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1.
Public Health Pract (Oxf) ; 7: 100512, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38846106

RESUMEN

Objectives: Research on links between social, geographic, and cultural determinants of health has been thwarted by inadequate measures of culture. The purpose of this study was to improve the measurement of community culture, defined as shared patterns of attitudes and behaviors among people within a neighborhood that distinguish it from others, and to examine dimensions of culture, independent of socioeconomic and demographic factors, and their relationships with health. Study design: A survey research design with correlational analyses was used. Methods: A survey packet including the Community Culture Survey - Revised (CCS-R), demographic, health, and other individual-level measures was administered through convenience sampling across the United States (US) and to a sample in Thailand from 2016 to 2018. US county-level variables were obtained from zip codes. Results: 1930 participants from 49 US states (n = 1592) and Thailand (n = 338) completed all CCS-R items, from which 12 subscales were derived: Social Support & Connectedness, Responsibility for Self & Others, Family Ties & Duties, Social Distress, Urban Diversity, Discontinuity, Church-Engaged, External Resource-Seeking, Locally Owned Business-Active, Power Deference, Next Generation Focus, and Self-Reliance. Neighborhood culture subscale scores varied more by geography than by participant's demographics. All subscales predicted one or more health indicator, and some of these relationships were significant after adjusting for participant age and county-level socioeconomic variables. Most of the significant differences on subscales by race/ethnicity were no longer significant after adjusting for participant's age and county-level socioeconomic variables. Most rural/urban and regional differences in culture within the US persisted after these adjustments. Based on correlational analyses, Social Support & Connectedness and Responsibility for Self & Others were the best predictors of participants' overall health and quality of life, and Responsibility for Self & Others was the best predictor (inversely) of the CDC's measures of social vulnerability. Conclusions: Neighborhood culture is measurable, multi-dimensional, distinct from race/ethnicity, and related to health even after controlling for age and socioeconomic factors. The CCS-R is useful for advancing research and practice addressing the complex interactions between individuals, their neighborhood communities, and health outcomes.

2.
ACS Omega ; 9(16): 18516-18525, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38680310

RESUMEN

The fruit extract of Melaleuca quinquenervia yielded a total of 19 compounds, including two novel spiro-biflavonoid enantiomers (1a and 1b) and a chalcone derivative (3). Their structures were determined through spectroscopic analysis. The enantiomers of the racemic mixture of compound 1 were successfully resolved into (+)-1 and (-)-1 using chiral-phase HPLC. Single-crystal X-ray diffraction analysis was also used to confirm the structure of 1. The enantiomeric configurations of 1 and 2 were determined through a comparison of the calculated and experimental electronic circular dichroism spectra. Compounds 2 (melanervin), 14 (methyl betulinate), 15 (3-O-acetylbetulinic acid), and 16 (pyracrenic acid) were found to be highly cytotoxic, with compound 16 showing superior growth inhibition of nonsmall cell lung cancer cells (A549 cells) (IC50 2.8 ± 0.1 µM) compared to cisplatin (IC50 3.3 ± 0.0 µM), a positive control chemotherapeutic drug. Both compound 16 and cisplatin were significantly more cytotoxic toward A549 lung cancer cells compared to nontumorigenic Vero E6 cells.

3.
Toxicol Rep ; 12: 224-233, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38328737

RESUMEN

Background: Boesenbergia rotunda (fingerroot) rhizome extract contains two major bioactive components, panduratin A and pinostrobin. In our previous study, we found the anti-inflammatory effects of the fingerroot extract against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in golden Syrian hamsters. In the present study, we evaluated the sub-chronic toxicity of a fingerroot extract formulation over 90 consecutive days of oral administration. Methods: We enhanced the water solubility of a fingerroot extract by formulating it with cyclodextrin, containing panduratin A (29% w/w) and pinostrobin (32% w/w). This formulation was administered to male and female Wistar rats at doses of 25, 50, or 100 mg/kg/day for a duration of 90 days. Additionally, two recovery groups, comprising a control group and a high-dose group, were designated for a 14-day observation period to assess the persistence and reversibility of potential adverse effects. Throughout the experiment, we performed clinical and health observations, followed by hematological testing, clinical biochemistry analysis, necropsy examination, and histopathological evaluation at the end of the experiment. Results: The administration of the fingerroot extract formulation at doses of 25, 50, or 100 mg/kg/day did not result in mortality or clinical signs of toxicity. No clinically significant findings were associated with the oral administration of the fingerroot extract formulation. Conclusion: The fingerroot extract formulation showed no serious adverse effects at doses up to 100 mg/kg/day in Wistar rats under the experimental condition. Consequently, the No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg/day. This finding contributes significance for future developments involving fingerroot extract in herbal medicinal products targeting chronic inflammation.

