High-Throughput Sequencing of Grapevine in Mexico Reveals a High Incidence of Viruses including a New Member of the Genus Enamovirus.

This is the first viral metagenomic analysis of grapevine conducted in Mexico. During the summer of 2021, 48 plants displaying virus-like symptoms were sampled in Queretaro, an important grapevine-producing area of Mexico, and analyzed for the presence of viruses via high-throughput sequencing (HTS). The results of HTS were verified by real-time RT-PCR following a standardized testing scheme (Protocol 2010). Fourteen different viruses were identified, including grapevine asteroid mosaic-associated virus (GAMaV), grapevine Cabernet Sauvignon reovirus (GCSV), grapevine fanleaf virus (GFLV), grapevine fleck virus (GFkV), grapevine Pinot gris virus (GPGV), grapevine red globe virus (GRGV), grapevine rupestris stem pitting-associated virus (GRSPaV), grapevine rupestris vein feathering virus (GRVFV), grapevine Syrah virus 1 (GSyV-1), grapevine virus B (GVB), and grapevine leafroll-associated viruses 1, 2, 3, 4 (GLRaV1, 2, 3, 4). Additionally, divergent variants of GLRaV4 and GFkV, and a novel Enamovirus-like virus were discovered. This is the first report of GAMaV, GCSV, GLRaV4, GPGV, GRGV, GRVFV, and GSyV-1 infecting grapevines in Mexico; the impact of these pathogens on production is unknown.

Viruses of Economic Impact on Tomato Crops in Mexico: From Diagnosis to Management-A Review.

Tomato is the most economically important vegetable crop worldwide and the second most important for Mexico. However, viral diseases are among the main limiting factors that affect the productivity of this crop, causing total losses in some cases. This review provides key information and findings on the symptoms, distribution, transmission, detection, and management of diseases caused by viruses of major importance in tomato crops in Mexico. Currently, about 25 viruses belonging to nine different families have been reported infecting tomato in Mexico, but not all of them cause economically significant diseases. Viruses of economic importance include tomato brown rugose fruit virus (ToBRFV), tomato spotted wilt virus (TSWV), tomato yellow leaf curl virus (TYLCV), pepino mosaic virus (PepMV), and tomato marchitez virus (ToMarV). The topics discussed here will provide updated information about the status of these plant viruses in Mexico as well as diverse management strategies that can be implemented according to the specific circumstances of each viral pathosystem. Additionally, a list of tomato-affecting viruses not present in Mexico that are continuous threats to the crop health is included.

Minireview: Situación actual del cáncer de cuello uterino en Ecuador, 2019 / Minireview: Current situation of cervical cancer in Ecuador, 2019

El cáncer de cuello uterino (CCU) es una neoplasia producida principalmente por el virus del papiloma humano (VPH), mismo que se adquiere a través del contacto sexual. El CCU tiene mayor prevalencia en países de ingresos medios y bajos, el 88% de muertes por esta causa a nivel mundial, se producen en países en vías de desarrollo, tales como el Ecuador. El proyecto ELEVATE (Early detection of cervical cancer in hard-to-reach populations of women through portable and point- of-care HPV testing), financiado por la Unión Europea, busca caracterizar el contexto nacional de esta enfermedad; con esta finalidad, se realizó una búsqueda sistemática de artículos científicos y de literatura gris, producida en el Ecuador, utilizando motores de búsqueda especializados, y repositorios virtuales institucionales, de universidades e instancias gubernamentales.(au)

Cervical cancer is a neoplasm mainly caused by the human papillomavirus (HPV), which is acquired through sexual contact. Cervical cancer is more prevalent in low and middle income countries; 88% of worldwide deaths from this cause, occur in developing countries, such as Ecuador. The ELEVATE project (Early detection of cervical cancer in hard-to-reach populations of women through portable and point-of-care HPV testing), funded by the European Union, seeks to characterize the national context of this disease; with this purpose, we carried out a systematic search for scientific articles and gray literature, produced in Ecuador, using specialized search engines, and virtual repositories from universities and government institutions.(au)

Estudio Transversal: Prevalencia de Infecciones por Virus Sincitial Respiratorio en Pacientes Ingresados en el Hospital de Especialidades José Carrasco Arteaga, 2017 / Cross- sectional study: Prevalence of Human Respiratory Syncytial Virus Infections in Patients Admitted at the Hospital José Carrasco Arteaga, 2017

