Background Subjective cognitive function is an important outcome measure in oncology. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a quality of life (QoL) measure that includes indices of physical, emotional, social, and neurologic aspects of disease but does not measure cognitive function. This study seeks to validate a novel index of cognition derived from the FACT-Br. Methods Patients with heterogeneous cancer diagnoses (N = 214) completed neuropsychological evaluation and self-report measures. Nine FACT-Br items regarding cognition were combined to form the FACT-Br-cognitive index (CI). Reliability was evaluated by exploratory factor analysis and internal consistency. Concurrent validity was assessed by correlating FACT-Br-CI with the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive-8 scales. Discriminant validity was assessed by correlating FACT-Br-CI with other FACT-Br indices and the Beck Depression and Anxiety Inventories (BDI, BAI). Exploratory analyses evaluated the impact of cognitive performance and disease variables on FACT-Br-CI. Results The FACT-Br-CI consisted of a single factor that demonstrated high internal consistency (α = 0.867) and strong concurrent validity, correlating strongly with PROMIS Cognitive-8 scales (r = 0.675-0.782). The relationship between the FACT-Br-CI and other FACT subscales ranged from moderate to strong (r = 0.372-0.601), as did correlations with measures of depression (BDI, r = -0.621) and anxiety (BAI, r = -0.450). Modest correlations were observed with neuropsychological measures (rs = 0.249-0.300). Conclusions The FACT-Br-CI is a reliable and valid measure of self-reported cognition. Studies that included the FACT-Br could be retrospectively analyzed to assess subjective cognitive outcomes, enriching the information from prior research. Integration of the FACT-Br-CI in routine clinical care may be an efficient method of monitoring cognition.

Abstract INTRODUCTION Subjective cognitive dysfunction is an important outcome measure in neuro-oncology and may provide additional information beyond performance-based neuropsychological testing. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a frequently used quality of life (QoL) measure that includes indices of physical, emotional, social, and neurologic aspects of disease, but does not measure cognitive concerns. This study seeks to develop and validate an index of self-reported cognition derived from existing items on the FACT-Br. METHODS 145 patients (Mage=51.08, Medu=15.63) with heterogeneous brain tumor diagnoses completed neuropsychological evaluation including cognitive testing and self-report measures. Nine FACT-Br items regarding cognition were combined to form the Cognitive Index (CI). Reliability of the CI was measured with Cronbach’s alpha. Concurrent validity was assessed by correlating the CI with the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Abilities-8 or PROMIS Cognitive Concerns-8. Discriminant validity was assessed by correlation of the CI with other FACT-Br indices and the Beck Depression and Anxiety Inventories (BDI, BAI). RESULTS Internal consistency within the CI was high (Cronbach’s a 0.864). The CI correlated strongly with the PROMIS-Abilities (r =.680; p< 0.001) and PROMIS-Concerns (r=.780; p< 0.001) indicating high convergent validity. Moderate correlations were observed between the CI and the physical and functional subscales of the FACT (r=.453 and .555), whereas correlations with the social and emotional functioning subscales were weaker (r=.381 and .325). The FACT-Br-CI correlated strongly with BDI (r=-.622) and more weakly with the BAI (r=-.344). Consistent with prior literature, the CI showed modest correlations with neuropsychological measures, including verbal memory encoding (r=.300), verbal fluency (r=.252) and a composite measure of cognition (r=.249; all p’s< .01). CONCLUSIONS The FACT-Br-CI is a reliable and valid measure of self-reported cognition. Studies that include the FACT-Br could be retrospectively analyzed to assess self-reported cognitive outcomes, enriching the information gained from prior research.

The present work describes the evaluation of the antidepressant-like activity of the extract, fractions, and compounds obtained from the aerial parts of Solanum capsicoides. The methanolic extract (MESC) obtained by conventional maceration was partitioned with solvents of increasing polarities yielding the respective fractions of hexane (HE), dichloromethane (DCM), and ethyl acetate (EA). The dichloromethane and ethyl acetate fractions were submitted to chromatographic and spectroscopic techniques, leading to the isolation and identification of cilistadiol (1), astragalin (2), and cilistol A (3). In relation to the antidepressant activity, the extract was active against the forced swimming test (FST) at a concentration of 300 mg/kg an ED50 (deffective dose that reduces 50% of immobility time) of 120.3 (117.3–123.4) mg/kg. Similar values were observed when evaluated in the tail suspension test (TST). In addition, the results showed no influence on motor behavior when evaluated in the open field test (OFT). Based on the observed profile of the MESC, dichloromethane fraction presenting the best profile, in both FST and TST test. Likewise, the fraction also did not present motor impairment when evaluated by the OFT test. Considering that the dichloromethane fraction was more effective, the isolated compounds cilistadiol and cilistol A were evaluated in the same experimental models. In FST, both compounds had a significant antidepressant-like effect, with ED50 values of 0.22 (0.16–0.28) and 1.03 (0.89–1.18) μmol/kg, respectively. When evaluated in the TST, showed ED50 values of 0.30 (0.18–0.52) and 1.49 (1.27–1.73) μmol/kg, respectively. The isolated compounds also did not present significant differences in the motor behavior when evaluated on OFT test in comparison with the control group. No toxicological parameters were observed until the highest dose of MESC (2000 mg/kg), demonstrating safety in the use of this plant.