4.
J Nat Prod ; 86(2): 276-289, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36746775

RESUMEN

Sixteen new quinoline alkaloids (1a-7, 8a, 9, 10, 13-15, 17, and 21) and 10 known analogs (8b, 11, 12, 16, 18-20, and 22-24), along with three known cyclopeptide alkaloids (25-27), were isolated from the roots of Waltheria indica. The structures of the new compounds were elucidated by detailed NMR and circular dichroism with computational support and mass spectrometry data interpretation. Anti-inflammatory potential of isolates was evaluated based on inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity with cell culture models. In the absence of cell growth inhibition, compounds 6, 8a, 9-11, 13, 21, and 24 reduced TNF-α-induced NF-κB activity with IC50 values ranging from 7.1 to 12.1 µM, comparable to the positive control (BAY 11-7082, IC50 = 9.7 µM). Compounds 6, 8a, 8b, and 11 showed significant NO-inhibitory activity with IC50 values ranging from 11.0 to 12.8 µM, being more active than the positive control (l-NMMA, IC50 = 22.7 µM). Structure-activity relationships indicated that NO inhibitory activity was significantly affected by C-8 substitution. Inhibition of LPS-induced nitric oxide synthase (iNOS) by 8b [(5S)-waltherione M, IC50 11.7 ± 0.8 µM] correlated with inhibition of iNOS mRNA expression. The biological potential of W. indica metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.


Asunto(s)
Alcaloides , Malvaceae , Quinolinas , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Lipopolisacáridos/farmacología , Alcaloides/farmacología , Antiinflamatorios/farmacología , Malvaceae/química , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico
5.
Molecules ; 27(10)2022 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-35630746

RESUMEN

Seven new coumarinolignans, walthindicins A-F (1a, 1b, 2-5, 7), along with five known analogs (6, 8-11), were isolated from the roots of Waltheria indica. The structures of the new compounds are determined by detailed nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. Compounds were tested for their antioxidant activity in Human Cervical Cancer cells (HeLa cells). Compounds 1a and 6 showed higher reactive oxygen species (ROS) inhibitory activity at 20 µg/mL when compared with other natural compound-based antioxidants such as ascorbic acid. Considering the role of ROS in nuclear-factor kappa B (NF-κB) activation, compounds 1a and 6 were evaluated for NF-κB inhibitory activity and showed a concentration-dependent inhibition in Human Embryonic Kidney 293 cells (Luc-HEK-293).


Asunto(s)
Cumarinas , Lignanos , Malvaceae , FN-kappa B , Especies Reactivas de Oxígeno , Cumarinas/química , Cumarinas/farmacología , Células HEK293 , Células HeLa , Humanos , Lignanos/química , Lignanos/farmacología , Malvaceae/química , FN-kappa B/antagonistas & inhibidores , Fitoquímicos/química , Fitoquímicos/farmacología , Raíces de Plantas/química , Especies Reactivas de Oxígeno/antagonistas & inhibidores
6.
Artículo en Inglés | MEDLINE | ID: mdl-35436745