INTRODUCCIÓN: El virus sincitial respiratorio es una de las principales causas de infección respiratoria baja en pacientes menores de 5 años; constituye además una de las principales causas de mortalidad pediátrica a nivel mundial. El objetivo del presente estudio fue determinar la prevalencia de infección por virus sincitial respiratorio en pacientes ingresados en el Hospital de Especialidades José Carrasco Arteaga. METODOLOGÍA: Se realizó un estudio transversal, el universo incluyó a pacientes pediátricos con edades comprendidas entre los 0 y 5 años, que hayan sido ingresados en el Hospital de Especialidades José Carrasco Arteaga con diagnóstico de infección respiratoria baja. Se usó la inmunocromatografía como prueba para detección del virus, los datos fueron tabulados mediante el programa estadístico SPSS versión 22.0. RESULTADOS: 186 pacientes fueron incluidos en el estudio; de estos el 76.35% (n=142) fue diag-nosticado de neumonía, 19.35% (n=36) de bronquiolitis y 4.30% (n=8) de bronquitis aguda. La prevalencia de infecciones por virus sincitial respiratorio en pacientes pediátricos fue del 44% (n=82). Los factores analizados en busca de asociación con la infección fueron: edad 24 ­ 60 meses (p= 0.012), sexo masculino (p= 0.236), parto por cesárea (p= 0.853), patología crónica de base (p=0.060), esquema de vacunación incompleto (p= 0.010), lactancia materna no exclusiva (p= 0.176), tabaquismo pasivo (p= 0.609) y nivel socio económico bajo (p= 0.609). CONCLUSIÓN: La prevalencia general de infección por virus sincitial respiratorio en pacientes menores a 5 años es del 43%. De los factores analizados, la edad (24 ­ 60 meses) y el esquema de vacu-nación incompleto presentaron asociación estadísticamente significativa con la presencia de la infección. Esta investigación no reportó asociación con sexo masculino, parto por cesárea, patología crónica de base, lactancia materna incompleta, tabaquismo previo o nivel socio económico bajo.(AU)

BACKGROUND: Human Respiratory Syncytial Virus is one of the main causes of lower respiratory infections in patients under 5 years of age; it is also one of the main causes of pediatric mortality worldwide. The aim of this study was to determine the prevalence of respiratory syncytial virus infection in patients admitted to Hospital José Carrasco Arteaga. METHODS: A cross-sectional study was performed; the universe included pediatric patients between 0 and 5 years old, who had been admitted to Hospital José Carrasco Arteaga with a diagnosis of low respiratory infection. Immunochromatography was used as a test for virus detection; the data was tabulated using the statistical software SPSS version 22.0. RESULTS: 186 patients were included; 76.35% (n=142) were diagnosed with pneumonia, 19.35% (n=36) of bronchiolitis and 4.30% (n=8) of acute bronchitis. The prevalence of human respiratory syncytial virus infections in pediatric patients was 44% (n=82). The factors analyzed in search of association with the infection were: age 24 - 60 months (p= 0.012), male sex (p= 0.236), cesarean delivery (p= 0.853), chronic base pathology (p= 0.060), incomplete vaccination scheme (p= 0.010), non-exclusive breastfeeding (p= 0.176), passive smoking (p= 0.609) and low socio-economic status (p= 0.609). CONCLUSION: The overall prevalence of human respiratory syncytial virus infection in patients younger than 5 years is 43%. Of the analyzed factors, age (24 - 60 months) and incomplete vaccination scheme showed a statistically significant association with the presence of the infection. This investigation did not report association with male sex, cesarean delivery, chronic basic pathology, incomplete breastfeeding, previous smoking or low socio-economic status.

Acrocomia crispa fruits lipid extract prevents LPS-induced acute lung injury in mice / Extracto lipídico de los frutos de Acrocomia crispa previene el daño pulmonar agudo inducido por LPS en ratones

The aim of this study was to evaluate the effects of single oral doses of D-005 (a lipid extract obtained from the fruit oil of Acrocomia crispa) on LPS-induced acute lung injury (ALI) in mice. D-005 batch composition was: lauric (35.8%), oleic (28.4%), myristic (14.2%), palmitic (8.9%), stearic (3.3%), capric (1.9%), caprylic (1.2%), and palmitoleic (0.05%) acids, for a total content of fatty acids of 93.7%. D-005 (200 mg/kg) significantly reduced lung edema (LE) (≈ 28% inhibition) and Lung Weight/Body Weight ratio (LW/BW) (75.8% inhibition). D-005 (25, 50, 100 and 200 mg/kg) produced a significant reduction of Histological score (59.9, 56.1, 53.5 and 73.3% inhibition, respectively). Dexamethasone, as the reference drug, was effective in this experimental model. In conclusion, pretreatment with single oral doses of D-005 significantly prevented the LPS-induced ALI in mice.

