Bioactivity And Dereplication Of Phenolic Compounds In Medicinal Plants

Three medicinal plants with recognized anti-inflammatory potential, identified as “erva de São João“ (Ageratum conyzoides), “Tanchagem“ (Plantago major) and “ Bardana“ (Arctium lappa L.) were obtained from a medicinal herbs company located in Teófilo Otoni city (Minas Gerais State, Brazil). The dry plant material obtained in packages was submitted to the chemical procedures to prepare the crude extracts by maceration according to the Brazilian pharmacopoeia legislation. After extraction, the samples were subjected to 1H NMR, TLC and Capillary Electrophoresis analysis by co-injection of authentic patterns of phenolic acids and flavonoids to identify the major compounds and classes of secondary metabolites present in each material and then their chemical and biological potential was assessed by DPPH free radical inhibition assay and antimicrobial against E. coli. The results obtained allow us to conclude that the phytopreparation was effective in the extraction of compounds with antioxidant potential and the three species presented a high concentration of flavonoids and other phenolics that is compatible with the chemosystematic data. The screening obtained by 1H NMR spectroscopy, TLC and Capillary Electrophoresis with ultraviolet detection analysis provided us a qualitative profile of the phytochemicals present in each material. None of the extracts were active against Escherichia coli by antibacterial disk diffusion assay at concentration of 1 mg/ml.

CRISPR/Cas9: reflexiones bioéticas sobre las modificacion es genómicas / CRISPR/Cas9: bioethical reflections on genome modifications

CRISPR/Cas9 puede ser considerado el descubrimiento biotecnológico del siglo. Sin embargo, las reflexiones sobre la aceptabilidad y factibilidad de producir cambios permanentes en el ADN de gametos y embriones, ha arrojado nueva luz sobre CRISPR. Por ejemplo al notar que las alteraciones en la línea germinal, pueden ser heredadas y por lo tanto observarse a lo largo de las generaciones. Aunque inicialmente estas transformaciones puedan ser deseables, más allá del impacto tecnológico, la tecnología CRISPR parece tener varias implicancias éticas para la sociedad. Estas pueden ser analizadas a partir de las distintas reacciones que ha despertado CRISPR en todo el mundo. Por ejemplo, en el pedido de suspensión total de la aplicación clínica (es decir, la prohibición de transferir en el útero un embrión previamente modificado con la tecnología CRISPR) hasta tanto no se hayan alcanzado y aprobado ciertos requisitos indispensables para la investigación clínica. En general, esta tecnología ha sido prematuramente caracterizada como "disruptiva". Este texto analizará las implicancias éticas, políticas, sociales, médicas y subjetivas a la luz del fenómeno social - no tecnológico - creado por CRISPR.

CRISPR/Cas9 can be considered the biotechnogical discovery of the century. However, reflections on the plausibility and feasibility of producing permanent changes in the DNA of gametes and embryos throw new light on CRISPR. As in modifications in the germinal line can be inherited and hence, observed throughout generations. While this might be desirable for some, besides the technological impact, CRISPR also seems to have an ethical impact on society. These ethical impacts can be observed in the diverse reactions to CRISPR from across the globe. For instance, a request for the complete suspension of clinical application (that is, the prohibition of implanting an embryo with CRISPR modifications in the uterus) till certain basic research requirements were met and approved. Broadly, this technology has been prematurely also characterized as "disruptive" by some. This paper will analyze these ethical, political, social, medical and subjective reactions in light of the social - not technological - phenomenon created by CRISPR.

Cocos nucifera (L.) (Arecaceae): A phytochemical and pharmacological review

Cocos nucifera (L.) (Arecaceae) is commonly called the “coconut tree” and is the most naturally widespread fruit plant on Earth. Throughout history, humans have used medicinal plants therapeutically, and minerals, plants, and animals have traditionally been the main sources of drugs. The constituents of C. nucifera have some biological effects, such as antihelminthic, anti-inflammatory, antinociceptive, antioxidant, antifungal, antimicrobial, and antitumor activities. Our objective in the present study was to review the phytochemical profile, pharmacological activities, and toxicology of C. nucifera to guide future preclinical and clinical studies using this plant. This systematic review consisted of searches performed using scientific databases such as Scopus, Science Direct, PubMed, SciVerse, and Scientific Electronic Library Online. Some uses of the plant were partially confirmed by previous studies demonstrating analgesic, antiarthritic, antibacterial, antipyretic, antihelminthic, antidiarrheal, and hypoglycemic activities. In addition, other properties such as antihypertensive, anti-inflammatory, antimicrobial, antioxidant, cardioprotective, antiseizure, cytotoxicity, hepatoprotective, vasodilation, nephroprotective, and anti-osteoporosis effects were also reported. Because each part of C. nucifera has different constituents, the pharmacological effects of the plant vary according to the part of the plant evaluated.