RESUMEN

Rat lungworm (Angiostrongylus cantonensis) is a neurotropic nematode, and the leading cause of eosinophilic meningitis worldwide. The parasite is usually contracted through ingestion of infected gastropods, often hidden in raw or partially cooked produce. Pharmaceutical grade pyrantel pamoate was evaluated as a post-exposure prophylactic against A. cantonensis. Pyrantel pamoate is readily available over-the-counter in most pharmacies in the USA and possesses anthelmintic activity exclusive to the gastrointestinal tract (GIT). Administering pyrantel pamoate immediately after exposure should theoretically paralyze the larvae in the GIT, causing the larvae to be expelled via peristalsis without entering the systemic circulation. In this study, pyrantel pamoate (11 mg/kg) was orally administered to experimentally infected rats at 0, 2-, 4-, 6-, or 8-h post-infection. The rats were euthanized six weeks post-infection, and worm burden was evaluated from the heart-lung complex. This is the first in vivo study to evaluate its efficacy against A. cantonensis. This study demonstrates that pyrantel pamoate can significantly reduce worm burden by 53-72% (P = 0.004), and thus likely reduce the severity of infection that is known to be associated with worm burden. This paralyzing effect of pyrantel pamoate on the parasite may also be beneficial for delaying the establishment of infection until a more suitable anthelmintic such as albendazole is made available to the patient.


Asunto(s)
Angiostrongylus cantonensis , Antihelmínticos , Albendazol , Animales , Antihelmínticos/uso terapéutico , Pamoato de Pirantel/uso terapéutico , Ratas
7.
Pharmaceuticals (Basel) ; 15(2)2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35215264

RESUMEN

More than half of Thai patients with cancer take herbal preparations while receiving anticancer therapy. There is no systematic or scoping review on interactions between anticancer drugs and Thai herbs, although several research articles have that Thai herbs inhibit cytochrome P450 (CYP) or efflux transporter. Therefore, we gathered and integrated information related to the interactions between anticancer drugs and Thai herbs. Fifty-two anticancer drugs from the 2020 Thailand National List of Essential Medicines and 75 herbs from the 2020 Thai Herbal Pharmacopoeia were selected to determine potential anticancer drug-herb interactions. The pharmacological profiles of the selected anticancer drugs were reviewed and matched with the herbal pharmacological activities to determine possible interactions. A large number of potential anticancer drug-herb interactions were found; the majority involved CYP inhibition. Efflux transporter inhibition and enzyme induction were also found, which could interfere with the pharmacokinetic profiles of anticancer drugs. However, there is limited knowledge on the pharmacodynamic interactions between anticancer drugs and Thai herbs. Therefore, further research is warranted. Information regarding interactions between anticancer drugs and Thai herbs should provide as a useful resource to healthcare professionals in daily practice. It could enable the prediction of possible anticancer drug-herb interactions and could be used to optimize cancer therapy outcomes.

8.
Int J Clin Pharm ; 44(2): 348-356, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34811600

RESUMEN

Background Community pharmacists have a role in identifying drug-drug interactions (DDIs) when processing prescription orders and dispensing medications to patients. The harmful effects of DDIs can be prevented or minimized by using an electronic DDI checker to screen for potential DDIs (pDDIs). However, different DDI checkers have variable rates of detecting pDDIs. Aim To estimate the prevalence of pDDIs in prescriptions dispensed in a community pharmacy setting using two electronic DDI databases and to evaluate the association between the pDDIs and contributory factors. Method Eligible prescription orders dispensed by a community pharmacy chain in Qatar from January to July 2020 were included in this retrospective observational study. For each prescription, Micromedex® and Lexicomp® were simultaneously used to identify pDDIs, and the interactions categorized based on severity and risk rating. Results Seven hundred-twenty prescriptions met the inclusion criteria, of which Micromedex® and Lexicomp® respectively identified 125 prescriptions (17.4%) and 230 prescriptions (31.9%) as having at least one pDDI. Moderate strength of agreement was found between Lexicomp® and Micromedex® in identifying pDDIs (Cohen's Kappa = 0.546). Micromedex® classified 61.6% of DDIs as major severity, while Lexicomp® classified 30.8% as major severity. The number of concurrent medications per prescription was significantly and positively associated with pDDI. Conclusion This study demonstrates a high prevalence of pDDIs among prescriptions dispensed in a community pharmacy setting. It is advisable that community pharmacists in Qatar, who typically do not have access to computerized patient profiles, use these DDI checkers to ensure all pDDIs are communicated to respective prescribers for appropriate action.