El objetivo de este estudio fue evaluar los efectos de dosis orales únicas de D-005 (extracto lipídico obtenido del aceite de frutos de Acrocomia crispa) sobre el daño pulmonar agudo (DPA) inducido por LPS en ratones. La composición del lote de D-005 fue: ácido láurico (35.8%), oleico (28.4%), mirístico (14.2%), palmítico (8.9%), esteárico (3.3%), cáprico (1.9%), caprílico (1.2%) y palmitoleico (0.05%), con un contenido total de ácidos grasos de 93.7%. D-005 (200 mg/kg) redujo significativamente el edema pulmonar (EP) (≈ 28% de inhibición) y la relación peso pulmón/peso corporal (PP/PC) (75.8% de inhibición). D-005 (25, 50, 100 y 200 mg/kg) produjo una reducción significativa de la puntuación histológica (59.9, 56.1, 53.5 y 73.3% de inhibición, respectivamente). La dexametasona, fármaco de referencia, fue efectiva en este modelo experimental. En conclusión, el pretratamiento con dosis orales únicas de D-005 previno significativamente el DPA inducido por LPS en ratones.

Inhibition of cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) by D-005 (A lipid extract of Acrocomia crispa fruits) / [Inhibición de la ciclooxigenasa (COX) y la 5-lipooxigenasa (5-LOX) por el D-005 (extracto lipidico del fruto de la Acrocomia crispa)

This study was aimed to investigate whether the a lipid extract from Acrocomia crispa fruits (D-005) inhibits COX and 5-LOX enzyme activities in vitro. This study demonstrates that D-005 inhibits markedly and in a dose dependent manner COX-2 and 5-LOX activities. The dual inhibition of COX-2 and 5-LOX supports further research on the potential anti-inflammatory effect of D-005.

El objetivo de este estudio fue investigar si el extracto lipídico de los frutos de Acrocomia crispa (D-005) inhibe in vitro las actividades de las enzimas COX y 5-LOX. Este estudio demuestra que el D-005 inhibe marcadamente y de manera dosis dependiente las actividades de la COX-2 y 5-LOX. La inhibición dual de la COX-2 y 5-LOX soportan futuras investigaciones sobre el potencial efecto anti-inflamatorio del D-005.

La empatia y los estudiantes de medicina en la Universidad de Azuay, Ecuador / Empathy and medical students at the University of Azuay, Ecuador

Resumen Objetivo: Identificar el nivel de empatia en los estudiantes de medicina de la Universidad del Azuay. Materiales y métodos: Se realizó un estudio transversal. Los niveles de empatía de los estudiantes se midieron a través de la Escala de Empatia Médica de Jefferson, versión S (EEMJ) en español, adaptada culturalmente en el contexto de Ecuador. La comparación de los datos se realizó mediante análisis de varianza bifactorial modelo III. Resultados: Se pudo observar que las mujeres tienen un promedio mayor en los niveles de empatía que los hombres en casi todos los cursos, excepto en el sexto. Existieron diferencias estadísticamente significativas cuando se analizaron por separado las puntuaciones por género y curso; estas diferencias no fueron significativas cuando se analizó la interacción entre las dos variables señaladas. Conclusiones: Los resultados de este estudio son consistentes con otros trabajos, especialmente con los realizados en Latinoamérica, que muestran variabilidad de la respuesta empática en estudiantes de medicina.

Abstract Objective. To assess the level of empathy in medical students attending University of Azuay. Materials and methods. A cross-sectional study was conducted. Empathy levels were measured through Jefferson's Physician Empathy Scale, S (JPES) Spanish version, culturally adapted to the Ecuadorian context. A two-factor analysis of variance model III was used in order to assess differences between groups. Results. Female students scored higher average levels of empathy when compared to male students in almost all courses except the sixth. Statistically significant differences were found only when gender and class scores were separately analyzed. These differences were non-significant when the interaction between the two mentioned variables was analyzed. Conclusions. The results of this study are consistent with other studies, especially those conducted in Latin America, which show variability of empathic response among medical students.

D-002 (beeswax alcohols): concurrent joint health benefits and gastroprotection.

