Dapsone Prevents Allodynia and Hyperalgesia and Decreased Oxidative Stress After Spinal Cord Injury in Rats.

STUDY DESIGN: Prospective longitudinal experimental study. OBJECTIVE: We evaluate the effect of dapsone on tactile allodynia and mechanical hyperalgesia and to determine its anti-oxidant effect in a spinal cord injury (SC) model in rats. SUMMARY OF BACKGROUND DATA: Neuropathic pain (NP) as result of traumatic spinal cord injury is a deleterious medical condition with temporal or permanent time-course. Painful stimuli trigger a cascade of events that activate the N-methyl-D-aspartate (NMDA) receptor, inducing an increase in oxidative stress. Since there is no effective treatment for this condition, dapsone (4,4'diaminodiphenylsulfone) is proposed as potential treatment for NP. Its anti-oxidant, neuroprotective, and anti-inflammatory properties have been documented, however, there is no evidence regarding its use for treatment of NP induced by SCI. METHODS: In this study, we evaluated the anti-allodynic and anti-hyperalgesic effect of dapsone as preventive or acute treatment after NP was already established. Furthermore, participation of oxidative stress was evaluated by measuring lipid peroxidation (LP) and glutathione concentration (GSH) in rats with SCI. RESULTS: Acute treatment with dapsone (3.1-25 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH in the injured tissue 15 days after the injury was produced. On the other hand, preventive treatment (3 h post-injury, once daily for 3 days) with dapsone (3.1-25 mg/kg, i.p.) yielded similar results. CONCLUSION: The findings suggest that the anti-nociceptive effect of dapsone is regulated through the decrease of oxidative stress and the excitotoxicity is associated with the activation of NMDA receptors.Level of Evidence: N/A.

Amantadine prevented hypersensitivity and decreased oxidative stress by NMDA receptor antagonism after spinal cord injury in rats.

BACKGROUND: Neuropathic pain (NP) after spinal cord injury (SCI) is a disabling condition, without an effective treatment. Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors and oxidative stress have been reported to be associated with pain development. Amantadine, an NMDA receptor antagonist, has been proposed as a potential therapy for NP. However, its use has not been tested for NP after SCI. METHODS: To produce SCI, 120 female Wistar rats were used, a contusion injury to the T10 and T12 thoracic vertebrae was performed from heights of 6.25 mm and 12.5 mm. Nociceptive behaviour, was evaluated with the use of von Frey filaments for 31 days. The final products of lipid peroxidation (LP) and concentration of reduced glutathione (GSH) in the injured tissue were quantified by fluorescence spectrophotometry. The antinociceptive effect of the acute (15 days after the injury) and chronic (once daily for three days immediately after the injury) with amantadine (6.25-50 mg/Kg. I.p.) was determined. Finally, the LP and GSH were quantified in the injured tissue. RESULTS: Acute treatment with amantadine reduced nociceptive behaviour. Concomitantly, LP was decreased by Amantadine treatment while GSH increased in the injured tissue. Similar effects were observed with chronic treatment with amantadine. CONCLUSIONS: Data from this study suggested that the antinociceptive effects of amantadine treatment are modulated through oxidative stress and excitotoxicity reduction associated with N-methyl-D-aspartate receptors activation. SIGNIFICANCE: This study suggests that acute treatment with amantadine decreases hypersensitivity threshold and frequency of hypersensitivity response in a dose-dependent manner, in rats with SCI, by decreasing oxidative stress. Since amantadine is an easily accessible drug and has fewer adverse effects than current treatments for hypersensitivity threshold and frequency of hypersensitivity response, amantadine could represent a safe and effective therapy for the treatment of neuropathic pain. However, further research is required to provide evidence of the effectiveness and feasibility.

Anti-inflammatory activity of Jefea gnaphalioides (a. gray), Astereaceae.

