Datura stramonium Flowers as a Potential Natural Resource of Bioactive Molecules: Identification of Anti-Inflammatory Agents and Molecular Docking Analysis.

The present study investigated the antioxidant, antibacterial, antiviral and anti-inflammatory activities of different aerial parts (flowers, leaves and seeds) of Datura stramonium. The plant material was extracted with 80% methanol for about 24 h. The sensitivity to microorganisms analysis was performed by the microdilution technique. Antioxidant tests were performed by scavenging the DPPH and ABTS radicals, and by FRAP assay. Anti-inflammatory activity was evaluated through the inhibition of nitric oxide production in activated macrophage RAW 264.7 cells. Cell viability was assessed with an MTT assay. Results show that the flower extract revealed a powerful antimicrobial capacity against Gram-positive bacteria and strong antioxidant and anti-inflammatory activities. No significant cytotoxicity to activated macrophages was recorded. High resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analysis identified two molecules with important anti-inflammatory effects: 12α-hydroxydaturametelin B and daturametelin B. Molecular docking analysis with both pro-inflammatory agents tumor necrosis factor alpha and interleukin-6 revealed that both compounds showed good binding features with the selected target proteins. Our results suggest that D. stramonium flower is a promising source of compounds with potential antioxidant, antibacterial, and anti-inflammatory activities. Isolated withanolide steroidal lactones from D. stramonium flower extract with promising anti-inflammatory activity have therapeutic potential against inflammatory disorders.

Use and effectiveness of propolis on chronic periodontitis: a systematic review / Uso y efectividad del propóleo en periodontitis crónica: una revisión sistemática

Abstract The aim of this study was to determine the effect of propolis on non- surgical periodontal therapy in patients with chronic periodontitis (CP) as it appears in the recent literature. Propolis is a natural and biocompatible resinous substance that has shown, by means of several scientific studies, to possess medicinal properties such as antimicrobial, healing, anesthetic, anti-inflammatory, and analgesic, among others. There are several studies that have reported the use of propolis as a non- surgical treatment of CP, its comparison with other antimicrobials, and the improvement of clinical and microbiological parameters with scaling and root planing (SRP). A bibliographic search was conducted in the PubMed, Google Scholar, Web of Science, and Science Direct databases up to 2021. The results showed that there are very few reports focused on clinical studies; however, according to the analyzed data, propolis could be a good adjuvant for the treatment of patients with chronic periodontitis compared to the conventional treatment (SRP).

Resumen El objetivo de este estudio fue determinar el efecto del propóleo sobre la terapia periodontal no quirúrgica en pacientes con periodontitis crónica (PC) en la literatura reciente. El propóleo es una sustancia resinosa natural y biocompatible que ha sido demostrado a través de varios estudios científicos que posee propiedades medicinales como antimicrobianas, cicatrizantes, anestésicas, antiinflamatorias, analgésicas, entre otras. Existen varios estudios que han reportado el uso del propóleo como tratamiento no quirúrgico de la PC y su comparación con otros antimicrobianos y la mejora de los parámetros clínicos y microbiológicos con el raspado y alisado radicular (SRP). Se realizó una búsqueda bibliográfica en las bases de datos directas de PubMed, Google Scholar, Web of Science y Science hasta el 2021. Los resultados muestran que existen muy pocos reportes enfocados a estudios clínicos, sin embargo, según los datos analizados, el propóleo podría ser un buen adyuvante para el tratamiento de pacientes con periodontitis crónica en comparación con el tratamiento convencional (SRP).