Nonsteroidal antiinflammatory drugs include the traditional drugs and more selective COX-2 inhibitors. Traditional nonsteroidal antiinflammatory drug use is hampered by their gastrotoxicity, while COX-2-inhibitors increase the cardiovascular risk. The search of safer substances for managing inflammatory conditions is updated, a challenge wherein dual COX/5-LOX inhibitors have a place. This review summarizes the benefits of D-002, a mixture of higher aliphatic beeswax alcohols, on joint health and gastric mucosa. D-002 elicits gastroprotection through a multiple mechanism that involves the increased secretion and improved quality of the gastric mucus, the reduction of hydroxyl radical, lipid peroxidation, protein oxidation, neutrophil infiltration and the increase of antioxidant enzymes on the gastric mucosa. Consistently, D-002 inhibits NSAIDs, ethanol, pylorus-ligation and acetic acid-induced gastric ulceration in rats, and has reduced gastrointestinal symptoms in clinical studies. Early results found that D-002 was effective in the cotton pellet-induced granuloma and carrageenan-induced pleurisy model in rats, lowering pleural leukotriene B4 levels without causing gastrointestinal ulceration. However, D-002 effects on inflammation received little attention for years. Recent data have shown that D-002 inhibited both COX and 5-LOX activities with a greater affinity for 5-LOX and could act as a dual COX/5-LOX inhibitor. This mechanism might explain efficacy in experimental inflammatory and osteoarthritic models as well as clinical efficacy in osteoarthritic patients while supporting the lack of D-002 gastrotoxicity, but not the gastroprotective effects, which appear to be due to multiple mechanisms. In summary oral D-002 intake could help manage inflammatory conditions that impair joint health, while offering gastroprotection.

D-004 ameliorates phenylephrine-induced urodynamic changes and increased prostate and bladder oxidative stress in rats.

BACKGROUND: Lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) mainly depend on alpha1-adrenoreceptors (α1-ADR) stimulation, but a link with oxidative stress (OS) is also involved. D-004, a lipid extract of Roystonea regia fruits, antagonizes ADR-induced responses and produces antioxidant effects. The objective of this study was to investigate whether D-004 produce antioxidant effects in rats with phenylephrine (PHE)-induced urodynamic changes. METHODS: Rats were randomized into eight groups (ten rats/group): a negative vehicle control and seven groups injected with PHE: a positive control, three treated with D-004 (200, 400 and 800 mg/kg) and three others with tamsulosin (0.4 mg/kg), grape seed extract (GSE) (250 mg/kg) and vitamin E (VE) (250 mg/kg), respectively. RESULTS: Effects on urinary total volume (UTV), volume voided per micturition (VM), malondialdehyde (MDA) and carbonyl groups (CG) concentrations in prostate and bladder homogenates were study outcomes. While VM and UTV lowered significantly in the positive control as compared to the negative control group, the opposite occurred with prostate and bladder MDA and CG values. D-004 (200-800 mg/kg) increased significantly both VM and UTV, lowered significantly MDA in prostate and bladder homogenates, and reduced GC levels only in the prostate. Tamsulosin increased significantly VM and UTV, but unchanged oxidative variables. GSE and VE unchanged the UTV, whereas VE, not GSE, modestly but significantly attenuated the PHE-induced decrease of VM. CONCLUSIONS: Single oral administration of D-004 (200-800 mg/kg) was the only treatment that ameliorated the urodynamic changes and reduced increased oxidative variables in the prostate of rats with PHE-induced prostate hyperplasia.

Protective effects of D-002 on experimentally induced gastroesophageal reflux in rats.

