further investigate the role of L-type Ca(2+) channels and mTOR pathway. Intracellular calcium, TGF-ß1, magnesium, and the mRNA levels of osteopontin, osteonectin, NF-κB1, p38α were evaluated. RESULTS: The results show that TU stimulates the growth of MC3T3-E1 cells and decreases the supernatant calcium and magnesium content. Also, it increases intracellular calcium, activates NF-κB1 and mTOR complex via p38α. Moreover, TU promoted a decrease in the TGF-ß1 synthesis, which is a cell growth inhibitor. CONCLUSIONS: Therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA) and pulsed mode, for 30 minutes, was able to increase the proliferation of preosteoblast-like bone cells. This effect was mediated by a calcium influx, with a consequent activation of the mTOR pathway, through increased NF-κB1 and p38α.

Effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life.

The present study aimed to evaluate the long-term effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As adults, fear/anxiety behavior was evaluated in the elevated plus maze. The following week, saline solution or LPS was administered and, after 12h, serum (inflammatory cytokines), liver (mitochondrial complexes and oxidative stress) and adrenal gland samples (angiotensin II type 1 and 2 receptors) were collected. There was an increase in the fear/anxiety behavior in the nLPS group. Neonatal administration of LPS increased the mRNA expression of the AT1 receptor and decreased the mRNA expression of the AT2 receptor in the adrenal glands of males. The complexes II and II-III increased in the nLPS saline male group when compared to control. The LPS administration in adult females, regardless of the neonatal treatment, induced a decrease of the glutathione enzyme activity. There were no differences in the inflammatory cytokines. The results showed that neonatal inflammation influenced mitochondrial respiratory chain metabolism and angiotensin II receptors in a sex-dependent manner. Balb/c mice fear and anxiety behaviors in adulthood were programmed by early life inflammatory stress.

Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil.

Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.

Serological profile of candidates for corneal donation / Perfil sorológico de candidatos a doação de córneas

Objetive: The purpose of this study is to map the serological profile of candidates to corneal donation at Irmandade Santa Casa de Misericórdia de Porto Alegre, identifying the percentage of disposal by serology and the marker involved. Methods: There have been analised – retrospectively – the results of serology of all corneal donors, made between the period of 1st january 2006 and 31st december 2012. Data analised were related to age, gender and the results of serology pertinent to viral markers (HBsAg, anti-HBc, anti-HCV and anti-HIV), these, determined by immunosorbent tests (ELISA). Results: In the period of the study, there were 2476 corneal donors at the institution, with a major incidence on the male gender, on an average of 58.7 years old. 23% of retention because of serological unfitness was also identified, that is, 570 samples were non-negative to any of the used tests. The marker anti- HBc was the most prevalent on the studied population, followed by the Hepatitis C virus (HCV) and by the Human Immunodeficiency Virus (HIV). Conclusion: From the data found through this study, it is essential to have the participation of an efficient service on the serological evaluation of the candidates to corneal donation, once the security of the receptor must be taken into consideration in a population of donors with 23% of unfitness prevalence, in which the most prevalent marker is the one of Hepatits B. .

Objetivo: O intento deste desígnio é mapear o perfil sorológico dos candidatos a doação de córneas na Irmandade Santa Casa de Misericórdia de Porto Alegre, identificando o percentual de descarte por sorologia e o marcador envolvido. Métodos: Foram analisados – retrospectivamente – os resultados da sorologia de todos os doadores de córneas compreendidos entre 01 de janeiro de 2006 a 31 de dezembro de 2012. Foram avaliados os dados de idade, sexo e os resultados da sorologia pertinentes aos marcadores virais (HBsAg, anti-HBc, anti-HCV e anti-HIV) determinados por testes imunoenzimáticos (ELISA). Resultados: No período coberto pelo estudo, houve 2476 doadores de córneas na instituição, com maior ocorrência do sexo masculino e média de 58,7 anos de idade. Foram verificados 23,0% de retenção por inaptidão sorológica, ou seja, 570 amostras mostraram-se não-negativas para qualquer dos testes empregados. O marcador anti-HBc foi o mais prevalente na população aferida, seguido pelo vírus da hepatite C (HCV) e pelo vírus da imunodeficiência humana (HIV). Conclusão: Diante dos dados encontrados por este estudo, torna-se decisiva a participação de um serviço eficaz no tangente à avaliação sorológica dos candidatos à doação de córnea, uma vez que a segurança do receptor deve ser considerada numa população de doadores com prevalência de retenção por inaptidão sorológica de 23,0%, donde o marcador mais prevalente é o de hepatite B. .

Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model.

OBJECTIVE AND DESIGN: Mesenchymal stem cells (MSCs) are potent modulators of immune responses. Sepsis is the association of a systemic inflammatory response with an infection. The aim of this study was to test the ability of MSCs derived from adipose tissue, which have immunomodulatory effects, and to inhibit the septic process in an experimental model of mice. METHODS: Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10(6) cells/animal). RESULTS: In the control group, there were no deaths; in the untreated septic group, the mortality rate was 100 % within 26 h; in the septic group treated with MSCs, the mortality rate reached 40 % within 26 h. The group treated with MSCs was able to reduce the markers of tissue damage in the liver and pancreas. The treated group had a reduction of inflammatory markers. Furthermore, the MSCs-treated group was able to inhibit the increase of apoptosis in splenocytes observed in the untreated septic group. CONCLUSIONS: Our data showed that MSCs ameliorated the immune response with decrease of inflammatory cytokines and increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and, consequently, inhibited tissue damage during sepsis.

Perfil lipídico de transplantados renais em uso de terapia imunossupressora / Lipid profile in post renal transplant patients treated with immunosuppressive therapy

Objetivo: A prevalência de alterações no perfil lipídico dos transplantados renais é muito alta, sendo a doença cardiovascular uma das principais causas de mortalidade nesses pacientes. Mesmo após o transplante renal, as complicações cardíacas não diminuem. O objetivo foi avaliar o perfil lipídico de pacientes transplantados renais em uso de terapia imunossupressora e relacionar qual dos imunossupressores estaria associado a alterações no perfil lipídico. Métodos: Estudo retrospectivo realizado com 186 pacientes em terapia imunossupressora pós-transplante renal com ciclosporina, tacrolimus ou sirolimus. Foram coletadas amostras dos pacientes que realizaram transplante renal entre 2002 e 2007 , na Irmandade Santa Casa de Misericórdia de Porto Alegre, e que foram incluídos na pesquisa. Resultados: Foi observado que os níveis de colesterol aumentaram nos pacientes em uso de ciclosporina e sirolimus. O HDL-C mostrou-se mais elevado em todos os grupos, independente do tempo, após o transplante renal. Quanto ao LDL-C, verificou-se diminuição com o passar do tempo de tratamento no grupo que fazia uso de ciclosporina. A razão colesterol total/HDL-C diminuiu com o tratamento de ciclosporina e de tacrolimus após 24 meses. Conclusão: Os resultados sugerem que o tacrolimus e a ciclosporina são os imunossupressores menos prejudiciais ao perfil lipídico dos pacientes transplantados renais, no entanto, o sirolimus está associado à maior alteração no perfil lipídico, podendo levar os pacientes a um pior prognóstico cardíaco.

Nephroprotective and anti-inflammatory effects of aqueous extract of Melissa officinalis L. on acetaminophen-induced and pleurisy-induced lesions in rats

This study assessed the bioactive properties of an aqueous extract of M. officinalis for its anti-inflammatory activity and its protection against hepatic and renal lesions induced by acetaminophen (APAP). Animals pre-treated with the crude extract in pleurisy induced by carrageenan showed a reduction in the amounts of exudate, in the numbers of leukocytes and polymorphonuclear cells. Intragastric administration of the extract for seven days prior to the APAP-induced lesion showed no protective effect on the liver. The treatment with the extract induced an increase of serum aspartate aminotransferase, indicating a rise of toxicity. Contrarily, the same treatment reduced the APAP induced lesion in kidney, with respect to ν-glutamyltransferase. The results suggested that the extract was not hepatoprotective and could lead to an increase in the lesions induced by the APAP. On the other hand, the extract was nephroprotective against the lesions induced by the APAP and showed an anti-inflammatory effect on pleurisy carrageenan-induced.