Context: Pimenta dioica (L.) Merr. (Myrtaceae) is used in Costa Rican traditional medicine for women's health. Our previous work showed that P. dioica extracts were oestrogenic. Objectives: This work identifies phytochemicals from P. dioica that are responsible for the plant's oestrogen-like activities. Materials and methods: P. dioica leaves were collected in Costa Rica in 2005. Fractions resulting from chromatographic separation of a methanol extract were tested at 50 mu g/mL in a competitive oestrogen receptor-binding assay. Active compounds were isolated by HPLC and identified by NMR and MS. Pure compounds were tested at 1 mu M in the oestrogen-responsive SEAP reporter gene assay. The effects on cell viability, cytotoxicity and apoptosis were investigated in breast cancer (MCF-7 and SK-BR3) and gastric cancer (AGS and NCI-N87) cell lines using the ApoTox-Glo and Caspase-Glo assays and qPCR. Results: Quercitrin and three new chromones, including a 2-phenoxychromone, 6,8-di-C-methylcapillarisin (1) were isolated and identified. Compound 1 caused a 6.2-fold increase in SEAP expression at 1 (p<0.05). This activity was blocked by the ER antagonist ICI 182,780. Compound 2 caused a 6.0-fold increase in SEAP, inhibited the growth of MCF-7, AGS and NCI-N87 cells (IC 50 54.27, 38.13 and 51.22 mu g/mL, respectively), and induced apoptosis via caspase 8 and increased the Bax/Bcl-2 mRNA ratio in MCF-7 cells. Compound 3 was anti-oestrogenic in MCF-7 cells. Discussion and conclusions: Compounds from P. dioica have oestrogenic, anti-oestrogenic and cytotoxic effects that may explain the ethnomedical use of this plant.

Similar to their US counterparts, Costa Rican women enter menopause at ∼50 years of age, have similar symptoms, including hot flashes and night sweats, as well as an overall negative attitude toward the menopausal transition. One study of rural women in Monteverde reported that women knew little about the menopausal transition, as the subject was not discussed. Similar to other Latin American women, the use of hormone therapy by Costa Rican women is low and instead they use alternative therapies, including massage, dietary changes and herbal medicines. A wide variety of herbal therapies are used, and some of these herbs have estrogenic activities in vitro. However, clinical data on the safety and efficacy of any of these treatments is lacking. Recently, a disturbing increase in the incidence of human papilloma virus infections in menopausal women has been reported, due in part to more sexual freedom after menopause. Fortunately, the strain of HPV infecting these women is not associated with cervical cancer. Overall, there is a significant lack of scientific and medical research on menopausal women in Costa Rica. Considering the aging population, the high use of herbal medicines by menopausal women and the lack of clinical studies on these treatments, future research should focus on gaining a better understanding of menopause in this population. Furthermore, new educational programs for these women and the health professionals who serve them are necessary, as well as investigations of the safety and efficacy of the herbal supplements women use to manage their menopausal symptoms.

