Anti-oxidative and anti-ulcerogenic activity of Ipomoea imperati

Ipomoea imperati (Vahl) Griseb., Convolvulaceae, is used in traditional medicine for the treatment of inflammation, swelling and wounds, as well as to treat pains and stomach problems. This work evaluates the anti-oxidative activity by ESR (Electron Spin Resonance spectroscopy) and the preventive and curative actions of I. imperati in gastric ulcer animal model. Ipomoea imperati (200 mg/kg, p.o.) prevented the formation of gastric lesions in 78% (p<0.05) when compared with the negative control tween 80. Lanzoprazole, prevented in 85% the gastric lesions formation induced by ethanol (p<0.05). Therefore, the oral administration of I. imperati one hour before the ulcerogenic agent prevented the ulcer formation, conserving the citoprotection characteristics of the gastric mucosa and assuring the integrity of gastric glands and gastric fossets. The healing activity of I. imperati (200 mg/kg, p.o.) evaluated in chronic ulcer experiments induced by the acetic acid, was 72% (p<0.05). The positive control, ranitidine, healed 78% of the gastric lesions (p<0.05). The histological analysis confirmed the recovery of the mucosal layer and the muscle mucosal layer harmed by the acetic acid. Experiments in vitro with DPPH (2.2-diphenyl-1-picrylhydrazyl) of anti-oxidative activity demonstrated that I. imperati presents an IC50 of 0.73±0.01 mg/mL.

Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (μm) and by relative fibrosis area (RFA, %). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU). RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established end-organ damage is reached.

Avaliação citométrica dos adipócitos localizados no tecido subcutâneo da parede anterior do abdome após infiltração percutânea de CO2

OBJETIVO: Avaliar os efeitos da infiltração de dióxido de carbono em adipócitos presentes na parede abdominal. MÉTODOS: Quinze voluntárias foram submetidas a sessões de infusão de CO2 durante três semanas consecutivas (duas sessões por semana com intervalos de dois a três dias entre cada sessão). O volume de gás carbônico infundido por sessão, em pontos previamente demarcados, foi sempre calculado com base na superfície da área a ser tratada, com volume infundido fixo de 250 mL/100cm² de superfície tratada. Os pontos de infiltração foram demarcados respeitando-se o limite eqüidistante 2cm entre eles. Em cada ponto se injetou 10mL, por sessão, com fluxo de 80mL/min. Foram colhidos fragmentos de tecido celular subcutâneo da parede abdominal anterior antes e após o tratamento. O número e as alterações histomorfológicas dos adipócitos (diâmetro médio, perímetro, comprimento, largura e número de adipócitos por campos de observação) foram mensurados por citometria computadorizada. Os resultados foram analisados com o teste t de Student pareado, adotando-se nível de significância de 5% (p<0,05). RESULTADOS: Encontrou-se redução significativa no número de adipócitos da parede abdominal e na área, diâmetro, perímetro, comprimento e largura após o uso da hipercapnia (p=0,0001). CONCLUSÃO: A infiltração percutânea de CO2 reduz a população e modifica a morfologia dos adipócitos presentes na parede abdominal anterior.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7%) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years) were either overweight (4) or obese (3); 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

Monitorização materno-fetal durante procedimento odontológico em portadora de cardiopatia valvar

FUNDAMENTO: Os efeitos da anestesia local em odontologia com lidocaína e epinefrina, sobre parâmetros cardiovasculares de gestantes portadoras de valvopatias e seus conceptos, não estão esclarecidos. OBJETIVO: Avaliar e analisar parâmetros da cardiotocografia, de pressão arterial e eletrocardiográficos da gestante portadora de doença valvar reumática, quando submetida à anestesia local com 1,8 ml de lidocaína 2% sem vasoconstritor e com epinefrina 1:100.000, durante procedimento odontológico restaurador. MÉTODOS: Realizamos monitorização ambulatorial da pressão arterial, eletrocardiografia ambulatorial materna e cardiotocografia de 31 portadoras de cardiopatia reumática, entre a 28ª e 37ª semana de gestação, divididas em dois grupos conforme presença ou não do vasoconstritor RESULTADOS: Demonstrou-se redução significativa dos valores de frequência cardíaca materna nos dois grupos, durante o procedimento, quando comparado aos demais períodos (p < 0,001). Houve ocorrência de arritmia cardíaca em 9 (29,0%) pacientes, das quais 7 (41,8%) pertencentes ao grupo de 17 gestantes que recebeu anestesia com adrenalina. A pressão arterial materna não apresentou diferença quando comparamos períodos ou grupos (p > 0,05). O mesmo ocorreu (p > 0,05) com número de contrações uterinas, nível e variabilidade da linha de base e número de acelerações da frequência cardíaca fetal. CONCLUSÃO: O uso de 1,8 ml de lidocaína 2% associado à adrenalina mostrou-se seguro e eficaz em procedimento odontológico restaurador durante a gestação de mulheres com cardiopatia valvar reumática.