BACKGROUND: Inflammation is a symptom associated with many diseases. This symptom is treated with steroidal and non-steroidal anti-inflammatory drugs, which can cause severe side effects when used as long-term treatments. Natural products are an alternative source of new compounds with anti-inflammatory activity. Jefea gnaphalioides (Astereaceae) (A. Gray) is a plant species used to treat inflammatory problems, in Mexico. This study determined the anti-inflammatory activity and the composition of the methanol extract of Jefea gnaphalioides (MEJG). METHODS: The extract was obtained by heating the plant in methanol at boiling point for 4 h, and then the solvent was evaporated under vacuum (MEJG). The derivatization of the extract was performed using Bis-(trimethylsilyl) trifluoroacetamide, and the composition was determined by GC-MS. Total Phenols and flavonoids were determined by Folin-Ciocalteu AlCl3 reaction respectively. The antioxidant activity of MEJG was determined by DPPH method. The acute and chronic anti-inflammatory effects were evaluated on a mouse ear edema induced with 12-O-Tetradecanoylphorbol-13-acetate (TPA). Acute oral toxicity was tested in mice at doses of MEJG of 5000, 2500 and 1250 mg/kg. The levels of NO, TNF-α, IL-1ß and IL-6 were determinate in J774A.1 macrophages stimulated by Lipopolysaccharide. The production of inflammatory interleukins was measured using commercial kits, and nitric oxide was measured by the Griess reaction. RESULTS: The anti-inflammatory activity of MEJG in acute TPA-induced ear edema was 80.7 ± 2.8%. This result was similar to the value obtained with indomethacin (IND) at the same dose (74.3 ± 2.8%). In chronic TPA-induced edema at doses of 200 mg/kg, the inhibition was 45.7%, which was similar to that obtained with IND (47.4%). MEJG have not toxic effects even at a dose of 5000 mg/kg. MEJG at 25, 50, 100 and 200 µg/mL decreased NO, TNF-α, IL-1ß and IL-6 production in macrophages stimulated with LPS. The major compounds in MEJG were α-D-Glucopyranose (6.71%), Palmitic acid (5.59%), D-(+)-Trehalose (11.91%), Quininic acid (4.29%) and Aucubin (1.17%). Total phenolic content was 57.01 mg GAE/g and total flavonoid content was 35.26 mg QE/g MEJG had antioxidant activity. CONCLUSIONS: MEJG has anti-inflammatory activity.

Quantum Reality in the Selective Reduction of a Benzofuran System.

Two 2,3-disubstituted benzofurans (1 and 2), analogs of gamma-aminobutyric acid (GABA), were synthesized to obtain their 2,3-dihydro derivatives from the Pd/C-driven catalytic reduction of the double bond in the furanoid ring. The synthesis produced surprising by-products. Therefore, theoretical calculations of global and local reactivity were performed based on Pearson's hard and soft acids and bases (HSAB) principle to understand the regioselectivity that occurred in the reduction of the olefinic carbons of the compounds. Local electrophilicity (ωk) was the most useful parameter for explaining the selectivity of the polar reactions. This local parameter was defined with the condensed Fukui function and redefined with the electrophilic (Pk+) Parr function. The similar patterns of both resulting sets of values helped to demonstrate the electrophilic behavior (soft acid) of the olefinic carbons in these compounds. The theoretical calculations, nuclear magnetic resonance, and resonance hybrids showed the moieties in each compound that are most susceptible to reduction.

Anti-inflammatory activity of standardized dichloromethane extract of Salvia connivens on macrophages stimulated by LPS.