Human epidermal growth factor 2 (HER2) is a trans-membrane tyrosine kinase that is over expressed in 20% of breast cancers. Overexpression of HER2 has been linked to tumor proliferation and poor prognosis. Numerous studies have focused on targeting HER2 for breast cancer treatment. The leaves of Pimenta dioica (L.) Merr. (Myrtaceae), commonly known as allspice, are used in Costa Rican traditional medicine for women's health. A MeOH extract of allspice leaves collected in Costa Rica, inhibited the growth of MCF-7 (ER+, low HER2) cell proliferation with IC50 of 50 µg/ml, but were more active in SK-Br3 (ER-, high HER2) cells with an IC50 of 12.5µg/ml. In a panel of fifteen receptor tyrosine kinases (RTKs), the extract and partition inhibited two erbB RTKs, namely EGFR (HER1) and HER2 RTKs. Chromatographic separation of the EtOAc partition on a 2L C18 reversed phase silica gel column with methanol/water afforded 20 fractions. Using a high-throughput 96-well HER2 assay, the active fraction was determine to be a 50% methanol/water fraction, which also inhibited the activity of HER2 RTK. Two C-methylated flavonoids, (being new 2-phenoxychromones) were the most active with an IC50 of 1 and 5.1 µg/ml, respectively. Further preliminary data demonstrated that the 50% MeOH fraction of allspice down-regulated the expression of the HER-2 receptor protein in Western blotting and using qPCR the fraction also down-regulated the expression of the HER2 mRNA in SK-Br3 cells.

Brosimum alicastrum Swingle (Moraceae) is a large, evergreen canopy tree found throughout the Neotropics and is native to Guatemala and Costa Rica. The fruit of the tree is also known as “Mayan bread fruit” or breadnut. The seeds and the fruit of the tree have been used in traditional Mayan medicine for the treatment of menopause and osteoporosis, and are thought to have hormone-like activities. Brosimum alicastrum Swingle (Moraceae) was identified and collected under an international agreement with the University of San Carlos, and the University of Costa Rica. The fruit and leaves of the tree were collected, dried, extracted and tested in several in vitro assays to determine their biological activities, particularly for their potential estrogenic and antiestrogenic effects. Methanol extracts of the fruit displaced 3H-estradiol binding from the estrogen receptors (ERα and ERβ, EC50 48 and 49 µg/ml). Methanol extracts of the fruit pulp including seeds, and an extract of the leaves (20 µg/ml) induced a SEAP reporter gene in transiently transfected MCF-7 cells, which was inhibited by the ER antagonist ICI 182,780 indicating estrogenic effects were mediated through the ER. Conversely, a methanol extract of the fruit pulp alone was not estrogenic as compared with DMSO controls, and reduced SEAP reporter gene activity in a concentration dependent manner, suggesting potential anti-estrogenic effects.

This work deals with the synthesis and evaluation of new compounds designed by combination of 1,4-naphthoquinone and ferrocene fragments in a 3-ferrocenylmethyl-2-hydroxy-1,4-naphthoquinone arrangement. A practical coupling reaction between 2-hydroxy-1,4-naphthoquinone and ferrocenemethanol derivatives has been developed. This procedure can be carried out "on-water", at moderate temperatures and without auxiliaries or catalysts, with moderate to high yields. The synthesized derivatives have shown significant in vitro antiplasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains and it has been shown that this activity is not related to the inhibition of biomineralization of ferriprotoporphyrin IX. Binding energy calculations and docking of these compounds to cytochrome b in comparison with atovaquone have been performed.

The Central American (CA) isthmus consists of seven countries including Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama, some of the poorest countries in the world. Over the past twenty years, CA has made good progress in improving the health status of their populations. Analysis of the peer-reviewed literature, as well as national and international reports show that life expectancy at birth has increased and child mortality rates have fallen. Maternal mortality ratios (MMR) have declined by approximately 33%, however the MMRs for indigenous women remain at unacceptable levels. Despite the advances, made in many CA countries, the overall health status remains well below Latin American averages. In fact, in most CA countries, poor health outcomes are increasingly concentrated geographically among the poor and indigenous populations. Considering indigenous people make up the second largest population group in CA, any improvements in healthcare should significantly improve the health statistics for these countries. For these populations, the integration of local cultural practices and traditional healing methods with modern medicine and healthcare facilities is critical for acceptance. Investigations and analyses of local cultures, knowledge and traditional medicine practices should be used to determine the factors that contribute to poor health in these populations. Local health educational programs are needed, especially those that would involve men (spouses), families and entire communities. Furthermore, manywomen's reproductive issues still need to be addressed, particularly those that focus specifically on maternal mortality and cancer. For reductions in maternal mortality, El Salvador and Costa Rica may be good examples to follow. Access to inexpensive (or free) healthcare that is culturally sensitive and community based, particularly for indigenous women, would greatly improve the overall health. The major stumbling blocks to progress are that the funding for programs to reduce maternal mortality is woefully inadequate and that there has not been a focus on improving healthcare for indigenous women.