Asunto(s)
Farmacias , Interacciones Farmacológicas , Humanos , Farmacéuticos , Prescripciones , Estudios Retrospectivos
10.
Curr Pharm Teach Learn ; 13(2): 134-138, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33454069

RESUMEN

INTRODUCTION: This project utilized the social media platform Instagram, which focuses upon posting images with accompanied captions, as a supplemental learning tool. The objective was to assess the impact of using a clinical pharmacy-focused Instagram account on students' knowledge of ambulatory care pharmacy. METHODS: A pre- and posttest quasi-experimental design was conducted in a third-year introductory pharmacy practice experience course during fall 2018. Pharmacy students were notified of the availability of an Instagram account managed by the principal investigator that posted ambulatory care clinical pearls as an optional supplemental educational tool. The primary outcome evaluated change in scores from pre- to posttest for the cohort of students in this course who followed the Instagram account (intervention group) compared to the cohort of students who did not follow the account (control group). RESULTS: A total of 69 third-year pharmacy students completed the course, with 37 students choosing not to follow the Instagram account (control group) and 32 students opting to engage with the Instagram account (intervention group). Pretest mean scores were nonsignificant between groups. The intervention group resulted in a higher increase in mean scores from pre- to the posttest (15% vs. 3.1%). CONCLUSIONS: Use of an educational Instagram account had a positive impact on students' knowledge relating to ambulatory care pharmacy as demonstrated by this comparison study.


Asunto(s)
Atención Ambulatoria , Educación en Farmacia , Servicio de Farmacia en Hospital , Medios de Comunicación Sociales , Estudiantes de Farmacia , Evaluación Educacional , Humanos
11.
J Nat Prod ; 83(7): 2233-2240, 2020 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-32568536

RESUMEN

Five new lumazine peptides (1-5), a new aspochalasin derivative (6), and a new γ-butyrolactone derivative (7), together with seven known compounds (8-14), were isolated from a Hawaiian fungal strain, Aspergillus flavipes FS888. Compound 1 is an uncommon natural product containing an isocyano group. The structures of the new compounds 1-7 were elucidated by NMR spectroscopy, HRESIMS, chemical derivatization, and ECD analysis. Compounds 12-14 showed significant antibacterial activity against S. aureus when in combination with disulfiram. Additionally, compounds 9 and 13 showed NF-κB inhibitory activity with IC50 values of 3.1 ± 1.0 and 10.3 ± 2.0 µM, respectively.


Asunto(s)
4-Butirolactona/química , Antibacterianos/farmacología , Aspergillus/química , Proteínas Fúngicas/química , FN-kappa B/antagonistas & inhibidores , Péptidos/química , Péptidos/farmacología , Proteínas Fúngicas/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Péptidos/aislamiento & purificación , Análisis Espectral/métodos , Staphylococcus aureus/efectos de los fármacos
12.
PLoS One ; 14(11): e0225239, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31725785

RESUMEN

BACKGROUND: Drug-drug interactions (DDIs) are one of the most common drug-related problems. Recently, electronic databases have drug interaction tools to search for potential DDIs, for example, Micromedex and Drugs.com. However, Micromedex and Drugs.com have different abilities in detecting potential DDIs, and this might cause misinformation to occur between patients and health care providers. METHODS AND FINDINGS: The aim of this study was to compare the ability of Micromedex and Drugs.com to detect potential DDIs with metabolic syndrome medications using the drug list from the U-central database, King Chulalongkorn Memorial Hospital in April 2019. There were 90 available drugs for the treatment of the metabolic syndrome and its associated complications, but six were not found in the Micromedex and Drugs.com databases; therefore, only 84 items were used in the present study. There were 1,285 potential DDI pairs found by the two databases. Micromedex reported DDIs of 724 pairs, while, Drugs.com reported 1,122 pairs. For the severity of the potential DDI reports, the same severity occurred between the two databases of 481 pairs (37.43%) and a different severity for 804 pairs (62.57%). CONCLUSION: Drugs.com had a higher sensitivity to detect potential DDIs by approximately 1.5-fold, but Micromedex supplied more informative documentation for the severity classification. Therefore, pharmacists should use at least two databases to evaluate potential DDIs and determine the appropriate drug regimens for physician communications and patient consultations.