Oximetría de pulso y su eficacia para diagnosticar vitalidad pulpar / Pulse oximetry and its use in diagnosing pulp vitality

Objetivo: Identificar y analizar en la literatura científica reciente el uso de la oximetría de pulso como método diagnóstico de vitalidad pulpar. Metodología: En este trabajo se llevó a cabo una revisión de la literatura en las plataformas de PubMed y Google Académico, en la cual se analizó el uso de la oximetría de pulso en el diagnóstico y monitoreo odontológico del estado pulpar. Resultados: Después de una exhaustiva revisión, y de acuerdo con los criterios de inclusión y exclusión, se analizaron 21 artículos. La mayoría de los trabajos consideran la oximetría de pulso un método alternativo de diagnóstico indoloro, seguro y eficaz; sin embargo, la adaptación de un instrumento de uso exclusivo odontológico es necesaria para una medición exacta de la saturación de oxígeno en la pulpa dental. Los avances tecnológicos en el campo clínico de la odontología nos han llevado a la búsqueda de nuevas técnicas diagnósticas clínicas para mejorar la atención y los tratamientos de los pacientes que acuden día con día a recibir una consulta odontológica. Conclusiones: En los últimos años la oximetría de pulso ha demostrado ser una herramienta de diagnóstico eficaz para el diagnóstico de la vitalidad pulpar. El análisis de los artículos incluidos en esta revisión concluye que la oximetría de pulso es una técnica innovadora que puede ser utilizada como una herramienta diagnóstica adyuvante en el diagnóstico de la vitalidad pulpar (AU)

Objective: To identify and analyze in the recent scientific literature the use of pulse oximetry as a diagnostic method for pulp vitality. Methodology: In this work, a literature review was carried out on the PubMed and Google Scholar platforms in which the use of pulse oximetry in the dental diagnosis and monitoring of pulp status was analyzed. Results: After an exhaustive review and in accordance with the inclusion and exclusion criteria, 21 articles were analyzed. Most of the studies consider pulse oximetry an alternative method of painless, safe and effective diagnosis, however, the adaptation of an instrument for exclusive dental use is necessary for an exact measurement of the oxygen saturation in the dental pulp. Technological advances in the clinical field of dentistry have led us to search for new clinical diagnostic techniques to improve the care and treatment of patients who come every day to receive a dental consultation. Conclusions: In recent years, pulse oximetry has proven to be an effective diagnostic tool for the diagnosis of pulp vitality. The analysis of the articles included in this review concludes that pulse oximetry is an innovative technique that can be used as an adjunct diagnostic tool in the diagnosis of pulp vitality (AU)

Identification of α-Amylase and α-Glucosidase Inhibitors and Ligularoside A, a New Triterpenoid Saponin from Passiflora ligularis Juss (Sweet Granadilla) Leaves, by a Nuclear Magnetic Resonance-Based Metabolomic Study.

The leaves of Passiflora ligularis Juss (known as sweet granadilla for its edible fruits) are a crop byproduct that is discarded. With the aim of contributing to give value-added products from these crop by-side products to farmers of Colombian Andes, we carried out a 1H-NMR-metabolomics analysis of polar extracts from leaves collected in three locations and stored in two conditions in order to identify glucosyl-hydrolase inhibitors. Variations in the metabolic profile and the bioactivity among samples were analyzed by orthogonal partial least square discriminant analysis. Thus, 1H-NMR signals related to polyphenolic compounds, saponins, and amino acids were correlated with higher inhibitory activities. Moreover, a targeted NMR and HPLC-MS/MS analysis allowed the identification of 14 polyphenolic compounds and the structural characterization of a new triterpenoid saponin, ligularoside A. The measurements of IC50 values for α-amylase and α-glycosidase inhibitors allowed the identification of quercetin-3-O-ß-glucoside, kaempferol-3-O-ß-glucoside, and ligularoside A as the most active compounds. These results suggest that P. ligularis leaves are a source of glucosyl-hydrolase inhibitors and lay the foundation for exploring additional applications.

Hydrogel-embedded gold nanorods activated by plasmonic photothermy with potent antimicrobial activity.

Plasmonic photothermal therapy (PPTT) has been used as an alternative to chemotherapy for the elimination of resistant microorganisms; however, its in situ evaluation has not been well studied. In the present study, we assessed the antimicrobial activity of a chitosan-based hydrogel embedded with gold nanorods (Ch/AuNRs) using a low power infrared diode laser. The antibacterial activity was measured in both Gram-positive and -negative strains, including clinical isolates of multidrug-resistant pathogens. The cytotoxic effect, cellular proliferation, and the expression of the pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines were quantified in a murine model of macrophages. Results showed a potent antimicrobial activity of the Ch/AuNRs with MICs ≤4 µg/mL, very low cytotoxicity with cell viability above 80%, and the macrophage proliferation was not affected for a period of 48 h. These results suggest that our Ch/AuNR-embedded hydrogel could be an option to locally control chronic nosocomial infections using PPTT.

