Antimicrobial and anti-inflammatory activities, wound-healing effectiveness and chemical characterization of the latex of Jatropha neopauciflora Pax.

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha neopauciflora Pax is an endemic species to Mexico, and its latex is used in traditional medicine to treat mouth infections when there are loose teeth and to heal wounds. In this research, we evaluated the antimicrobial activity, wound healing efficacy and chemical characterization of J. neopauciflora latex in a murine model. MATERIALS AND METHODS: The antibacterial activity was determined using Gram positive and negative strains, the antifungal activity was determined using yeast and filamentous fungi, and the wound healing efficacy of the latex was determined using the tensiometric method. The anti-inflammatory activity was evaluated using the plantar oedema model in rats, administering the latex orally and topically. Cytotoxic activity was determined in vitro in two different cell lines. Antioxidant capacity, total phenolics, total flavonoids, reducing carbohydrates and latex proteins were quantified. The latex analysis was performed by High Performance Liquid Chromatography (HPLC). Finally, molecular exclusion chromatography was performed. RESULTS: The latex demonstrated antibacterial activity. The most sensitive strains were Gram positive bacteria, particularly S. aureus (MIC=2mg/mL), and the latex had bacteriostatic activity. The latex did not show antifungal activity. The latex demonstrated a wound-healing efficacy, even the positive control (Recoveron). The orally administered latex demonstrated the best anti-inflammatory activity and was not toxic to either of the 2 cell lines. The latex had a high antioxidant capacity (SA50=5.4µg/mL), directly related to the total phenolic (6.9mg GAE/mL) and flavonoid (12.53µg QE/mL) concentration. The carbohydrate concentration was 18.52µg/mL, and fructose was the most abundantly expressed carbohydrate in the latex (14.63µg/mL, 79.03%). Additionally, the latex contained proteins (7.62µg/mL) in its chemical constitution. As secondary metabolites, the HPLC analysis indicated the presence of phenols and flavonoids. CONCLUSIONS: The J. neopauciflora latex promotes the wound healing process by avoiding microorganism infections, inhibiting inflammation and acting as an antioxidant.

BIOLOGICAL PROPERTIES AND CHEMICAL COMPOSITION OF JATROPHA NEOPAUCIFLORA PAX.

BACKGROUND: Ethnopharmacological relevance. Jatropha neopauciflora (Pax) is an endemic species of the Tehuacan- Cuicatlan Valley, Mexico. This species has long been used as a remedy to alleviate illnesses of bacterial, fungal and viral origin. Aim of the study. Experimentally test the traditional use of Jatropha neopauciflora in Mexican traditional medicine. MATERIALS AND METHODS: The methanol extract (MeOH1), of Jatropha neopauciflora (Euphorbiaceae) was obtained by maceration. Next, the methanol (MeOH2) and hexane (H) fractions were obtained. The essential oil was obtained by hydro- distillation. The extract, fractions and essential oil were analyzed by GC-MS. The antimicrobial activity was measured by the disc diffusion agar and radial inhibition growth methods. RESULTS: The extract and fractions showed antibacterial activity against eleven strains (five Gram-positive and six Gram- negative) and a bacteriostatic effect in the survival curves for Staphylococcus aureus and Vibrio cholerae. The extract and fractions were also shown to have antifungal activity, particularly against Trichophyton mentagrophytes (CF50 = MeOH1: 1.07 mg/mL, MeOH2: 1.32 mg/mL and H: 1.08 mg/mL). The antioxidant activity of MeOH1 (68.6 µg/mL) was higher than for MeOH2 (108.1 µg/mL). The main compounds of the essential oil were ß-pinene, 1,3,8-p-menthatriene, ledene, m- menthane, linalyl acetate and 3-carene. The main compounds of MeOH1 were ß-sitosterol, lupeol and pyrogallol; the main compounds of MeOH2 were ß-sitosterol, spathulenol, coniferyl alcohol and lupeol; and the main compounds of H were ß-sitostenone, γ-sitosterol and stigmasterol. CONCLUSIONS: This study indicates that Jatropha neopauciflora is a potential antibacterial and antifungal agent.