Association between the increase in brain temperature and physical performance at different exercise intensities and protocols in a temperate environment

There is evidence that brain temperature (Tbrain) provides a more sensitive index than other core body temperatures in determining physical performance. However, no study has addressed whether the association between performance and increases in Tbrain in a temperate environment is dependent upon exercise intensity, and this was the primary aim of the present study. Adult male Wistar rats were subjected to constant exercise at three different speeds (18, 21, and 24 m/min) until the onset of volitional fatigue. Tbrain was continuously measured by a thermistor inserted through a brain guide cannula. Exercise induced a speed-dependent increase in Tbrain, with the fastest speed associated with a higher rate of Tbrain increase. Rats subjected to constant exercise had similar Tbrain values at the time of fatigue, although a pronounced individual variability was observed (38.7-41.7°C). There were negative correlations between the rate of Tbrain increase and performance for all speeds that were studied. These results indicate that performance during constant exercise is negatively associated with the increase in Tbrain, particularly with its rate of increase. We then investigated how an incremental-speed protocol affected the association between the increase in Tbrain and performance. At volitional fatigue, Tbrain was lower during incremental exercise compared with the Tbrain resulting from constant exercise (39.3±0.3 vs 40.3±0.1°C; P<0.05), and no association between the rate of Tbrain increase and performance was observed. These findings suggest that the influence of Tbrain on performance under temperate conditions is dependent on exercise protocol.

Monoterapia biológica en pacientes con artritis reumatoidea en Argentina / Biological monotherapy in patients with rheumatoid arthritis in Argentina

Introducción: La utilización de agentes biológicos para el tratamiento de la Artritis Reumatoidea (AR) es habitualmente usada en aquellos pacientes con enfermedad activa que no hayan respondido al tratamiento con drogas modificadoras de la Artritis Reumatoidea convencionales (DMARD, por sus siglas en inglés) o que hayan presentado intolerancia a las mismas. Al estado actual de la evidencia, la terapia combinada de agentes biológicos más un DMARD convencional (principalmente metotrexato) constituye el estándar de tratamiento. Sin embargo existen algunos escenarios como la intolerancia, la falta de adherencia y la aparición de eventos adversos a las DMARDs convencionales donde la monoterapia biológica emerge como una opción terapéutica válida. Según los distintos registros a nivel internacional, la frecuencia de utilización de agentes biológicos en monoterapia oscila entre 12 a 39%. Debido a la ausencia de estos datos a nivel local decidimos realizar este estudio para conocer el porcentaje de pacientes que se encuentran en monoterapia biológica y analizar las causas que llevaron a este tipo de tratamiento. Materiales y métodos: Estudio de tipo corte transversal donde se invitó a participar a diferentes centros reumatológicos distribuidos a lo largo de Argentina. Cada centro revisó las historias clínicas de los últimos 30 a 50 pacientes consecutivos vistos con AR, mayores de 18 años, que habían presentado inadecuada respuesta al tratamiento con DMARDs y que estaban bajo tratamiento biológico. Se completaba una ficha por cada paciente incluido, registrando datos demográficos, de la enfermedad y tratamientos previos. Resultados: Se incluyeron 32 centros y se evaluaron 1148 historias clínicas de pacientes con AR durante el mes de octubre y noviembre del 2012. Un 21,4% (246) de los pacientes al momento del estudio se encontraba bajo tratamiento biológico en monoterapia...

Introduction: The use of biological agents for the treatment of rheumatoid arthritis (RA) is commonly used in patients with active disease who have not responded to treatment with conventional rheumatoid arthritis-modifying drugs (DMARDs) or Who have presented intolerance to them. At the present state of evidence, combined therapy of biological agents plus conventional DMARD (mainly methotrexate) is the standard of treatment. However, there are some scenarios such as intolerance, lack of adherence and the appearance of adverse events to conventional DMARDs where biological monotherapy emerges as a valid therapeutic option. According to different international registries, the frequency of use of biological agents in monotherapy ranges from 12 to 39%. Due to the absence of these data at the local level we decided to carry out this study to know the percentage of patients who are in biological monotherapy and to analyze the causes that led to this type of treatment. Materials and methods: A cross-sectional study where different rheumatologic centers throughout Argentina were invited to participate. Each center reviewed the medical records of the last 30 to 50 consecutive patients seen with RA, older than 18 years, who had inadequate response to treatment with DMARDs and who were under biological treatment. One card was completed for each patient included, recording demographic, disease and previous treatment data. Results: Thirty-two centers were included and 1148 clinical records of patients with RA were evaluated during October and November 2012. A total of 244 patients (246) at the time of the study were under monotherapy...