Asunto(s)
Interacciones Farmacológicas , Síndrome Metabólico/tratamiento farmacológico , Bases de Datos Farmacéuticas , Manejo de la Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico , Índice de Severidad de la Enfermedad
13.
J Nat Prod ; 82(8): 2124-2131, 2019 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-31411887

RESUMEN

Twelve sesquiterpene lactones were isolated from the whole plants of Vernonia cinerea. These included eight new compounds, vercinolides A-H (1-8), along with four known substances (9-12). The structures of the new compounds were determined by 1D and 2D NMR experiments and mass spectrometric methods. The absolute configurations of compounds 1-8 were determined by Mosher experiments and ECD data. Compounds 1-8 are the first examples of a new class of sesquiterpene lactones possessing a rare 4α,10α-ether ring and a 2,14-ether ring. Compounds 1-4, 6, 8, 10, and 12 were evaluated for their cytotoxic and anti-inflammatory activities. Compounds 10 and 12 exhibited inhibitory effects against nitric oxide production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC50 values of 21 and 23 µM, respectively. Both compounds were inactive for HeLa cells (IC50 > 10 µM).


Asunto(s)
Lactonas/aislamiento & purificación , Sesquiterpenos/aislamiento & purificación , Vernonia/química , Animales , Antineoplásicos/farmacología , Células HeLa , Humanos , Lactonas/química , Lactonas/farmacología , Ratones , Estructura Molecular , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/farmacología , Análisis Espectral/métodos
14.
J Microbiol Biotechnol ; 28(6): 1007-1021, 2018 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-29847866

RESUMEN

Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and 200 µg/ml cWBC exhibits a strong cytotoxic effect against all investigated cell lines (IC50 70.34-101.0 µg/ml), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the S-G2/M transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.


Asunto(s)
Caimanes y Cocodrilos , Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Extractos Celulares/farmacología , Proliferación Celular/efectos de los fármacos , Leucocitos/química , Animales , Antineoplásicos/aislamiento & purificación , Ciclo Celular/efectos de los fármacos , Extractos Celulares/aislamiento & purificación , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Especies Reactivas de Oxígeno/metabolismo
15.
J Neurol Sci ; 385: 168-174, 2018 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29406900

RESUMEN

BACKGROUND: Orthostatic hypotension (OH) is a commonly reported sign of the cardiovascular autonomic dysfunctions associated with Parkinson's disease (PD). Patients might suffer from a variety of the clinical symptoms of OH, including dizziness, lightheadedness, or problems with vision and fatigue. OBJECTIVES: To determine the prevalence of, and factors associated with, symptomatic orthostatic hypotension (OH) in Parkinson's disease (PD) and to identify any relationships between the clinical symptoms of OH and balance confidence in this patient population. METHODS: Symptomatic OH was defined as a systolic or diastolic BP fall of ≥20 or ≥10mmHg respectively, within 3min of standing and an Orthostatic Hypotension Questionnaire (OHQ) score of more than zero. Factors related to symptomatic OH were identified from a multivariate logistic regression analysis. Pearson's correlation test was used to reveal any relationships between the clinical symptoms of OH and a patient's confidence in their ability to balance, assessed using the Activities-specific Balance Confidence (ABC) scale. RESULTS: 100 Thai PD patients were consecutively recruited into this study. The prevalence of symptomatic OH was 18%, asymptomatic OH was 4%, while 78% were patients without OH. Factors associated with symptomatic OH were age (OR, 95%CI: 1.06, 1.003-1.115, p=0.038) and hypertension (OR, 95%CI: 6.16, 1.171-32.440, p=0.032). A significant and negative correlation (r=-0.229, p=0.022) between OHQ composite scores and item 3 of the ABC scale (picking up slippers from floor), one of the movements in a vertical orientation, was found. CONCLUSION: Elderly PD patients and with a co-morbidity of essential hypertension should be closely evaluated for the presence of symptomatic OH. In addition, they should be advised to change positions slowly, especially those in a vertical orientation.