The effect of leptin replacement on sleep-disordered breathing in the leptin-deficient ob/ob mouse.

Obese leptin-deficient (ob/ob) mice demonstrate defects in upper airway structural and neuromuscular control. We hypothesized that these defects predispose to upper airway obstruction during sleep, and improve with leptin administration. High-fidelity polysomnographic recordings were conducted to characterize sleep and breathing patterns in conscious, unrestrained ob/ob mice (23 wk, 67.2 ± 4.1 g, n = 13). In a parallel-arm crossover study, we compared responses to subcutaneous leptin (1 µg/h) vs. vehicle on respiratory parameters during NREM and REM sleep. Upper airway obstruction was defined by the presence of inspiratory airflow limitation (IFL), as characterized by an early inspiratory plateau in airflow at a maximum level (V̇Imax) with increasing effort. The severity of upper airway obstruction (V̇Imax) was assessed along with minute ventilation (V̇E), tidal volume (VT), respiratory rate (RR), inspiratory duty cycle, and mean inspiratory flow at each time point. IFL occurred more frequently in REM sleep (37.6 ± 0.2% vs. 1.1 ± 0.0% in NREM sleep, P < 0.001), and leptin did not alter its frequency. V̇Imax (3.7 ± 1.1 vs. 2.7 ± 0.8 ml/s, P < 0.001) and V̇E increased (55.4 ± 22.0 vs. 39.8 ± 16.4 ml/min, P < 0.001) with leptin vs. vehicle administration. The increase in V̇E was due to a significant increase in VT (0.20 ± 0.06 vs. 0.16 ± 0.05 ml, P < 0.01) rather than RR. Increases in V̇E were attributable to increases in mean inspiratory flow (2.5 ± 0.8 vs. 1.8 ± 0.6 ml/s, P < 0.001) rather than inspiratory duty cycle. Similar increases in V̇E and its components were observed in non-flow-limited breaths during NREM and REM sleep. These responses suggest that leptin stabilized pharyngeal patency and increased drive to both the upper airway and diaphragm during sleep.

Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases. / Mecanismos epigenéticos en el desarrollo de la memoria y su implicación en algunas enfermedades neurológicas.

INTRODUCTION: Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. DEVELOPMENT: This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. CONCLUSIONS: The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases.

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse.

Sleep is associated with marked alterations in ventilatory control that lead to perturbations in respiratory timing, breathing pattern, ventilation, pharyngeal collapsibility, and sleep-related breathing disorders (SRBD). Mouse models offer powerful insight into the pathogenesis of SRBD; however, methods for obtaining the full complement of continuous, high-fidelity respiratory, electroencephalographic (EEG), and electromyographic (EMG) signals in unrestrained mice during sleep and wake have not been developed. We adapted whole body plethysmography to record EEG, EMG, and respiratory signals continuously in unrestrained, unanesthetized mice. Whole body plethysmography tidal volume and airflow signals and a novel noninvasive surrogate for respiratory effort (respiratory movement signal) were validated against simultaneously measured gold standard signals. Compared with the gold standard, we validated 1) tidal volume (correlation, R(2) = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2) inspiratory airflow (correlation, R(2) = 0.92, P < 0.001; agreement within 4%, P < 0.001); 3) expiratory airflow (correlation, R(2) = 0.83, P < 0.001); and 4) respiratory movement signal (correlation, R(2) = 0.79-0.84, P < 0.001). The expiratory airflow signal, however, demonstrated a decrease in amplitude compared with the gold standard. Integrating respiratory and EEG/EMG signals, we fully characterized sleep and breathing patterns in conscious, unrestrained mice and demonstrated inspiratory flow limitation in a New Zealand Obese mouse. Our approach will facilitate studies of SRBD mechanisms in inbred mouse strains and offer a powerful platform to investigate the effects of environmental and pharmacological exposures on breathing disturbances during sleep and wakefulness.

[Diseases caused by triplet expansion]. / Enfermedades causadas por expansión de tripletes.