Ethnopharmacological relevance: Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q'egchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors.Aim of the study: To investigate the estrogenic and serotonergic activities of Piper hispidum extracts in functionalized assays, identify the active chemical constituents in the leaf extract, and test these compounds as agonists or antagonists of ER and 5-HT7.Materials and methods: The effects of the Piper hispidum leaf extracts were investigated in estrogen reporter gene and endogenous gene assays in MCF-7 cells to determine if the extracts acted as an estrogen agonist or antagonist. In addition, the active compounds were isolated using ER- and 5-HT7 receptor bioassay-guided fractionation. The structures of the purified compounds were identified using high-resolution LC-MS and NMR spectroscopic methods. The ER- and 5-HT7-agonist effects of the purified chemical constituents were tested in a 2ERE-reporter gene assay in MCF-7 cells and in serotonin binding and functionalized assays.Results: Three butenolides including one new compound (1) were isolated from the leaves of Piper hispidum, and their structures were determined. Compound 1 bound to the serotonin receptor 5-HT7 with IC50 values of 16.1 and 8.3 mu M, respectively, and using GTP shift assays, Compound 1 was found to be a partial agonist of the 5-HT7 receptor. The Piper hispidum leaf extracts, as well as Compounds 2 and 3 enhanced the expression of estrogen responsive reporter and endogenous genes in MCF-7 cells, demonstrating estrogen agonist effects.Conclusions: Extracts of Piper hispidum act as agonists of the ER and 5-HT7 receptors. Compound 1, a new natural product, identified as 9,10-methylenedioxy-5,6-Z-fadyenolide, was isolated as the 5-HT7 agonist. Compounds 2 and 3 are reported for the first time in Piper hispidum, and identified as the estrogen agonists. No inhibition of CYP450 was observed for any of these compounds in concentrations up to 1 mu M. These activities are consistent with the Q'egchi traditional use of the plant for the treatment of disorders associated with the female reproductive cycle. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

The efficient synthesis of 2-hydroxy-3-iodo-1,4-naphthoquinone (3), 2-amino-3-iodo-1,4-naphthoquinone (4), and 2-iodo-1,4-naphthoquinone (5) have been developed using the parent naphthoquinone in combination with the charge-transfer complex between iodine and morpholine.

The authors regret that under the “Acknowledgements” section the NIH grants details are unfortunately incorrect. The correct acknowledgement is written below. This study was made possible by Grants R21-AT02381-02 (GM), R01-CA130932-02 (JF), and F32-AT004876-02 (TL) from the National Institutes of Health. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or NIH. We would like to gratefully acknowledge Mr. Juan-Carlos Brenes, University of Costa Rica for his assistance in the plant collections and technical help, as well as Dr. Harry Besselink, BioDetection Systems B.V., Amsterdam, The Netherlands for his assistance with the ER_CALUX® assay. The authors would like to apologise for any inconvenience caused. Estrogenic and progestagenic effects of extracts of Justicia pectoralis Jacq., an herbal medicine from Costa Rica used for the treatment of menopause and PMSMaturitasVol. 66Issue 3PreviewTo investigate the biological activities of Justicia pectoralis Jacq. (Acanthaceae), an herbal medicine used in Costa Rica (CR) for the management of menopausal symptoms and dysmenorrhea. Full-Text PDF

OBJECTIVES:To investigate the biological activities of Justicia pectoralis Jacq. (Acanthaceae), an herbal medicine used in Costa Rica (CR) for the management of menopausal symptoms and dysmenorrhea. STUDY DESIGN:The aerial parts of J. pectoralis were collected, dried and extracted in methanol. To establish possible mechanisms of action of JP for the treatment of menopausal symptoms, the estrogenic and progesterone agonists, and antiinflammatory activities were investigated. MAIN OUTCOME MEASURES:The methanol extract (JP-M) was tested in ER and PR binding assays, a COX-2 enzyme inhibition assay, the ERbeta-CALUX assay in U2-OS cells, as well as reporter and endogenous gene assays in MCF-7 K1 cells. RESULTS:The JP-M extract inhibited COX-2 catalytic activity (IC(50) 4.8 microg/mL); bound to both ERalpha and ERbeta (IC(50) 50 microg/mL and 23.1 microg/mL, respectively); induced estrogen-dependent transcription in the ERbeta-CALUX; and bound to the progesterone receptor (IC(50) 22.8 microg/mL). The extract also modulated the expression of endogenous estrogen responsive genes pS2, PR, and PTGES in MCF-7 cells at a concentration of 20 microg/mL. Activation of a 2 ERE-construct in transiently transfected MCF-7 cells by the extract was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Finally, the extract weakly enhanced the proliferation of MCF-7 cells, however this was not statistically significant as compared with DMSO controls. CONCLUSIONS:Extracts of J. pectoralis have estrogenic, progestagenic and anti-inflammatory effects, and thus have a plausible mechanism of action, explaining its traditional use for menopause and PMS.