Antioxidant supplements as a novel mean for blocking recurrent heat stress-induced kidney damage following rehydration with fructose-containing beverages.

Recently repeated heat stress and dehydration have been reported to cause oxidative stress and kidney damage that is enhanced by rehydrating with fructose solutions. We hypothesized that antioxidants might provide a novel way to prevent kidney damage. To test this hypothesis, mild heat stress was induced by exposing rats to 37 °C during 1 h in a closed chamber. The supplementation with water-soluble antioxidants (Antiox), ascorbic acid 1% plus N-acetyl cysteine 600 mg/L was done either in the 10% fructose 2 h rehydration fluid immediately after heat stress (Fructose 10% + Antiox), and/or in the tap water (Water + Antiox) for the remainder of the day, or in both fluids. After 4 weeks, control rats exposed to heat with fructose rehydration developed impaired renal function, tubular injury, intrarenal oxidative stress, a reduction in Nrf2-Keap1 antioxidant pathway, stimulation of vasopressin and the intrarenal polyol-fructokinase pathway. In contrast, dosing the antioxidants in the tap water (i.e., before the heat exposure and rehydration with fructose) preserved renal function, prevented renal tubule dysfunction and avoided the increase in systemic blood pressure. These effects were likely due to the amplification of the antioxidant defenses through increased Nrf2 nuclear translocation stimulated by the antioxidants and by the prevention of polyol fructokinase pathway overactivation. More studies to understand the mechanisms implicated in this pathology are warranted as there is recent evidence that they may be operating in humans as well.

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3ß-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis.

Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3ß-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate.

BACKGROUND: Heat stress and rhabdomyolysis are major risk factors for the occurrence of repeated acute kidney injury in workers exposed to heat and strenuous work. These episodes, in turn, may progress to chronic kidney disease. OBJECTIVE: The purpose of this study was to test the effect of allopurinol (AP) and sodium bicarbonate on the kidney injury induced by recurrent heat stress dehydration with concomitant repeated episodes of rhabdomyolysis. METHODS: The model consisted of heat stress exposure (1 h, 37°C) plus rhabdomyolysis (R) induced by repetitive IM injections of glycerol (7.5 mL/kg BW days) in the rat. In addition, to replicate the human situation, uricase was inhibited (oxonic acid [OA] 750 mg/K/d) to increase uric acid (UA) levels. Additional groups were treated either with AP 150 mg/L, n = 10, bicarbonate (BC; 160 mM, n = 10), or both (AP + BC, n = 10) in drinking water. We also included 2 control groups consisting of normal controls (N-Ref, n = 5) and uricase-inhibited rats (OA, n = 5) that were not exposed to heat or muscle injury. Groups were studied for 35 days. RESULTS: Uricase-inhibited rats exposed to heat and rhabdomyolysis developed pathway and increased intrarenal oxidative stress and inflammasome activation. Kidney injury could be largely prevented by AP, and also BC, although the treatments were not synergistic. CONCLUSION: Increased levels of UA may play an important role in the renal alterations induced by heat stress and continuous episodes of rhabdomyolysis. Therefore, treatments aimed to reduce hyperuricemia may help to decrease the renal burden in these conditions. Clinical trials are suggested to test whether this is also true in humans.

Experimental heat stress nephropathy and liver injury are improved by allopurinol.