INTRODUCTION: Today we know of a group of mutations caused by the expansion of nucleotide triplets, which are very unstable in meiosis and mitosis. Four types of triplets have the capacity for pathogenic expansion in human beings (CGG/ GCC, CAG/GTC, CTG/GAC and GAA/CTT) and maybe located both in coding sequences (bulbospinal muscular atrophy, Huntington's disease and certain spinocerebellar ataxias) and non-coding sequences (fragile X syndrome, Friedreich's ataxia, myotonic dystrophy). Trinucleotide expansion may lead to gains or losses in gene functioning and seems to be associated to a variety of factors, some of which are directly related with the expansive process (cis-acting) and others whose interaction with the triplets helps to make them increasingly more unstable (trans-acting). Medium-sized expansions (pre-mutations), although clinically silent, do show a marked tendency to expand into complete mutations during the transition along the germinal line. The models that have been proposed to explain triplet expansion involve gene recombination and replication processes; however, they have not fully succeeded in explaining the phenomena related to mutation or phenotypic expression in these diseases. DEVELOPMENT: This work examines the most recent concepts related to the dynamic mutation processes that give rise to human diseases; it also reviews the most important clinico-biological aspects observed in those diseases. CONCLUSIONS: Dynamic mutation processes represent a new concept in the molecular biology of gene mutations. An ever increasing number of pathologies are caused by this type of DNA alterations, which, as a whole, display very interesting clinico-biological characteristics.

Derrame pleural fetal. Etiología, manejo y pronóstico / Fetal pleural effusion. Etiology, management and prognosis)

Introducción. El derrame pleural fetal (DPF) es una entidad rara que puede amenazar la viabilidad fetal. El objetivo es revisar el DPF analizando su etiología, manejo y pronóstico.Métodos. Estudio retrospectivo de 16 casos de DPF de16.971 partos (0,094%) realizados en el Hospital Maternal La Fe en el período 2003-2006. Se valora la etiología, manejo, uso de técnicas invasivas, forma de parto y evolución neonatal.Resultados. La edad gestacional media del diagnósticofue 25±1 semanas (14-38), y la de finalización del embarazo fue 28±1 semanas (rango: 16-39). El DPF asoció hidrops en 8 casos (50%), ascitis en 14 casos (87,5%), cardiopatías 5 casos (31,25 %) y polihidramnios en 6 casos (37,5 %). La amniocentesis demostró aneuploidía en 3 casos (18,75%). El sexo fue varón en 12 casos, hembra en 3 y ambiguo en 1 (p<0,05). De las 16 gestaciones: 2 fueron abortos tardíos y 2 interrupciones voluntarias del embarazo (IVE). Sólo en 12 casos se controló la gestación, desapareciendo el DPF en 3 casos (25%). La finalización de la gestación fue: 7 cesáreas(58 %), y 5 partos vaginales (42 %). Solo en 5 casos (41%) hubo recién nacidos vivos, los 3 casos de desaparición y 2 casos sin desaparición. La tasa de mortalidad durante el embarazo fue del 58,3% y perinatal del 66,6%.Conclusiones. El derrame pleural fetal se asocia a unaalta morbimortalidad perinatal, siendo más frecuente en varones. Son factores de buen pronóstico la reabsorción durante la gestación y la finalización tardía

Introduction. Fetal pleural effusion (FPE) is an uncommoncondition that is life-threatening to the fetalviability. This study has aimed to review FPE, analyzingetiology, management and prognosis.Methods. Retrospective study (2003-2006) of 16 FPEfrom among 16,971 deliveries (0.094%) performed in theMaternity Hospital La Fe. Etiology, management, use ofinvasive techniques, delivery method and neonatal outcomewere studied.Results. Mean gestational age at diagnosis was 25±1(14-38) weeks, and gestational age at delivery was 28±1(16-39) weeks. FPE was associated to hydrops in 8 cases(50 %), ascitis 14 cases (87.5 %), heart disease 5 cases(31.25%), polyhydramnias 6 cases (37.5%). The amniocentesis showed aneuploidy in 3 cases (18.75%). Gender was male in 12 case, female in 3 and ambiguous in one (p<0.05). Among 16 pregnancies, 2 were late miscarriages and 2 Voluntary Termination of Pregnancy. The pregnancies were controlled in only 12 cases, the FPE disappearing in 3 cases (25%). The end of the pregnancy was by cesarean section in 7 (58%) and vaginal deliveries in 5 (42%). There were live newborns in only 5 cases (41%) (5/12), 3 cases of disappearance and 2 without disappearance. Mortality rate in pregnancy was 58.3% and perinatal mortality rate was 66.6%.Conclusions. Fetal pleural effusion is associated to ahigh perinatal morbidity-mortality, this being more frequent in males. Good prognostic factors are reabsorption during pregnancy of late birth