Asunto(s)
Hipotensión Ortostática/epidemiología , Hipotensión Ortostática/etiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Equilibrio Postural , Anciano , Presión Sanguínea , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Encuestas y Cuestionarios
16.
J Med Chem ; 58(19): 7734-48, 2015 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-26331426

RESUMEN

We report that hirsutinolide series, 6, 7, 10, 11, 20, and 22, and the semisynthetic analogues, 30, 31, 33, and 36, inhibit constitutively active signal transducer and activator of transcription (Stat)3 and malignant glioma phenotype. A position 13 lipophilic ester group is required for activity. Molecular modeling and nuclear magnetic resonance structural analyses reveal direct hirsutinolide:Stat3 binding. One-hour treatment of cells with 6 and 22 also upregulated importin subunit α-2 levels and repressed translational activator GCN1, microtubule-associated protein (MAP)1B, thioredoxin reductase (TrxR)1 cytoplasmic isoform 3, glucose-6-phosphate 1-dehydrogenase isoform a, Hsp105, vimentin, and tumor necrosis factor α-induced protein (TNAP)2 expression. Active hirsutinolides inhibited anchorage-dependent and three-dimensional spheroid growth, survival, and migration of human glioma lines and glioma patients' tumor-derived xenograft cells harboring constitutively active Stat3. Oral gavage delivery of 6 or 22 inhibited human glioma tumor growth in subcutaneous mouse xenografts. The inhibition of Stat3 signaling represents part of the hirsutinolide-mediated mechanisms to induce antitumor effects.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Animales , Antineoplásicos/síntesis química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos/métodos , Femenino , Glioma/metabolismo , Glioma/patología , Glucosafosfato Deshidrogenasa/metabolismo , Proteínas del Choque Térmico HSP110/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Ratones Desnudos , Proteínas Asociadas a Microtúbulos/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Relación Estructura-Actividad , Tiorredoxina Reductasa 1/metabolismo , Transactivadores/metabolismo , Vimentina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , alfa Carioferinas/metabolismo
17.
Int J Clin Pharm ; 36(4): 771-8, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24853094

RESUMEN

BACKGROUND: Vitamin D deficiency is a common problem worldwide. Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome. No previous study has compared the efficacy and safety of ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic syndrome. OBJECTIVE: To evaluate the efficacy of ergocalciferol supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and to examine safety parameters in metabolic syndrome patients. SETTING: Outpatient department of Phramongkutklao Hospital, Bangkok, Thailand. METHOD: A randomized, double-blinded, parallel study was conducted in metabolic syndrome patients with vitamin D deficiency [25(OH)D <20 ng/mL]. Ninety patients were randomly assigned into three groups of 30 patients each. Group 1 was given two capsules of placebo/week, group 2 was given ergocalciferol 20,000 IU/week, and group 3 was given ergocalciferol 40,000 IU/week for 8 weeks. MAIN OUTCOME MEASURE: serum 25(OH)D concentrations, serum calcium, safety, and corrected QT (QTc) interval. RESULTS: Of the 90 patients enrolled, 84 patients completed the study. At the end of the study, the mean serum 25(OH)D in groups 2 and 3 significantly increased from the baseline (15.1 and 14.3 to 26.8 and 30.0 ng/mL, respectively). The increase in serum 25(OH)D in groups 2 and 3 were comparable and significantly greater than that of the placebo group. The percentage number of patients achieving normal vitamin D levels in groups 1, 2 and 3 were 3.3, 33.3, and 60.0 %, respectively, which were significantly different between groups (p < 0.001). Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group (p > 0.05). Serum calcium levels did not change within and between groups of treatment. No significant change in QTc was observed in any patient. CONCLUSIONS: Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were able to increase serum 25(OH)D concentrations significantly. However, more patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal serum 25(OH)D level than in the group which received 20,000 IU/week. Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients.


