Adroaldo Lunardelli

Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation.

Inflammation is a pivotal component of a variety of diseases, such as atherosclerosis and tumour progression. Various naturally occurring phytochemicals exhibit anti‐inflammatory activity and are considered to be potential drug candidates against inflammation‐related pathological processes. Capsicum baccatum L. var. pendulum (Willd.) Eshbaugh (Solanaceae) is the most consumed species in Brazil, and its compounds, such as capsaicinoids, have been found to inhibit the inflammatory process. However, the anti‐inflammatory effects of C. baccatum have not been characterized. Thus, this study was designed to evaluate the effects of C. baccatum juice in animal models of acute inflammation induced by carrageenan and immune inflammation induced by methylated bovine serum albumin. Pretreatment (30 min) of rats with pepper juice (0.25–2.0 g kg−1) significantly decreased leucocyte and neutrophil migration, exudate volume and protein and LDH concentration in pleural exudates of a pleurisy model. This juice also inhibited neutrophil migration and reduced the vascular permeability on carrageenan‐induced peritonitis in mice. C. baccatum juice also reduced neutrophil recruitment and exudate levels of pro‐inflammatory cytokines TNF‐α and IL‐1β in mouse inflammatory immune peritonitis. Furthermore, we demonstrated that the main constituent of C. baccatum juice, as extracted with chloroform, is capsaicin. In agreement with this, capsaicin was able to inhibit the neutrophil migration towards the inflammatory focus. To our knowledge, this is the first demonstration of the anti‐inflammatory effect of C. baccatum juice and our data suggest that this effect may be induced by capsaicin. Moreover, the anti‐inflammatory effect induced by red pepper may be by inhibition of pro‐inflammatory cytokine production at the inflammatory site.

Immunomodulatory effect of fructose-1,6-bisphosphate on T-lymphocytes

Sepsis remains an important and life-threatening problem, and is the most common cause of death in the intensive care unit. One promising therapeutic candidate for protection against injury in sepsis is fructose-1,6-bisphosphate (FBP), a high-energy glycolytic pathway intermediate. The objective of the study was to establish a role for FBP on the immune system, especially in lymphocyte proliferation. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy humans by gradient centrifugation. T-lymphocytes were stimulated for 96 h with phytohemagglutinin (PHA) and varying concentration of FBP. Fructose-1,6-bisphosphate at concentrations between 1.2 and 10 mM decreased proliferation of T-lymphocytes and reduced the viability only at concentrations 5.0 and 10 mM. The levels of soluble IL-2 receptor were reduced at FBP concentrations between 1.2 and 10 mM. In conclusion, this study demonstrates that FBP has important effect on immunomodulatory and this result can be correlated with the protection against injury in sepsis.

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.

The effects of fructose-1,6-bisphosphate and dexamethasone on acute inflammation and T-cell proliferation

Abstract.Objective and designChronic glucocorticoid treatment is associated with pharmacological resistance. We investigated the auxiliary effects of fructose-1,6-bisphosphate (FBP) on dexamethasone (DEX)-related modulation of inflammation and T-cell proliferation.MethodsAcute inflammation (pleurisy) was induced by injection of carrageenan into the pleural cavity of rats that were treated in vivo with DEX s. c. and FBP i. p. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to FBP and DEX was evaluated in vitro.ResultsFBP and DEX reduced the exudate volume, protein concentration and neutrophils in the pleural cavity. However no synergistic effects were observed when these compounds were tested simultaneously. In contrast, both compounds dose-dependently and synergistically suppressed T-cell proliferation.ConclusionThese data suggest that FBP may be beneficial as auxiliary drug for the treatment of patients with acquired glucocorticoid resistance.

Influência da dieta na concentração sérica de triglicerídeos

BACKGROUND: Elevated levels of triglycerdes in the serum are associated with patologicals conditions that they accelerate to aterosclerose, beyond they evidences will exist of that to hypertrigliceridemia is an independent factor of risk for illnesses coronarias therefore I contributed for the cardiopatias by an effect aterogenico straight of the lipoproteinas rich in triglicerideos. Very big variations in the dosage of the colesterol and triglicerides they limit sweats clinical utilization. Those variations can be analytic, when related to metodologia and procedures utilized by the laboratories, and pre analytic, when related to factors intrinsecos of the individual. Objectives: Using the same approach laboratorial, analyzed itself possible alterations in the levels lipidicos of the patients in order to question to true validade of that the fast of 12 previous hours to the puncao be sufficient for that can be carried out trustworthy dosages with the profile of the patient. METHODS: They were analyzed serum of 29 patients, reaped in two distinct days; in the Monday and in the Thursday from the same week. RESULTS: We be able to observe variations on the occasion of the dosage of triglicerideos in peculiar days from the week, being that the levels of such parameter in the Monday are presented more elevated that in the Thursday, even that the sick one I have done a rigorous fast of 12 hours before of both you collect them. The colesterol gross, the HDL, the LDL and the VLDL they were not shown with significant statistical variation. Discussion: Being like this, the fast recommended of 12 hours is not sufficient to relate the real profile lipidico of the patient.

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

Abstract 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 μg/mL and 0.1–10.0 μg/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 μg/mL, 95% limits of agreement from –0.65 to 2.80 μg/mL). Conclusions: This difference may be decisive for the therapy. In some cases, this may affect the individual dosage adjustment and subsequent treatment. Clin Chem Lab Med 2009;47:458–63.

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.

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.

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.