Menstrual patterns and progesterone circulating levels following different procedures of tubal occlusion.

This study was undertaken to assess the effects of different tubal occlusion procedures on ovarian function. Three groups of subjects randomized to tubal occlusion by laparoscopy and Yoon ring (24 subjects), minilaparotomy and Yoon ring (19 subjects) and minilaparotomy and Pomeroy (22 subjects), and one separate control group of 26 healthy subjects not using any form of contraception were studied in a prospective design. The characteristics of the menstrual patterns were studied for one year after sterilization. Determination of the circulating progesterone levels were made on days 15, 20 and 25 of menstrual cycles initiated 1, 3, 6 and 12 months following the tubal ligation. In the analysis of the bleeding pattern there was a statistically significant difference in the mean segment length and in the longest bleeding-free interval in the subjects who had been sterilized by minilaparotomy with Yoon ring, when compared to the other two study groups and to the control group. However, the magnitude of this difference in number of days was not considered clinically significant. There was no statistically significant difference in the percentage of ovulatory cycles within the study and the control groups, or when the results of the study groups were compared with each other or to the control group.

PIP: This study was undertake to assess the effects of different tubal occlusion procedures on ovarian function. 3 groups of subjects randomized to tubal occlusion by laparoscopy and Yoon ring (24 subjects), minilaparotomy and Yoon ring (19 subjects) and minilaparotomy and Pomeroy (22 subjects), and 1 separate control group of 26 healthy subjects not using any form of contraception were studied in a prospective design. The characteristics of the menstrual patterns were studied for 1 year after sterilization. Determination of the circulating progesterone levels were made on days 15, 20, and 25 of menstrual cycles initiated 1,3,6 and 12 months following the tubal ligation. In the analysis of the bleeding pattern there was a statistically significant difference in the mean segment length and in the longest bleeding-free interval in the subjects who had been sterilized by minilaparotomy with Yoon ring, when compared to the other 2 study groups and to the control group. However, the magnitude of this difference in number of days was not considered clinically significant. There was no statistically significant difference in the % of ovulatory cycles within the study and the control groups, or when the results of the study groups were compared with each other or to the control group. (Author's).

Sustained intrauterine release of AMCA to reduce menstrual blood loss.

PIP: Increased menstrual blood loss (MBL) is 1 of the side effects associated with IUDs. Attempts at reducing the increase in MBL have included the use of horomones, such as progesterone and levonorgestrel, and antifibrinolytic agents, such as tranexamic acid (AMCA) and aminiocaproic acid (EACA). This paper presents the results of a randomly allocated comparative study of menstrual pattern changes with a Lippes loop D (LLD) modfied to slowly release AMCA and a control LLD that released no AMCA. Quantitative MBL data were collected at a preinsertion cycle and at follow-up vistits scheduled 1, 2, 3, and 6months postinsertion for 11 control LLD cases and 10 cases assigned an AMCA-loaded LLD. The increase in MBL over preinsertion levels was significantly less with the AMCA device. The mean increase in MBL after the 1st cycle was 45.3 ml among control LLD acceptors compared to 16.0 ml among AMCA LLD users. These differences persisted through the 1st 3 postinsertion cycles, but disappeared by the 6th month. AMCA was effective in reducing the initial increase in MBL and other menstrual aside effects that occur with IUD insertion, but its effectiveness is limited by the amount of AMCA which can be loaded into the device.^ieng