An epidemic of chronic kidney disease (CKD) has been observed in Central America among workers in the sugarcane fields. One hypothesis is that the CKD may be caused by recurrent heat stress and dehydration, and potentially by hyperuricemia. Accordingly, we developed a murine model of kidney injury associated with recurrent heat stress. In the current experiment, we tested whether treatment with allopurinol (a xanthine oxidase inhibitor that reduces serum urate) provides renal protection against recurrent heat stress and dehydration. Eight-week-old male C57BL/6 mice were subjected to recurrent heat stress (39.5°C for 30 min, 7 times daily, for 5 wk) with or without allopurinol treatment and were compared with control animals with or without allopurinol treatment. Mice were allowed ad libitum access to normal laboratory chow (Harlan Teklad). Kidney histology, liver histology, and renal function were examined. Heat stress conferred both kidney and liver injury. Kidneys showed loss of proximal tubules, infiltration of monocyte/macrophages, and interstitial collagen deposition, while livers of heat-stressed mice displayed an increase in macrophages, collagen deposition, and myofibroblasts. Allopurinol provided significant protection and improved renal function in the heat-stressed mice. The renal protection was associated with reduction in intrarenal uric acid concentration and heat shock protein 70 expression. Heat stress-induced renal and liver injury can be protected with allopurinol treatment. We recommend a clinical trial of allopurinol for individuals developing renal injury in rural areas of Central America where the epidemic of chronic kidney disease is occurring.

La escucha: elemento fundamental en la atención espiritual del cuidado paliativo / Listening: A Fundamental Element in the Spiritual Care of Palliative Care / A escuta: elemento fundamental no atendimento espiritual do cuidado paliativo

Resumen Los cuidados paliativos buscan ofrecer una atención holística para brindar una mejor calidad de vida a los enfermos, especialmente cuando se aproximan al fin de su existencia. Profundizar en la dimensión espiritual de la persona humana resulta atractivo puesto que ofrece respuestas al sentido de la vida. Se ha constatado que la atención espiritual aporta grandes beneficios para el paciente. Por eso, en este trabajo hemos querido profundizar en la importancia de la dimensión espiritual en los cuidados paliativos; se destaca la actitud de la escucha como pieza clave de dicha atención espiritual, lo que evidencia que el burnout de los médicos es el principal obstáculo para potenciar la escucha como una adecuada disposición que resulte consoladora y sanadora.

Abstract Palliative care seeks to offer holistic care in order to provide a better quality of life for the sick, particularly when they are nearing the end of their existence. Delving into the spiritual dimension of the human person is attractive, since it offers answers to the meaning of life. It has been found that spiritual care brings great benefits to patients. That is why in this paper we wish to delve into the importance of the spiritual dimension in palliative care; we highlight the act of listening as a key piece of spiritual care, which shows that the doctors' burnout is the main obstacle to enhance listening as a suitable provision that is both comforting and healing.

Resumo Os cuidados paliativos buscam oferecer uma atenção holística para proporcionar uma melhor qualidade de vida aos doentes, especialmente quando se aproximam ao fim de sua existência. Aprofundar na dimensão espiritual da pessoa humana acaba sendo atrativo, posto que oferece respostas ao sentido da vida. Foi constatado que o atendimento espiritual traz grandes benefícios para o paciente. É por isso que neste trabalho quisemos nos aprofundar na importância da dimensão espiritual nos cuidados paliativos; a atitude da escuta se destaca como peça-chave de tal atendimento espiritual, o que evidencia que o burnout dos médicos é o principal obstáculo para potencializar a escuta como uma disposição adequada que resulte consoladora e sanadora.

Relationship between hyperspectral indices, agronomic parameters and phenolic composition of Vitis vinifera cv Tempranillo grapes.

BACKGROUND: The phenolic composition of grapes is key when making decisions about harvest date and ensuring the quality of grapes. The present study aimed to investigate the relationship between the detailed phenolic composition of grapes and the agronomic parameters and hyperspectral indices, with the latter being measured via field radiometry techniques. RESULTS: Good correlations were found between phenolic composition (both anthocyanin and flavanol composition) and some hyperspectral indices related to vigor, such as the NDVI (normalized difference vegetation index) and the SAVI (soil adjusted vegetation index). The strongest correlations were observed between the phenolic composition of grape skin at harvest time and variables measured from grapes at veraison time, as well as variables determined from grapevines at harvest time. The potential usefulness of these hyperspectral indices calculated from measurements performed directly on grapes or grapevines for estimating the anthocyanin and flavanol composition of grape skins was indicated by the high coefficients of determination (R2 = 0.7955 and R2 = 0.8594, respectively) as obtained by means of principal component regression. CONCLUSION: According to the results of the present study, hyperspectral indices calculated from measurements performed directly on grapes at veraison time or on grapevines at harvest time may be useful for estimating the anthocyanin and flavanol composition of grape skins. This suggests that field radiometry might provide valuable information for estimating the phenolic composition of grapes, which may prove to be very useful when establishing strategies for harvest planning. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice.