AIM: To investigate the effects of beeswax alcohols (D-002) on the esophageal damage induced by gastroesophageal reflux (GER) in rats. METHODS: Sixty male rats were randomized into six groups (10 rats/group): a negative control and five groups with experimentally induced GER: a positive vehicle control, three treated with D-002 (25, 100 and 200 mg/kg, respectively), and one with omeprazole 10 mg/kg. All treatments were given by gastric gavage. One hour after dosing, GER was produced by simultaneous ligation of the pyloric end and the forestomach. Esophageal lesions index (ELI), gastric secretion volume and acidity, and esophageal malondialdehyde (MDA) and sulfhydryl (SH) group concentrations were measured. Statistical significance was considered at P < 0.05. RESULTS: As compared to the negative control, the positive control group exhibited increased ELI (5.2 ± 0.33 vs 0 ± 0, P = 0.0003), gastric secretion volume (2.69 ± 0.09 vs 0.1 ± 0.0, P = 0.0003) and acidity (238 ± 19.37 vs 120.0 ± 5.77, P = 0.001), and esophageal concentrations of MDA (2.56 ± 0.1 vs 1.76 ± 0.28, P = 0.001) and SH groups (1.02 ± 0.05 vs 0.56 ± 0.08, P = 0.0003). D-002 (25, 100 and 200 mg/kg) reduced ELI (3.36 ± 0.31, 2.90 ± 0.46 and 2.8 ± 0.23, respectively) vs the positive control (5.2 ± 0.33) (P = 0.004; P = 0.002; P = 0.001, respectively). There were no significant changes in acidity with D-002 treatment, and only the highest dose reduced the volume of the gastric secretion (1.92 ± 0.25) vs the positive control (2.69 ± 0.09, P = 0.013). D-002 (25, 100 and 200 mg/kg) lowered the esophageal MDA (2.05 ± 0.16, 1.98 ± 0.22 and 1.93 ± 0.22, respectively) (P = 0.01; P = 0.03; P = 0.03, respectively) and SH group concentration (0.87 ± 0.06, 0.79 ± 0.08 and 0.77 ± 0.06, respectively) (P = 0.04; P = 0.04; P = 0.02) vs the positive control (2.56 ± 0.10 and 1.02 ± 0.05, respectively). Omeprazole decreased ELI (2.54 ± 0.47), gastric secretion volume (1.97 ± 0.14) and acidity (158.5 ± 22.79), esophageal MDA (1.87 ± 0.13) and SH group (0.72 ± 0.05) concentrations vs the positive control (P = 0.002; P = 0.001; P = 0.02; P = 0.003; P = 0.002, respectively). CONCLUSION: Acute oral administration of D-002 decreased macroscopic esophageal lesions and oxidative stress in rats with experimentally induced GER, without modifying gastric secretion acidity.

Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action.

D-002, a mixture of higher aliphatic beeswax alcohols, produces gastroprotective and antioxidant effects. To investigate the gastroprotective effect of D-002 against indomethacin-induced ulcers, oxidative variables and myeloperoxidase (MPO) activity in the rat gastric mucosa were examined. Rats were randomized into six groups: a negative vehicle control and five indomethacin (50 mg/kg) treated groups, comprising a positive control, three groups treated orally with D-002 (5, 25 and 100 mg/kg) and one group with omeprazole 20 mg/kg intraperitoneally (ip). The contents of malondialdehyde (MDA), protein carbonyl groups (PCG), hydroxyl radical generation and catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and MPO enzyme activities in the rat gastric mucosa were assessed. Indomethacin increased the content of MDA and PCG, the generation of *OH radical and MPO enzyme activity, while it decreased the CAT, GSH-PX and SOD activities as compared to the negative controls. D-002 (5-100 mg/kg) significantly and dose-dependently reduced indomethacin-induced ulceration to 75 %. Also, D-002 decreased the content of MDA and PCG, the generation of hydroxyl radicals and MPO activity as compared to the positive controls. The highest dose of D-002 (100 mg/kg) increased significantly GSH-PX and SOD activities, while all doses used increased CAT activities. Omeprazole 20 mg/kg, the reference drug, reduced significantly the ulcers (93 %), MDA and PCG, the generation of hydroxyl radicals and MPO activity, and increased the CAT, GSH-PX and SOD activities. D-002 treatment produced gastroprotective effects against indomethacin-induced gastric ulceration, which can be related to the reduction of hydroxyl radical generation, lipid peroxidation, protein oxidation and MPO activity, and to the increase of the antioxidant enzymes activities in the rat gastric mucosa.

Evaluation of anti-inflammatory and antinociceptive effects of D-002 (beeswax alcohols).

D-002, a mixture of six higher aliphatic alcohols purified from beeswax, displayed anti-inflammatory effects in carrageenan-induced pleurisy and cotton pellet granuloma in rats. The aim of the present study was to confirm the anti-inflammatory properties of D-002 and to explore its potential analgesic effects. Xylene-induced mouse ear oedema was used to assess the anti-inflammatory effect, acetic acid-induced writhing and hot plate responses for the analgesic activity, and the open field and horizontal rotarod tests for motor performance. For anti-inflammatory tests, mice were randomised into a negative vehicle control and five xylene-treated groups: the vehicle, D-002 (25, 50 and 200 mg/kg) and indomethacin 1 mg/kg (reference drug). Treatments were given for 15 days. Effects on oedema formation and myeloperoxidase (MPO) activity were tested. For analgesia and motor performance tests, mice were randomised into a vehicle control and D-002-treated groups (25, 50 and 200 mg/kg). Two sets of experiments were done, which included acute and repeat (15 days) dosing. D-002 (25, 50 and 200 mg/kg) significantly decreased xylene-induced ear oedema (44.7, 60.8 and 76.4%, respectively) and the increase of MPO activity induced by xylene (38.0, 47.0 and 57.0%, respectively), while indomethacin significantly inhibited xylene-induced oedema (59.9%) and MPO activity (57.5%). Single and repeat doses of D-002 (25, 50 and 200 mg/kg) decreased the acetic acid-induced writhing responses by 21.2, 28.2 and 40.1%, for the single doses; 25.2, 35.1 and 43.2%, respectively, for the repeat doses, but did not affect the hot plate, open field and rotarod behaviours. Aspirin 100 mg/kg significantly decreased acetic acid-induced abdominal constrictions and morphine (5 mg/kg) significantly increased the latency of the hot plate response. This study confirmed the anti-inflammatory effects of D-002 and demonstrated its analgesic effects on the acetic acid-induced writhing, but not on the hot plate response, which suggests that the antinociceptive effects of D-002 could be related to its anti-inflammatory activity.