CONTEXT: A previous study demonstrated that the chloroform extract of Salvia connivens Epling (Lamiaceae) has anti-inflammatory activity. OBJECTIVE: Identification of the active components in the dicholorometane extract (DESC), and, standardization of the extract based in ursolic acid. MATERIAL AND METHODS: DESC was prepared by percolation with dichlromethane and after washed with hot hexane, its composition was determined by CG-MS and NMR, and standardized by HPLC. The anti-inflammatory activity was tested on acute TPA-induced mouse ear oedema at doses of 2.0 mg/ear. The cell viability of macrophages was evaluated by MTT method, and pro- and anti-inflammatory interleukin levels were measured using an ELISA kit. RESULTS: Ursolic acid, oleanolic acid, dihydroursolic acid and eupatorin were identified in DESC, which was standardized based on the ursolic acid concentration (126 mg/g). The anti-inflammatory activities of DESC, the acid mixture, and eupatorin (2 mg/ear) were 60.55, 57.20 and 56.40% inhibition, respectively, on TPA-induced ear oedema. The IC50 of DESC on macrophages was 149.4 µg/mL. DESC (25 µg/mL) significantly reduced TNF-α (2.0-fold), IL-1ß (2.2-fold) and IL-6 (2.0-fold) in macrophages stimulated with LPS and increased the production of IL-10 (1.9-fold). DISCUSSION: Inflammation is a basic response to injuries, and macrophages are involved in triggering inflammation. Macrophage cells exhibit a response to LPS, inducing inflammatory mediators, and DESC inhibits the biosynthesis of the pro-inflammatory and promote anti-inflammatory cytokines. CONCLUSION: DESC has an anti-inflammatory effect; reduced the levels of IL-1ß, Il-6 and TNF-α; and increases IL-10 in macrophages stimulated with LPS. Ursolic acid is a good phytochemical marker.

In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole.

Effects of kramecyne on LPS induced chronic inflammation and gastric ulcers.

Preclinical Research Krameria cytisoides is used for the treatment of inflammation, stomach pain, and gastric ulcers. The active ingredient from this plant is a peroxide, kramecyne (KACY) which has anti-inflammatory effects. The aim of the present study was to evaluate the anti-inflammatory activities of KACY in lipopolysaccharide (LPS)-induced systemic chronic inflammation in mice for 60 days, using dexamethasone (DEX) as the positive control, vehicle (the LPS group) as the negative control and the control group (mice without inflammation). KACY did not affect survival, body weight or relative organ weight in mice but it: decreased nitric oxide (NO) production by 68%; prostaglandin E2 (PGE2 ) by 67%; increased release of anti-inflammatory cytokine IL-10 (2.0-fold), and reduced production of the proinflammatory cytokines, IL-6 (2.0-fold), IL-1ß (2.4-fold), and TNF-α (2.0-fold). Furthermore, the gastroprotective effects of KACY in mice were evaluated in an ethanol-induced gastric ulcer model. The results showed that KACY at 50 and 100 mg/kg exerted gastroprotective effects with similar activity to 50 mg/kg ranitidine. In gastric tissues, KACY decreased the level of malondialdehyde (MDA) but increased the catalase (CAT) activity. KACY have potential for the treatment of chronic inflammatory diseases due its similar activity to that of DEX. It also has gastroprotective effects.

Synthesis, antinociceptive and anti-inflammatory effects of porphyrins.

Porphyrins are natural compounds with several biological activities. We report the synthesis and the evaluation of the anti-inflammatory and antinociceptive effects of 4 porphyrins: 5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetra(4'-fluorophenyl)porphyrin (TpFPP), 5,10,15,20-tetra(4'-chlorophenyl)porphyrin (TpClPP), and 5,10,15,20-tetra(4'-bromophenyl)porphyrin (TpBrPP). The in vitro anti-inflammatory effects were evaluated on heat-induced hemolysis. The antinociceptive effects were evaluated using the hot plate and formalin tests. The in vivo anti-inflammatory assays were tested on the acute and chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema. The anti-arthritic effects were evaluated using carrageenan kaolin induced arthritis (CKIA). All porphyrins inhibited hemolysis with similar potency than naproxen (NPX). In the antinociceptive tests, all porphyrins tested at 200mg/kg showed similar effects compared to 100mg/kg NPX. In the in vivo anti-inflammatory acute assay, only three porphyrins (TPP, TpFPP and TpBrPP) decreased inflammation with similar activity than 2mg/ear indomethacin (IND). Further anti-inflammatory experiments were carried out with TPP, TpFPP and TpBrPP. In the in vivo anti-inflammatory chronic assay, porphyrins decreased inflammation with similar activity than 8mg/kg IND. Porphyrins tested at 200mg/kg showed anti-arthritic effects. The antinociceptive, anti-inflammatory and arthritic activities of porphyrins suggest that these compounds might be a good alternative for the treatment of inflammatory diseases.