Fructose stimulates vasopressin in humans and can be generated endogenously by activation of the polyol pathway with hyperosmolarity. We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration. Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired. NEW & NOTEWORTHY: This study increases our understanding of the mechanisms leading to vasopressin release under conditions of water restriction (acute dehydration). Specifically, these studies suggest that the aldose reductase-fructokinase pathways may be involved in vasopressin synthesis in the hypothalamus and secretion by the pituitary in response to acute dehydration. Nevertheless, mice undergoing water restriction remain capable of maintaining sufficient vasopressin (copeptin) levels to allow normal urinary concentration. Further studies of the aldose reductase-fructokinase system in vasopressin regulation appear indicated.

Uric acid-dependent inhibition of AMP kinase induces hepatic glucose production in diabetes and starvation: evolutionary implications of the uricase loss in hominids.

Reduced AMP kinase (AMPK) activity has been shown to play a key deleterious role in increased hepatic gluconeogenesis in diabetes, but the mechanism whereby this occurs remains unclear. In this article, we document that another AMP-dependent enzyme, AMP deaminase (AMPD) is activated in the liver of diabetic mice, which parallels with a significant reduction in AMPK activity and a significant increase in intracellular glucose accumulation in human HepG2 cells. AMPD activation is induced by a reduction in intracellular phosphate levels, which is characteristic of insulin resistance and diabetic states. Increased gluconeogenesis is mediated by reduced TORC2 phosphorylation at Ser171 by AMPK in these cells, as well as by the up-regulation of the rate-limiting enzymes PEPCK and G6Pc. The mechanism whereby AMPD controls AMPK activation depends on the production of a specific AMP downstream metabolite through AMPD, uric acid. In this regard, humans have higher uric acid levels than most mammals due to a mutation in uricase, the enzyme involved in uric acid degradation in most mammals, that developed during a period of famine in Europe 1.5 × 10(7) yr ago. Here, working with resurrected ancestral uricases obtained from early hominids, we show that their expression on HepG2 cells is enough to blunt gluconeogenesis in parallel with an up-regulation of AMPK activity. These studies identify a key role AMPD and uric acid in mediating hepatic gluconeogenesis in the diabetic state, via a mechanism involving AMPK down-regulation and overexpression of PEPCK and G6Pc. The uricase mutation in the Miocene likely provided a survival advantage to help maintain glucose levels under conditions of near starvation, but today likely has a role in the pathogenesis of diabetes.

Synergistic effect of uricase blockade plus physiological amounts of fructose-glucose on glomerular hypertension and oxidative stress in rats.

Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders, and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n = 7/group) were studied during 8 wk: water + vehicle (V), water + oxonic acid (OA; 750 mg/k BW), sweetened beverage (SB; 11% fructose-glucose combination) + V, and SB + OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase, and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia, and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension, and SB alone induced insulin resistance. SB + OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic TG, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose.

In search of the perfect aphrodisiac: parallel use of bitter tonics in West Africa and the Caribbean.