Efectos del D-003 sobre el perfil lipídico y la agregación plaquetaria en pacientes con diabetes tipo 2 / Effects of D-003 on lipid profile and platelet aggregation of type 2 diabetic patients

Los eventos coronarios constituyen la primera causa de muerte en sujetos con diabetes mellitus tipo 2. Un incremento en la agregación plaquetaria y altos niveles de colesterol asociado a la lipoproteína de baja densidad (C-LDL) contribuyen al riesgo coronario en diabéticos. El D-003, una mezcla de ácidos grasos obtenida de la caña de azúcar, ha mostrado reducir la agregación plaquetaria y los niveles séricos de C-LDL en sujetos normo e hipercolesterolémicos. Este estudio a doble ciego, controlado con placebo, investigó los efectos del D-003 sobre la agregación plaquetaria y el perfil lipídico en 50 diabéticos tipo 2, los que fueron aleatorizados para recibir después de un periodo inicial, D-003 (10 mg/día) o placebo por 10 semanas. Todos los sujetos completaron el estudio. El D-003 redujo significativamente la agregación plaquetaria inducida por ácido araquidónico (52,9%) y por colágeno (54,4%) y los niveles séricos de C-LDL (26,7%), colesterol total (CT) (19,6%) y triglicéridos (23,9%), mientras que incrementó el C-HDL (12,4%) en relación a los niveles básales y al grupo placebo. El D-003 fue seguro y bien tolerado. Se concluye que el D-003 redujo significativamente la agregación plaquetaria y los niveles séricos de C-LDL en pacientes con diabetes tipo 2, pero otros estudios deben confirmar estos resultados.

Coronan/ events are the leading cause of death in subjects with type 2 diabetes, and increased platelet aggregation and serum low-density lipoprotein-cholesterol (C-LDL) contribute to coronary risk in diabetes patients. D-003, a mixture of sugarcane wax acids, has shown to reduce platelet aggregation and serum C-LDL in normocholesterolemic and hypercholesterolemic subjects. This doubleblinded, placebo-controlled study investigated the effects of D-003 on platelet aggregation and lipid profile in 50 type 2 diabetes patients who were randomized, after a baseline phase, to D-003 (10 mg/d) or placebo for 10 weeks. Al I the subjects completed the study. D-003 significantly lowered arachidonic acid- (52.9%) and collagen-induced (54.4%) platelet aggregation, C-LDL (26-7%), total cholesterol (TC) (19.6%) and triglycerides (23.9%), while increased high-density lipoprotein-cholesterol (C-HDL) (12.4%) vs baseline and placebo. D-003 was safe and well tolerated. To conclude with, D-003 significantly reduced platelet aggregation and serum C-LDL in type 2 diabetes, but further studies should confirm these results.

D-004, a lipid extract from royal palm fruit, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice.

D-004, a lipid extract of Roystonea regia fruits, has been shown to reduce Testosterone, but not dihydrotestosterone-induced prostate hyperplasia in rodents. Inhibition of prostate 5?-reductase seems to explain these effects of D-004. Finasteride, an inhibitor of 5?-reductase used to treat benign prostate hyperplasia (BPH), has been shown to produce drug-induced depression and to increase mouse immobility in the forced swim test (FST). In this study, therefore, we investigated the effect of D-004 on the immobility in the FST and the tail suspension test (TST) in mice. Also, its effects on other behavioural tests (grip strength, open field activity and rotarod test) were investigated. Mice were randomized into five groups: three groups orally treated with D-004 (250, 500 and 1000 mg/kg) or vehicle (control group), and a fifth group that received intraperitoneally (IP) imipramine 20 mg/kg for 30 days. In the FST, D-004 (250, 500 and 1000 mg/kg) produced a statistically significant reduction in immobility (51, 58, and 65%, respectively, versus the control group), whereas imipramine reduced FST immobility by 69%. In the TST, D-004 (250 and 500 mg/kg) significantly, but modestly (21%) reduced the immobility versus the control group, although less than imipramine (50%). The lowest dose of D-004 (50 mg/kg), however, was ineffective. D-004 did not alter the results of other behavioural tests. In conclusion, D-004 (250-1000 mg/kg) administered orally for 30 days reduced the immobility in the FST and the TST in mice, and had no effect on other behavioural tests in mice.