Effects of resistance exercise on ascendent aorta on ovariectomized elderly rats

Studies have shown a strong relationship between menopause, diet, physical inactivity and presence of risk factors causing endothelial and tissue damages, leading to increased risk of developing cardiovascular disease. The aim of this study was to investigate the influence of resistance training on the effects of estrogen deprivation in aortic collagen and elastic tissue in aging. Fifteen Wistar female rats, 4 months-old, average weight 240 g were studied. All animals were ovariectomized at 6 months of age, after divided into 3 groups (n = 5): Sedentary adult (13 months), Sedentary old and Trained old (both with 17 months). All animals were ovariectomized at 6 months of age. The animals were observed for 8 months after its ovariectomy and then submitted to resistance training protocol during 12 weeks. At the end of the experiment the animals were euthanized. Samples of the ascending aorta were sectioned, fixed, processed and stained for examination by light microscopy. Photomicrographs were used for stereological study and analyzed the following parameters: body weight, volume density of collagen fibers and elastic lamellae. No significant difference was found between the initial and final weights in the studied groups. Resistance training attenuates the increase in volume density of elastic lamellae (21%) and collagen fibers (16%), when compared with the sedentary older group.

Influence of resistance training in left ventricle of ovariectomized elderly rats

Several cardiovascular changes evoked by aging affect negatively the quality of people’s lives, among them is the reduced functional capacity. Menopausal women, affected by the suspension of the ovarian hormones, suffer more intensely from metabolic and cardiovascular changes. It is known that physical training causesbiochemical, electrical, morphological, and mechanical adaptations in the cardiac muscle, which togetherprovide an improvement in the cardiac function. The goal of the present study was to evaluate theeffect of resistance training in the left ventricle of ovariectomized rats through stereological analysis. Westudied  15  Wistar female rats, 4 months- old, average weight 240 g. All animals were ovariectomized at9 months of age and then divided into 3 groups of five individuals as follows: Ovariectomized Sedentary Adult(13 months) (OSA), Ovariectomized Sedentary Elderly (17 months) (OSE), and Ovariectomized TrainedElderly (17 months) (OTE). The rats were monitored for 13 months and subsequently underwent resistancetraining for 12 weeks. The stereological analysis was performed using light microscopy techniques and dataobtained for each group were tabulated and statistically compared using ANOVA and post hoc Tukey tests(p ≤ 0.05). It was verified that training decreased volume density of myocyte, interstitium and collagen fibersfollowed by increased volume density of capillaries, when compared with the ovariectomized sedentary elderly(OSE). Our data suggest that resistance training minimizes changes in the myocardium of elderly rats deprivedof ovarian hormones.

Effects of aerobic exercise on soleus muscle of rats with metabolic syndrome

Introduction: Studies have shown a strong relationship between physical activity and the presence of cardiovascular risk factors such as hypertension, insulin resistance, diabetes, dyslipidemia and obesity that characterize the metabolic syndrome. Moreover, the practice of regular physical activity has been recommended for the prevention and treatment of this syndrome. Objectives: The aim of this study was to analyze by histomorphometric techniques, the effect of aerobic exercise in the soleus muscle of rats with metabolic syndrome. Methodology: A total of 15 male Wistar rats, 150 days old, divided into three groups (n = 5): sedentary, control (C); metabolic syndrome (MS) and trained, metabolic syndrome (TMS). The induction of MS was performed using fructose in the drinking water of animals. From the 9th week of induction, animals in the Training groups underwent exercise treadmill belt (Imbramed TK-01) with moderate intensity (50-70% of maximum speed achieved in the stress test). Physical training was conducted for nine weeks, with a frequency of 5 times per week, for about 60 minutes. The procedures were approved by the Ethics Committee of the São Judas Tadeu University (protocol Nr 060/2007). At the end of the experiment the animals were euthanized by decapitation. The right soleus muscle was sectioned, fixed and treated for conducting conventional histology, and the slides stained by HE and Picrosirius methods. Photomicrographs of 10 fields per animal were captured by light microscope, transferred to the image analysis program (Software Axio Vision, Zeiss). We measured the cross-sectional areas of muscle fibers and to analyze the volume densities of muscle fibers, capillaries, and interstitial collagen fibers, was used stereological method (252 points). The statistical analysis used was ANOVA One Way and Tukey test (p < 0.05)...