ETHNOPHARMACOLOGICAL RELEVANCE: Enslaved Africans in the Americas had to reinvent their medicinal flora in an unknown environment by adhering to plants that came with them, learning from Amerindians and Europeans, using their Old World knowledge and trial and error to find substitutes for their homeland herbs. This process has left few written records, and little research has been done on transatlantic plant use. We used the composition of aphrodisiac mixtures across the black Atlantic to discuss the adaptation of herbal medicine by African diaspora in the New World. Since Africans are considered relatively recent migrants in America, their healing flora is often said to consist largely of pantropical and cultivated species, with few native trees. Therefore, we expected Caribbean recipes to be dominated by taxa that occur in both continents, poor in forest species and rich in weeds and domesticated exotics. MATERIALS AND METHODS: To test this hypothesis, we compared botanical ingredients of 35 African and 117 Caribbean mixtures, using Dentrended Correspondence Analysis, Cluster Analysis, Indicator Species Analysis and Mann-Whitney U tests. RESULTS: Very few of the 324 ingredients were used on both continents. A slightly higher overlap on generic and family level showed that Africans did search for taxa that were botanically related to African ones, but largely selected new, unrelated plants with similar taste, appearance or pharmacological properties. Recipes from the forested Guianas contained more New World, wild and forest species than those from deforested Caribbean islands. We recorded few 'transatlantic genera' and weeds never dominated the recipes, so we rejected our hypothesis. CONCLUSIONS: The popularity of bitter tonics in the Caribbean suggests an African heritage, but the inclusion of Neotropical species and vernacular names of plants and mixtures indicate Amerindian and European influence. We show that enslaved Africans have reinvented their herbal medicine wherever they were put to work, using the knowledge and flora that was available to them with great creativity and flexibility. Our analysis reveals how transplanted humans adapt their traditional medical practises in a new environment.

Recombinant human granulocyte-macrophage colony stimulating factor (sargramostim) as an alternative therapy for fistulizing Crohn's disease.

BACKGROUND: Impaired neutrophil function has been proposed in the pathogenesis of Inflammatory Bowel Disease. Failure to control the response to bacteria and bacterial products triggers the inflammatory cascade. Genetic disorders of neutrophil dysfunction exhibit gastrointestinal manifestations similar to Crohn's disease. Treatments that enhance neutrophil and macrophage function with colony-stimulating factors have been successful in these conditions. Some studies using sargramostin in patients with Crohn's disease have suggested a beneficial effect in disease activity, including fistulizing disease. The goal of the study was to evaluate the safety and efficacy of sargramostin in patients with fistulizing Crohn's disease who had not responded to conventional therapy or had developed adverse reaction to infliximab requiring discontinuation of the drug. METHODS: Patients with fistulizing Crohn's disease who had failed conventional therapy were recruited. Sargramostin 6 microg/kg subcutaneously daily for 8 weeks was prescribed. Follow-up included clinical evaluation, exam of the fistulas, laboratories, CDAI score, adverse events, compliance with therapy, quality of life assessment, and baseline and post-treatment abdomino-pelvic MRI. RESULTS: Three patients were enrolled. There were 4 perianal, 7 enterocutaneous and multiple enteroenteric fistulas. Two completed 8 weeks of treatment and 1 was discontinued at week 5 for a hypersensitivity reaction. Sargramostin was ineffective in all three. CONCLUSIONS: The small number of patients and the severity of their disease do not allow any conclusions about the drug effectiveness. Placebo-controlled studies, perhaps with less complicated patients, are needed to define a role, if any, of this therapy in fistulizing Crohn's disease.

New dammarane triterpenes from the aerial parts of Ibicella lutea grown in Argentina.

Two new dammarane triterpenes have been isolated from the aerial parts of Ibicella lutea, 3-acetyl-24-epi-polacandrin (1) and 1,3-diacetyl-24-epi-polacandrin (2), and were obtained along with the known compounds 20S,24S-epoxy-3beta,12beta,25-trihydroxydammarane (3) and apigenin. The structures of compounds 1 and 2 were deduced by spectroscopic studies and by chemical transformations leading to the preparation of derivatives 4-11. The structure and relative stereochemistry of 1 were verified by single-crystal X-ray analysis. The natural compounds and selected semisynthetic derivatives were evaluated against several tumor cells.

Evaluation of the effects of several zoanthamine-type alkaloids on the aggregation of human platelets.

Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the Zoanthus genus (Zoanthus nymphaeus and Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (11) and a synthetic derivative of norzoanthamine (16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure-activity relationships and suggest some mechanisms of action for this type of compounds.