Antioxidant effects of D-004, a lipid extract from the Roystonea regia fruit, on the plasma of healthy men

The aim of this study was to conduct a randomized, double-blind and placebo-controlled study to investigate the effects of D-004, a lipid extract of the Roystonea regia fruit that prevents testosterone- and phenylepinephrine-induced prostate hyperplasia in rodents, on plasma oxidative markers in healthy men. We enrolled male volunteers (20–55 years) in good health and without lower urinary tract symptoms. Thirty-four eligible participants were randomized to placebo or D-004 (320 mg) capsules administered daily for 6 weeks. An interim check-up and a final visit were conducted after 3 and 6 weeks of therapy, respectively. Physical examinations were performed at each visit, and laboratory tests were performed at baseline and at treatment completion. Oxidative variables included plasma malondialdehyde (MDA), total hydroxyperoxides (TOH), sulphydryl (SH) groups and total antioxidant status (TAS). We assessed treatment compliance and addressed adverse experiences (AEs) at weeks 3 and 6. At week 6, with D-004, the mean reductions of plasma MDA (26.7 percent), TOH (18.8 percent) and SH groups (31.6 percent), and the mean increase of TAS (35.3 percent) were significantly different from those of placebo (P < 0.001 for plasma TAS, P < 0.0001 for all other comparisons). D-004 did not differ from the placebo in safety indicators. There were two withdrawals (both in the D-004 group), with one due to dyspepsia (the only AE during the trial). In conclusion, D-004 displayed antioxidant effects on plasma oxidative markers in healthy men, which was consistent with findings from laboratory experimental studies(AU)

Antioxidant effects of D-004, a lipid extract from the Roystonea regia fruit, on the plasma of healthy men.

The aim of this study was to conduct a randomized, double-blind and placebo-controlled study to investigate the effects of D-004, a lipid extract of the Roystonea regia fruit that prevents testosterone- and phenylepinephrine-induced prostate hyperplasia in rodents, on plasma oxidative markers in healthy men. We enrolled male volunteers (20-55 years) in good health and without lower urinary tract symptoms. Thirty-four eligible participants were randomized to placebo or D-004 (320 mg) capsules administered daily for 6 weeks. An interim check-up and a final visit were conducted after 3 and 6 weeks of therapy, respectively. Physical examinations were performed at each visit, and laboratory tests were performed at baseline and at treatment completion. Oxidative variables included plasma malondialdehyde (MDA), total hydroxyperoxides (TOH), sulphydryl (SH) groups and total antioxidant status (TAS). We assessed treatment compliance and addressed adverse experiences (AEs) at weeks 3 and 6. At week 6, with D-004, the mean reductions of plasma MDA (26.7%), TOH (18.8%) and SH groups (31.6%), and the mean increase of TAS (35.3%) were significantly different from those of placebo (P<0.001 for plasma TAS, P<0.0001 for all other comparisons). D-004 did not differ from the placebo in safety indicators. There were two withdrawals (both in the D-004 group), with one due to dyspepsia (the only AE during the trial). In conclusion, D-004 displayed antioxidant effects on plasma oxidative markers in healthy men, which was consistent with findings from laboratory experimental studies.

Effects of D-003, a mixture of sugarcane wax acids, on platelet aggregation in hypercholesterolemic patients. A dose-titration, randomised, placebo-controlled trial.