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats

PURPOSE: To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS: Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS: In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0±2.9 mmHg and 111.0±6.7 mmHg, respectively) within 60 minutes. TNF-α levels in BAL do not differ significantly in the HCl+P group (516.0±5.9 pg/mL), and the HCl+S (513.0±10.6 pg/mL). CONCLUSION: The use of prone position improved oxygenation, but did not reduce TNF-α in BAL upon lung dysfunction induced by HCl.

A fototerapia com diodo emissor de luz (LEDT) aplicada pré-exercício inibe a peroxidação lipídica em atletas após exercício de alta intensidade: um estudo preliminar

Estresse oxidativo é o termo geralmente utilizado para descrever os danos causados pelo desequilíbrio entre pró-oxidantes e antioxidantes no organismo. O aumento no consumo de O2 induzido pelo exercício físico está associado ao aumento das espécies reativas de oxigênio (EROs) sendo estas indutoras do estresse oxidativo. Embora as evidências indiquem um provável efeito inibitório da fototerapia com diodos emissores de luz (LEDT) sobre a produção das EROs, não existem estudos observando tal efeito em atletas. Este estudo preliminar destina-se a verificar os efeitos da aplicação de LEDT previamente ao exercício de alta intensidade sobre a peroxidação lipídica, mensurada através dos níveis sanguíneos de substâncias reativas ao ácido tiobarbitúrico (TBARS). Todos os seis atletas de voleibol do sexo masculino foram submetidos às duas situações: aplicação de LEDT efetiva e aplicação de LEDT placebo. O desempenho no protocolo de exercício adotado não revelou diferença (p > 0,05) entre as duas situações nas variáveis potência pico, potência média e índice de fadiga. Os resultados relacionados com a peroxidação lipídica foram: na situação LEDT efetiva, não foi possível observar diferença estatisticamente significante (p > 0,05) entre os níveis pré e pós-exercício (6,98 ± 0,81 e 7,02 ± 0,47nmol/mL); na situação LEDT (LBP) placebo, houve diferença estatisticamente significante (p = 0,05) entre os valores pré e pós-exercício (7,09 ± 1,28 e 8,43 ± 0,71nmol/mL). Tais resultados demonstram que a aplicação efetiva de LEDT parece ser eficaz no controle da peroxidação lipídica em atletas submetidos a exercício intenso

Exposição repetida à cafeína aumenta a atividade locomotora induzida pelo femproporex em ratos adolescentes e adultos

A cafeína e o femproporex são substâncias psicoestimulantes. O femproporex é muito utilizado no Brasil como anorexígeno enquanto a cafeína é amplamente consumida como constituinte regular da dieta. A administração repetida de psicoestimulantes induz sensibilização comportamental que se caracteriza pelo aumento progressivo dos seus efeitos locomotores. Pode ocorrer ainda sensibilização cruzada entre essas substâncias. Investigamos se a administração repetida de cafeína aumenta a locomoção induzida pelo femproporex em ratos adolescentes e adultos. Quarenta e oito ratos adolescentes (dia pós-natal 27) e 32 adultos (dia pós-natal 60) foram distribuídos em dois grupos que receberam injeção intra-peritoneal de 10,0 mg/kg de cafeína (CAF) (adolescentes N = 24; adultos N = 16) ou salina (SAL) (adolescentes N = 24; adultos N = 16) diariamente durante 10 dias. Três dias após a última injeção, cada grupo CAF ou SAL foi subdividido em dois subgrupos que receberam injeção i.p. de salina (SAL) (1 mL/kg) ou femproporex (FEM) (2,0 mg/kg). Após as injeções, a atividade locomotora foi avaliada automaticamente em intervalos de 5 minutos durante 1 hora. Nossos resultados demonstraram que em ratos adolescentes e adultos o pré-tratamento com CAF aumenta a atividade locomotora induzida pela administração aguda de FEM, sugerindo que a cafeína causa sensibilização aos efeitos locomotores desse derivado anfetamínico.

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats

This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7%), WSS (Wistar/E+: 36; SHR/E+: 40%) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

Antiplatelet activity of Croton celditifolius

Croton celtidifolius Baill is a tree found in the Atlantic Forest South of Brazil, mainly in Santa Catarina. The bark and leaf infusions of this medicinal plant have been popularly used for the treatment of inflammatory diseases. The anti-aggregant activity of C. celtidifolius crude extract (CE) and the column chromatography (CC) isolated compounds flavonoids, catechin and gallocatechin were evaluated in human blood platelets. The platelet-rich plasma (PRP) was incubated with different concentrations of flavonóides (50 - 200 µg/mL) to be tested before platelet aggregation was induced by the agonists adenosine 5'diphosphate (ADP) and collagen. At 200 µg/mL the CE, catechin and gallocatechin markedly inhibited platelet aggregation with the aggregant agents. Using ATP production as an index of platelet secretory capacity, we observed a decreased production of ATP in platelets treated with flavonoids when stimulated by collagen. On the other hand, the flavonoids did not promote inhibitory effect on prothrombin time (PT), thromboplastin time (APTT) and thrombin time (TT). In conclusion, these observations suggest that C. celtidifolius is likely to exert an inhibitory action on platelets in vitro by suppressing secretion and platelet aggregation.