Asunto(s)
Suplementos Dietéticos , Ergocalciferoles/administración & dosificación , Síndrome Metabólico/complicaciones , Deficiencia de Vitamina D/dietoterapia , 25-Hidroxivitamina D 2/sangre , Anciano , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/prevención & control , Calcifediol/sangre , Calcio/sangre , Método Doble Ciego , Ergocalciferoles/efectos adversos , Ergocalciferoles/uso terapéutico , Femenino , Humanos , Hipercalcemia/inducido químicamente , Hipercalcemia/epidemiología , Hipercalcemia/etiología , Hipercalcemia/prevención & control , Incidencia , Masculino , Persona de Mediana Edad , Tailandia/epidemiología , Factores de Tiempo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/fisiopatología
18.
Fitoterapia ; 93: 194-200, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24370662

RESUMEN

Four new sesquiterpene lactones, 8α-(2'Z-tigloyloxy)-hirsutinolide (1), 8α-(2'Z-tigloyloxy)-hirsutinolide-13-O-acetate (2), 8α-(4-hydroxytigloyloxy)-hirsutinolide (3), and 8α-hydroxy-13-O-tigloyl-hirsutinolide (4), along with seven known derivatives (5-11), three norisoprenoids (12-14), a flavonoid (15), and a linoleic acid derivative (16), were isolated from the chloroform partition of a methanol extract from the combined leaves and stems of Vernonia cinerea. Their structures were established by 1D and 2D NMR, UV, and MS analyses. Compounds 1-16 were evaluated for their inhibitory effects against the viability of U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbour aberrantly-active STAT3, compared to normal NIH3T3 mouse fibroblasts that show no evidence of activated STAT3. Among the isolates, compounds 2 and 7 inhibited the aberrant STAT3 activity in glioblastoma or breast cancer cells. Further, compounds 7 and 8 inhibited viability of all three cell lines, compounds 2, 4, and 9 predominantly inhibited the viability of the U251MG glioblastoma cell line.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Lactonas/aislamiento & purificación , Factor de Transcripción STAT3/antagonistas & inhibidores , Sesquiterpenos/aislamiento & purificación , Vernonia/química , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Lactonas/química , Estructura Molecular , Sesquiterpenos/química
19.
Am J Pharm Educ ; 77(7): 153, 2013 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-24052656

RESUMEN

OBJECTIVE: To compare second- and third-year pharmacy students' competence, attitudes, and self-confidence in providing diabetes care before and after completing a hand-on diabetes training program and to determine if the program had an impact on students' attitude and self-confidence based on their year in the curriculum. DESIGN: The program included classroom lectures and hands-on learning sessions in 5 facets of diabetes care. Pre- and post-test instruments measured students' competence, attitudes, and confidence in diabetes care. ASSESSMENT: Students' competence and the mean overall confidence score significantly improved after completing the program, while mean overall attitude score did not. Third-year students had significantly higher confidence scores than did second-year students on both pre- and post-program tests. No significant difference was found for attitude scores between second- and third-year students. CONCLUSION: The hands-on learning program was an effective approach to training pharmacy students in diabetes care, improving both their competence and confidence.


Asunto(s)
Curriculum , Diabetes Mellitus , Educación en Farmacia , Educación , Conocimientos, Actitudes y Práctica en Salud , Estudiantes de Farmacia , Evaluación Educacional , Humanos
20.
Bioorg Med Chem Lett ; 22(17): 5559-62, 2012 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-22850207

RESUMEN

Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison with the structure of compound 1, whose relative stereochemistry was determined by X-ray analysis. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-α-induced NF-κB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6 µM, respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4 µM, respectively.


Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Lactonas/química , Lactonas/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Vernonia/química , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Cristalografía por Rayos X , Flores/química , Humanos , Lactonas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Ratones , Modelos Moleculares , FN-kappa B/inmunología , Neoplasias/prevención & control , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Sesquiterpenos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/inmunología
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