Objective: Outcomes from the Women's Health Initiative have demonstrated adverse effects associated with hormone therapy and have prioritized the need to develop new alternative treatments for the management of menopause and osteoporosis. To this end, we have been investigating natural herbal medicines used by Costa Rican women to manage menopausal symptoms.Methods: Seventeen plant species were collected and extracted in Costa Rica. To establish possible mechanisms of action and to determine their potential future use for menopause or osteoporosis, we investigated the estrogenic activities of the herbal extracts in an estrogen-reporter gene estrogen receptor (ER) beta-Chemically Activated Luciferase Expression assay in U2-OS cells and in reporter and endogenous gene assays in MCF-7 cells.Results: Six of the plant extracts bound to the ERs. Four of the six extracts stimulated reporter gene expression in the ER-beta-Chemically Activated Luciferase Expression assay. All six extracts modulated expression of endogenous genes in MCF-7 cells, with four extracts acting as estrogen agonists and two extracts, Pimenta dioica and Smilax domingensis, acting as partial agonist/antagonists by enhancing estradiol-stimulated pS2 mRNA expression but reducing estradiol-stimulated PR and PTGES mRNA expression. Both P. dioica and S. domingensis induced a 2ERE-luciferase reporter gene in transient transfected MCF-7 cells, which was inhibited by the ER antagonist ICI 182,780.Conclusions: This work presents a plausible mechanism of action for many of the herbal medicines used by Costa Rican women to treat menopausal symptoms. However, it further suggests that studies of safety and efficacy are needed before these herbs should be used as alternative therapies to hormone therapy.

Objectives: To investigate the attitudes and symptoms associated with the menopausal transition in Guatemalan and Costa Rican women and the therapies used to treat these symptoms.Methods: As part of an NIH funded project, interviews of women, midwives, healers and medical personnel were performed.Plants used to treat menopause were collected in Guatemala and Costa Rica, extracted and tested.Results: Women living in Central America have a more positive attitude toward menopause that their U.S. counterparts.While women in Guatemala have slightly fewer symptoms, women in Costa Rica have menopausal symptoms similar to that observed in U.S. women.However, neither women from Guatemala nor Costa Rica use HRT extensively and use herbal products instead to treat the symptoms associated with menopause.Plant species used as symptomatic treatment were collected and tested for potential biological activities.Many of the herbal remedies were active in multiple bioassays, suggesting a pleotropic and plausible mechanism of action for the treatment of anxiety, depression, vasomotor symptoms associated with the menopausal transition.Conclusions: Women in Central American countries have similar symptoms during menopause as their U.S, counterparts but have a more positive outlook on the transition, as it marks an end to the reproductive years and allows for more sexual freedom.These women however, do not use HRT to any great extent, but opt for more natural therapies such as herbal medicines and massage.Many of the herbal products used appear to have a plausible mechanism of action.

In Mexico and Central America, women typically experience menopause up to 10 years earlier than their U.S. counterparts. This may be due in part to numerous pregnancies, long periods of lactation, poor nutrition, extreme environment, and the heavy workload of the Maya women. Unlike Western culture, there is no stigma associated with aging and the menopausal period in the Mayan culture. In fact, menopause is considered to be a welcome natural phenomenon in Central America that all Maya women, who come of age, will experience. Anxiety, negative attitudes, health concerns and stress for the Maya woman are all events that are commonly associated with pregnancy and childbearing, not with menopause. Maya women perceive the menopausal period very positively, as they are no longer burdened with menstrual bleeding and child bearing, and are more relaxed about sexual activities.Thus, compared with their U.S. counterparts, Maya women have a better overall perceptions and attitudes toward the menopausal transition, have symptoms that appear to be short-lived, do not generally use HRT and appear to have a lower prevalence of osteoporosis. Besides genetics, diet and life-style may play a significant role in the overall impact of menopause in these women, as their diet is primarily plant-based, they get plenty of exercise over a lifetime, and they use primarily plant-based medicines and ma ssage to control menopausal symptoms. Thus, the impact of culture and attitude on the menopausal transition in Mexico and Central America appears to be a positive one. Future research should focus on why the prevalence of osteoporosis is low in Maya women and how women in the U.S. might benefit from this information. In addition, collections of data on cognition, as well as cardiovascular and cancer risk between these groups would be of benefit, considering that Maya women do not generally use HRT.