Antidiarrheal activity of 19-deoxyicetexone isolated from Salvia ballotiflora Benth in mice and rats.

The antidiarrheal properties of 19-deoxyicetexone, a diterpenoid isolated from Salvia ballotiflora were evaluated on castor oil-, arachidonic acid (AA)- and prostaglandin (PGE2)-induced diarrhea in rodent models. The structure of 19-deoxyicetexone was determined by X-ray crystallography, mass spectrometry (EI-MS), as well as ultraviolet (UV-Vis), infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. This compound significantly and dose-dependently reduced frequency of stooling in castor oil-induced diarrhea, and at dose of 25 mg/kg it also inhibited diarrhea induced with AA, while it had no effect on PGE2-induced diarrhea. This compound at doses of 25 mg/kg also diminished castor oil-induced enteropooling and intestinal motility, and inhibited the contraction of the rats' ileum induced by carbachol chloride at a concentration of 100 µg/mL. 19-Deoxyicetexone did not present acute toxicity at doses of 625 mg/kg. Its antidiarrheal activity may be due to increased reabsorption of NaCl and water and inhibition of the release of prostaglandins, gastrointestinal motility and fluid accumulation in the intestinal tracts of rats. These findings suggest that 19-deoxyicetexone may be used in the treatment of diarrhea, although more studies must be carried out to confirm this.

Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine derivatives.

BACKGROUND: Imidazo[1,2-a]pyridines and pyrimidines are important organic fluorophores which have been investigated as biomarkers and photochemical sensors. The effect on the luminescent property by substituents in the heterocycle and phenyl rings, have been studied as well. In this investigation, series of 3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines were synthesized and evaluated in relation to fluorescence emission, based upon the hypothesis that the hydroxymethyl group may act as an enhancer of fluorescence intensity. RESULTS: Compounds of both series emitted light in organic solvents dilutions as well as in acidic and alkaline media. Quantitative fluorescence spectroscopy determined that both fused heterocycles fluoresced more intensely than the parent unsubstituted imidazo[1,2-a]azine fluorophore. In particular, 3-hydroxymethyl imidazo[1,2-a]pyridines fluoresced more intensely than 3-hydroxymethyl imidazo[1,2-a]pyrimidines, the latter emitting blue light at longer wavelengths, whereas the former emitted purple light. CONCLUSION: It was concluded that in most cases the hydroxymethyl moiety did act as an enhancer of the fluorescence intensity, however, a comparison made with the fluorescence emitted by 2-aryl imidazo[1,2-a]azines revealed that in some cases the hydroxymethyl substituent decreased the fluorescence intensity.

Kramecyne--a new anti-inflammatory compound isolated from Krameria cytisoides.

In the present work we describe the structure and anti-inflammatory activity of a new compound, kramecyne, isolated from a methanol extract of Krameria cytisoides (Krameriaceae). The structure of kramecyne was determined by IR, NMR, MS, and elemental analysis, which indicated that the structure corresponded to a hexamer of cyclic peroxide monomers. This compound exhibited good anti-inflammatory activity in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema (51.8 ± 6.9% inhibition) and carrageenan-induced rat paw edema models at doses of 50 mg/kg. The compound significantly reduced edema to 63.1% after 1.0 h, and the effect was unchanged for 5 h. Kramecyne did not present acute toxicity, even at doses of 5,000 mg/kg.

Design and synthesis of anti-MRSA benzimidazolylbenzene-sulfonamides. QSAR studies for prediction of antibacterial activity.

A series of benzimidazolylbenzenesulfonamide compounds containing electron-releasing and electron-withdrawing substituents were synthesized and tested for their in vitro antibacterial activity. Two BZS compounds showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Bacillus subtilis. Quantitative studies of their structure-activity relationship using a simple linear regression analysis were applied to explore the correlation between the biological activity and the charges on acidic hydrogen atoms in the synthesized compounds.