N-acetilcisteína e frutose-1, 6-bisfosfato: efeito imunomodulador em cultura de células mononucleares / N-acetilcisteína e frutose-1,6-bisfosfato: efeito imunomodulador em cultura de células mononucleares

INTRODUCTION: Sepsis is a complex syndrome caused by an uncontrolled systemic inflammatory response. Inflammatory cytokines play a pivotal role in septic shock pathogenesis. Therapeutic strategies have been tested in order to modulate the excessive generation or function of sepsis mediators. OBJECTIVE: The objective of the present study was to investigate the therapeutic effect of N-acetylcysteine (NAC) and its association with fructose-1,6-bisphosphate (FBP) on T-lymphocytes proliferation, interleukin-1β (IL-1β) and monocyte chemotactic protein-1 (MCP-1) levels. MATERIAL AND METHODS: Peripheral blood mononuclear cell samples were isolated from healthy individuals. T-lymphocytes were stimulated with phytohemagglutinin for 96 hours and submitted to different concentrations of NAC or NAC associated with FBP. RESULTS: NAC (10 and 15 mM) and NAC (15 mM) associated with FBP reduced T-lymphocytes proliferation. IL-1β levels rose in the presence of both NAC (15 mM) and NAC with FBP (1.25 mM). MCP-1 levels were reduced only by NAC (15 mM) associated with FBP (1.25 mM). CONCLUSION: The results suggest that both NAC itself and NAC associated with FBP inhibit cellular proliferation, acting as potent immunomodulatory agents, which corroborates its use in the treatment of inflammatory diseases.

INTRODUÇÃO: A sepse é uma síndrome complexa causada pela resposta inflamatória sistêmica descontrolada. As citocinas inflamatórias representam papel central na patogênese do choque séptico. Têm sido testadas estratégias terapêuticas a fim de modular a geração ou a função excessiva de mediadores na sepse. OBJETIVO: O objetivo deste estudo foi investigar o efeito terapêutico da N-acetilcisteína (NAC) e sua associação com a frutose-1,6-bisfosfato (FBP) sobre a proliferação de linfócitos T e a geração de interleucina-1β (IL-1β) e proteína quimiotática de monócitos 1 (MCP-1) em cultura celular. MATERIAL E MÉTODOS: Foram isoladas células mononucleares de sangue periférico de indivíduos saudáveis. Os linfócitos T foram estimulados por 96 horas com fitohemaglutinina e submetidos a diferentes concentrações de NAC ou NAC associada à FBP (1,25 mM). RESULTADOS: O tratamento com NAC (10 e 15 mM) ou NAC (15 mM) associado à FBP reduziu a proliferação celular. Os níveis de IL-1β aumentaram com a presença de NAC (15 mM) e NAC + FBP. A concentração de MCP-1 mostrou-se reduzida apenas no grupo tratado com NAC associada à FBP. CONCLUSÃO: Os resultados sugerem que tanto a NAC quanto a NAC associada à FBP são capazes de inibir a proliferação celular, atuando como potentes agentes imunomoduladores, sugerindo seu uso em doenças inflamatórias.

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.

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.

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.

Effect of N-acetylcysteine and fructose-1,6-bisphosphate in the treatment of experimental sepsis.

Sepsis is a syndrome caused by uncontrolled systemic inflammatory response of the individual, which represents a serious epidemiological problem worldwide. The aim of this study was to investigate the effect of N-acetylcysteine (NAC) and fructose-1,6-bisphosphate (FBP) in the treatment of experimental sepsis. We used rats that were divided into five experimental groups: normal control (not induced), septic control (induced using a capsule with non sterile fecal content and Escherichia coli), treated with FBP (500 mg/kg i.p.), treated with NAC (150 mg/kg i.p.), and treated with the combination of FBP with NAC. In the group treated with NAC, 16.68% of the mice survived, the FBP reduced the mortality of mice during the acute stage of the disease and increased the animals' survival time in 33.34%, and the combination of drugs had no effect. Our results show that NAC prevented the mortality of animals after septic induction. These data confirm the validity of the use of NAC in the treatment of sepsis. Our data also show that the synergistic action with FBP does not improve the picture.

Anti-inflammatory and immunomodulatory effects of RDV-8 [C18H22N2O2S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] in a rat model of induced pleurisy and in vitro lymphoproliferation.