Photodynamic inactivation of four Candida species induced by photogem®

This study evaluated the in vitro susceptibility of C. albicans, C. dubliniensis, C. tropicalis and C. krusei to photodynamic therapy (PDT) induced by Photogem® and light emitting diode (LED). Suspensions of each Candida strain were treated with three photosensitizer (PS) concentrations (10, 25 and 50 mg/L) and exposed to 18.0, 25.5 and 37.5 J/cm² LED light fluences (λ ~ 455 nm). Control suspensions were treated only with PS concentrations, only exposed to the LED light fluences or not exposed to LED light or PS. Sixteen experimental conditions were obtained and each condition was repeated three times. From each sample, serial dilutions were obtained and aliquots were plated on Sabouraud Dextrose Agar. After incubation of plates (37 ºC for 48 hours), colonies were counted (cfu/mL) and the data were statistically analyzed by ANOVA and the Tukey test (α=0.05). Complete killing of C. albicans was observed after 18.0 J/cm² in association with 50 mg/L of PS. C. dubliniensis were inactivated after 18.0 J/cm² using 25 mg/L of PS. The inactivation of C. tropicalis was observed after photosensitization with 25 mg/L and subsequent illumination at 25.5 J/cm². For C. krusei, none of the associations between PS and light resulted in complete killing of this species. PDT proved to be effective for the inactivation of C. albicans, C. dubliniensis and C. tropicalis. In addition, reduction in the viability of C. krusei was achieved with some of the PS and light associations.

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

The inhibitory activity of crude extracts of Meliaceae and Rutaceae plants on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) enzyme from Trypanosoma cruzi was evaluated at 100 μg/mL. Forty-six extracts were tested and fifteen of them showed significant inhibitory activity (IA % > 50). The majority of the assayed extracts of Meliaceae plants (Cedrela fissilis, Cipadessa fruticosa and Trichilia ramalhoi) showed high ability to inhibit the enzymatic activity. The fractionation of the hexane extract from branches of C. fruticosa led to the isolation of three flavonoids: flavone, 7-methoxyflavone and 3',4',5',5,7-pentamethoxyflavone. The two last compounds showed high ability to inhibit the gGAPDH activity. Therefore, the assayed Meliaceae species could be considered as a promising source of lead compounds against Chagas' disease.

Metabólitos secundários das esponjas Aplysina fistularis e Dysidea sp. e atividade antituberculose da 11-cetofistularina-3

The present investigation reports the isolation of aeroplysinin-2, 2-(3,5-dibromo-4-methoxyphenyl)-N,N,N-trimethyletanamonium, 7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-trien-3-carboxylic acid and its methyl ester, 11-oxoaerothionin, aerothionin, 11-keto-12-hydroxyaerothionin, 11-ketofistularin-3 and fistularin-3 from Aplysina fistularis, as well as of furodysinin lactone and 9α,11α-epoxicholest-7-en-3β,5α,6α,10-tetrol-6-acetate from Dysidea sp. Although the extracts of both sponges displayed antituberculosis activity, only 11-ketofistularin-3 isolated from A. fistularis displayed antimycobacterial activity against Mycobacterium tuberculosis H34Rv, with MIC at 16 μg/mL and SI of 40, a result that reinforce that fistularin-3 derivatives are interesting leads for the development of antituberculosis drugs.

HPLC microfractionation of flavones and antioxidant (radical scavenging) activity of Saccharum officinarum L.

The antioxidant activity of sugarcane (Saccharum officinarum L.) juice towards DPPH reagent was determined (EC50) and the main compounds with radical scavenging activity in juice and leaves extracts were identified by HPLC-UV/PAD analysis combined with HPLC microfractionation monitored by TLC using β-carotene and DPPH as the detection reagents. In sugarcane leaves, luteolin-8-C-(rhamnosylglucoside) (1) was the most important compound with radical scavenging activity; in sugarcane juice, the flavones diosmetin-8-C-glucoside (2), vitexin (3) schaftoside (9), isoschaftoside (10) and 4',5'-dimethyl-luteolin-8-C-glucoside (11) were the most relevant compounds. The content of juice flavonoids (0.241 ± 0.001 mg total flavonoids/mL juice), comparable to other food sources of flavonoids, suggest the potential of sugarcane as a dietary source of natural antioxidants. However, the low antioxidant ability of sugarcane juice (EC50 = 100.2 ± 2.6 g L-1) also points to the need for further studies about the dietary intake of sugarcane flavonoids and its effects on human health.