Detección de suero de quesería en leches ultrapasteurizadas mexicanas mediante la cuarta derivada del espectro de absorción / Rennet whey solids detection in Mexican ultrapasteurized milk using fourth derivative absortion spectrum

Presence of rennet whey solids in ultrapasteurized milk (UHT) commercialized in Mexico City was determined using fourth derivative of absorption spectrum method, which allows to know the variation in whey protein/total protein ratio (WP/TP). The quantification of WP/TP ratio was used as an indicator of adulteration with rennet whey solids. The method was standardized to evaluate the accuracy, linearity and repeatability by rennet whey addition in concentrations between 0-15%, in raw milk. Thirty samples of skim ultrapasteurized milk were analyzed during September, October and November; found values were compared to the ones of raw milk added with rennet whey solids (0-15%, in levels of 2.5%). A marginal difference was found in the WP/TP ratio for the 0% concentration between the two types of milk, while the rest of the concentrations showed a high significance (P < 0.01). Values above 13.5% of WP/TP showed rennet whey solids addition; 36.7% of the UHT milk samples were between 5% and 12% positive to rennet whey solids addition. The results indicated that fourth derivative of the absorption spectrum of the WP/TP ratio was a sensitive indicator to rennet whey solids additions.

Se determinó la presencia de suero de quesería en leches ultrapasteurizadas (UHT) comercializadas en la Ciudad de México mediante el método de la cuarta derivada del espectro de absorción, el cual permite conocer la variación de la relación proteínas de suero/proteína total (PS/PT). La cuantificación de la relación PS/PT se utilizó como indicador de la adulteración con suero de quesería. El método fue estandarizado evaluando la exactitud, linealidad y repetibilidad mediante la adición de suero en concentraciones entre 0%-15% a leche cruda. Se analizaron 30 muestras de leche ultrapasteurizada descremada durante septiembre, octubre y noviembre; los valores encontrados se contrastaron con los de leche cruda adicionada con suero de quesería (0%-15%, en niveles de 2.5%. Se encontró una diferencia marginal en la relación PS/PT para la concentración 0% entre los dos tipos de leche, mientras que el resto de las concentraciones mostró una significancia alta (P < 0.01). Valores por encima de 13.5% de PS/PT expresaron adición de suero; 36.7% de las muestras de leche UHT fueron positivas a la adición de suero entre 5% y 12%. Los resultados indicaron que la cuarta derivada del espectro de absorción de la relación PS/PT fue un indicador sensible a adiciones de suero de quesería.

Chemical composition and antifungal activity of essential oil of Chrysactinia mexicana gray.

The chemical composition of the essential oil of Chysactinia mexicana was analyzed by gas chromatography-mass spectrometry. Seventeen compounds were characterized; eucalyptol (41.3%), piperitone (37.7%), and linalyl acetate (9.1%) were found as the major components. The essential oil of leaves and piperitone completely inhibited Aspergillus flavus growth at relatively low concentrations (1.25 and 0.6 mg/mL, respectively).

Actividad hipoglucemiante de Bouvardia terniflora, Brickellia veronicaefolia y parmentiera edulis / Hypoglycemic activity of Bouvardia terniflora, Brickellia veronicaefolia and parmentiera edulis

Objetivo. Evaluar la actividad hipoglucemiante de los extractos de hexano, cloroformo y metanol de Brickellia veronicaefolia, Bouvardia terniflora y Parmentiera edulis. Material y métodos. Se probaron los extractos de las plantas (100, 200 y 300 mg/kg, vía intraperitoneal) en ratones normoglucémicos y con diabetes inducida con aloxana. Resultados. La administración de 300 mg/kg de los extractos clorofórmicos de P. edulis, B. terniflora y hexánico de B. veronicaefolia en ratones diabéticos disminuye el nivel de glucosa sanguínea en 43.75, 58.56 y 72.13 por ciento, respectivamente. Estos extractos (300 mg/kg), administrados en ratones normoglucémicos, reducen la glucosa sanguínea en 29.61, 33.42 y 39.84 por ciento, respectivamente. Conclusiones. Con este estudio se confirma la actividad hipoglucemiante de estas plantas usadas en la medicina tradicional para el tratamiento de las diabetes