RDV-8 [C(18)H(22)N(2)O(2)S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] is derived from the 4-thioxopyrimidine, and presents important clinical effects. The present study explored the RDV-8 effects in the proliferation of human peripheral blood mononuclear cells (PBMCs), as well as in a pleurisy-induced rat model. PBMCs were directly plated in four different RDV-8 concentrations (0.0125, 0.025, 0.05 and 0.1 mg/mL). RDV-8 decreased cell proliferation and monocyte chemotactic protein 1 synthesis. The interleukin 1 levels and the cytotoxic effect were not significantly affected by RDV-8 treatment. In the carrageenan-induced pleurisy model, the RDV-8 (3 mg/kg) treatment induced a significant reduction in the exudate volume, in the polymorphonuclear leukocyte migration and in the pleural exudate NO levels. The results indicate that RDV-8 may have an immunomodulatory effect, as well as anti-inflammatory actions suggesting that it could represent a new strategy in the inflammatory response modulation.

Effect of fructose-1,6-bisphosphate on the nephrotoxicity induced by cisplatin in rats.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is frequently limited by nephrotoxicity. The study presented here attempted to evaluate the effect of fructose-1,6-bisphosphate in the cisplatin-induced nephrotoxicity in rats. The drugs were administered intraperitoneally as a single dose: sodium chloride 0.9%, cisplatin (6 mg/kg), fructose-1,6-bisphosphate (500 mg/kg), and cisplatin plus fructose-1,6-bisphosphate (6 and 500 mg/kg, respectively). The use of cisplatin resulted in significant elevation of serum creatinine and urea. The group that received cisplatin plus fructose-1,6-bisphosphate presented a significantly lower level of creatinine and urea compared to the cisplatin group. Acute tubular necrosis was demonstrated in the animals that received cisplatin and a less severe one in the cisplatin plus fructose-1,6-bisphosphate group. Fructose-1,6-bisphosphate has a protective effect over renal function and renal parenchyma in a rat experimental model of cisplatin-induced nephrotoxicity. The anti-inflammatory effect of fructose-1,6-bisphosphate confirms its protective effect in cases of cellular injury.

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.

Anti-inflammatory and immunomodulatory effects of Baccharis trimera aqueous extract on induced pleurisy in rats and lymphoproliferation in vitro.

Baccharis trimera is a widespread South American plant known as "carqueja". Medicinal teas prepared from the aerial parts of this plant are used in folk medicine in cases of liver diseases and inflammatory processes. We evaluated the effects of aqueous extract of B. trimera in the experimental inflammatory model of carrageenan-induced pleurisy in rat. The injection of carrageenan into the pleural cavity induces an influx of cells and fluid accumulation with a large number of polymorphonuclear leukocytes and increase of protein levels. The inflammation parameters were attenuated when B. trimera (400 and 800 mg/kg, i.p.) was administrated 30 min before the carrageenan. The immunomodulatory effects were evaluated in vitro on human peripheral blood mononuclear cells. The extract in concentration of 25, 50 and 100 mg/mL presented inhibited the T-lymphocytes proliferation stimulated by phytohemagglutinin, but these extract concentrations also presented cytotoxic effect. These results showed that the aqueous extract of B. trimera has anti-inflammatory effect.

A high-performance liquid chromatography method for the determination of carbamazepine and carbamazepine-10,11-epoxide and its comparison with chemiluminescent immunoassay.

BACKGROUND: Carbamazepine is a first-choice antiepileptic drug for the treatment of simple and complex partial seizures. The use of an established therapeutic range for carbamazepine concentration is limited by the presence of carbamazepine-10,11-epoxide, its active metabolite that significantly contributes to the efficacy and toxicity and is not routinely measured and accounted for. This article describes the development of a HPLC method for determination of carbamazepine and carbamazepine-10,11-epoxide in serum, and compares it with chemiluminescence immunoassay to evaluate the importance of considering the active metabolite in therapeutic strategies. METHODS: The procedure involves protein precipitation, separation on a reverse-phase column and ultraviolet detection. The analytical procedure proved to be sensitive, selective, precise, accurate and linear (regression coefficients >0.999) in the range of 0.5-25.0 microg/mL and 0.1-10.0 microg/mL for quantification of carbamazepine and carbamazepine-10,11-epoxide, respectively. For the comparison between methods, serum samples of 75 patients using the medication were evaluated. RESULTS: The Pearson correlation coefficient showed that the carbamazepine concentrations measured by HPLC are significantly higher than those obtained by immunoassay (mean difference of 1.07 microg/mL, 95% limits of agreement from -0.65 to 2.80 microg/mL). CONCLUSIONS: This difference may be decisive for the therapy. In some cases, this may affect the individual dosage adjustment and subsequent treatment.