Salt and insulin sensitivity after short and prolonged high salt intake in elderly subjects

Salt sensitivity and insulin resistance are correlated with higher cardiovascular risk. There is no information about changes in salt sensitivity (SS) and insulin sensitivity (IS) after a chronic salt overload in humans. The aim of this study was to evaluate these parameters in the elderly. Seventeen volunteers aged 70.5 ± 5.9 years followed a low-salt diet (LSD) for 1 week and a high-salt diet (HSD) for 13 weeks. We evaluated SS after one week (HSD1) and after 13 weeks (HSD13), and subjects’ IS and lipids on their usual diet (UD) at HSD1, and at HSD13. Blood pressure (BP) was measured at each visit and ambulatory blood pressure monitoring (ABPM) was performed twice. SS was the same at HSD1 and HSD13. Systolic BP was lower on LSD than on UD (P = 0.01), HSD1 (P < 0.01) and HSD13 (P < 0.01). When systolic and diastolic BP were evaluated by ABPM, they were higher at HSD13 during the 24-h period (P = 0.03 and P < 0.01) and during the wakefulness period (P = 0.02 and P < 0.01) compared to the UD. Total cholesterol was higher (P = 0.04) at HSD13 than at HSD1. Glucose and homeostasis model assessment (HOMA) were lower at HSD1 (P = 0.02 and P = 0.01) than at HSD13. Concluding, the extension of HSD did not change the SS in an elderly group. The higher IS found at HSD1 did not persist after a longer HSD. A chronic HSD increased BP as assessed by ABPM.

Comparison of sweat rate during graded exercise and the local rate induced by pilocarpine

Centrally stimulated sweat rate produced by graded exercise until exhaustion was compared to the local sweat rate induced by pilocarpine, often used as a sweating index for healthy individuals. Nine young male volunteers (22 ± 4 years) were studied in temperate environment in two situations: at rest and during progressive exercise with 25 W increases every 2 min until exhaustion, on a cycle ergometer. In both situations, sweating was induced on the right forearm with 5 ml 0.5 percent pilocarpine hydrochloride applied by iontophoresis (1.5 mA, 5 min), with left forearm used as control. Local sweat rate was measured for 15 min at rest. During exercise, whole-body sweat rate was calculated from the body weight variation. Local sweat rate was measured from the time when heart rate reached 150 bpm until exhaustion and was collected using absorbent filter paper. Pharmacologically induced local sweat rate at rest (0.4 ± 0.2 mg cm-2 min-1) and mean exercise-induced whole-body sweat rate (0.4 ± 0.1 mg cm-2 min-1) were the same (P > 0.05) but were about five times smaller than local exercise-induced sweat rate (control = 2.1 ± 1.4; pilocarpine = 2.7 ± 1.2 mg cm-2 min-1), indicating different sudorific mechanisms. Both exercise-induced whole-body sweat rate (P < 0.05) and local sweat rate (P < 0.05) on control forearm correlated positively with pilocarpine-induced local sweat rate at rest. Assuming that exercise-induced sweating was a result of integrated physiological mechanisms, we suggest that local and whole-body sweat rate measured during graded exercise could be a better sweating index than pilocarpine.

Heat storage rate and acute fatigue in rats

Thermal environmental stress can anticipate acute fatigue during exercise at a fixed intensity ( percentVO2max). Controversy exists about whether this anticipation is caused by the absolute internal temperature (Tint, ºC), by the heat storage rate (HSR, cal/min) or by both mechanisms. The aim of the present study was to study acute fatigue (total exercise time, TET) during thermal stress by determining Tint and HSR from abdominal temperature. Thermal environmental stress was controlled in an environmental chamber and determined as wet bulb globe temperature (ºC), with three environmental temperatures being studied: cold (18ºC), thermoneutral (23.1ºC) or hot (29.4ºC). Six untrained male Wistar rats weighing 260-360 g were used. The animals were submitted to exercise at the same time of day in the three environments and at two treadmill velocities (21 and 24 m/min) until exhaustion. After implantation of a temperature sensor and treadmill adaptation, the animals were submitted to a Latin square experimental design using a 2 x 3 factorial scheme (velocity and environment), with the level of significance set at P<0.05. The results showed that the higher the velocity and the ambient temperature, the lower was the TET, with these two factors being independent. This result indicated that fatigue was independently affected by both the increase in exercise intensity and the thermal environmental stress. Fatigue developed at different Tint and HSR showed the best inverse relationship with TET. We conclude that HSR was the main anticipating factor of fatigue

Dietary sodium intake and cardiac nerve cell hypertrophy in Wistar rats

We determined the effect of dietary sodium intake (0.15 and 8 per cent NACl) on the cardiac neuron size of normotensive 3-week old Wistar rats. An increase in dietary sodium for 48 weeks induced an increase in neuronal size. The number of large neurons (larger than 500 muM2) increased significantly (chi-square test) in rats ingesting 8 per cent NaCl in their food. The rats presented hypertension (128 ñ 9 vs 134 ñ 16 mmHg; difference not significant, Student t-test) and a statistically significant increase in cardiac muscle mass (1.6 ñ 0.1 vs 2.0 ñ 0.2 mg/g of rat). We conclude that food sodium can significantly increase cardiac nerve cell size and this trophic response occurs concomitantly with an increase of cardiac muscle mass.