Increased platelet aggregation contributes to vascular risk. D-003, a mixture of high molecular weight sugarcane wax acids, has shown antiplatelet effects in experimental models and healthy volunteers. This randomised, double-blinded, placebo-controlled study investigated the effects of titrated doses of D-003 (5-20 mg/d) on platelet aggregation in hypercholesterolemic patients. After a 4-week baseline phase, 56 patients were randomised to D-003 5 mg/d or placebo. The doses were doubled every 15 days if arachidonic acid (AA)-induced platelet aggregation was not inhibited at least by 15%. AA (0.75 and 1.5 mmol/L) and collagen (1 microg/mL)-induced platelet aggregation, laboratory and physical safety indicators were assessed at baseline and every 15 days thereafter, when adverse events (AE) were also reported. No significant change of platelet aggregation was found in the placebo group. After 15, 30 and 45 on therapy, D-003 reduced platelet aggregation induced with both AA 0.75 mmol/L (18.1%, 19.0% and 30.3%, respectively) and AA 1.5 mmol/L (17.0%, 16.3% and 22.5%, respectively), and also collagen-induced platelet aggregation (26.6%, 20.8% and 29.4%) (p < 0.01 at days 15 and 30 versus placebo, p < 0.0001 at study completion). The mean inhibition of platelet aggregation with D-003 at day 15, at which all patients had received the lowest dose, was over 15%. Nineteen out of 28 D-003 randomised patients (67.9%) required dose titration to achieve such goal. At trial completion, the mean estimated dose was 11.6 mg/d. D-003 lowered low-density lipoprotein (22.0 %), total cholesterol (14.7%) and raised high-density lipoprotein-cholesterol (10.9%) (p < 0.0001 versus placebo). Six patients (2 placebo, 4 D-003) withdrew from the trial, none due to AE. D-003 did not modify the safety indicators with respect to placebo. Four patients (2 placebo, 2 D-003-treated) reported AE: pruritus and increased blood pressure (2 placebo) and rash and polyphagla (2 D-003). In conclusion, D-003 (5-20 mg/d) given as doses titrated every 15 days (5-20 mg/d) inhibited AA- and collagen-induced platelet aggregation in hypercholesterolemic patients and was well tolerated.

Ex vivo antioxidant effects of D-004, a lipid extract from Roystonea regia fruits, on rat prostate tissue

To investigate whether oral treatment with D-004, a lipid extract of the Cuban royal palm fruit, produces antioxidant effects in the prostate tissue of normal and testosterone (T)-treated rats. Methods: In our first experiment, normal rats were distributed into five groups: one group treated with the vehicle and four groups treated with D-004 (100, 200, 400 or 800 mg/kg). In our second experiment, rats were randomized into five groups: a negative control group and four T-injected groups. The latter were comprised of a positive control group treated with the vehicle, and three groups treated with D-004 (200, 400 or 800 mg/kg). Results: In normal rats, D-004 (100_800 mg/kg) inhibited significantly and dose-dependently iron-initiated malondialdehyde (MDA) accumulation in prostate homogenates (35.7 percent_80.0 percent ) vs. the controls. D-004 (200_800 mg/kg) significantly reduced baseline MDA and carbonyl groups in prostate homogenates of normal rats to approximately 80 percent and 50 percent, respectively, and totally (100 percent) in T-treated rats. Conclusion: Oral treatment with D-004 reduced MDA and carbonyl groups dose-dependently and markedly in normal and T-injected rats. These findings show that D-004 given at doses effective to prevent prostate hyperplasia also produces antioxidant effects in the prostate tissue. (Asian J Androl 2008 Jul; 10: 659_666)(AU)

Effects of D-003, a mixture of very long chain saturated fatty acids, and policosanol on in vivo lipid peroxidation in rats.

BACKGROUND: D-003 and policosanol (CAS 557-61-9), specific and distinct mixtures of high molecular weight primary aliphatic acids and alcohols, respectively, have shown to inhibit lipid peroxidation in vivo, but comparative studies between their effects on lipid peroxidation processes had not been conducted before. OBJECTIVE: To compare the effects of D-003 and policosanol on markers of lipid peroxidation in vivo in rats. METHODS: Male Wistar rats were distributed into 9 groups: a control group treated with acacia gum/water vehicle, 4 with policosanol and 4 with D-003, both treatments at 5, 25, 100 and 250 mg/kg. Treatments were administered during 4 weeks. RESULTS: Both treatments significantly and dose-dependently reduced plasma malondyaldehide (MDA) and total peroxides. Nevertheless, while D-003 was effective from 5 mg/kg, the lowest effective dose of policosanol was 25 mg/kg. The maximal effects of both treatments were obtained with 100 mg/kg, but greater in D-003 than in policosanol group, and the same occurred across all doses tested. MDA concentrations generated with the enzymatic system in liver homogenates were also significantly and dose-dependently inhibited with both treatments. The lowest effective doses of D-003 and policosanol were 5 and 100 mg/kg, respectively, and the highest inhibitions of about 80% (D-003) and 11% (policosanol). D-003 was more effective than policosanol in all comparisons. D-003 was also more effective than policosanol for lowering MDA concentrations generated with the no enzymatic system, but in these conditions policosanol was effective from 25 mg/kg and produced an inhibition somewhat greater (about 29%) than on MDA-generated by the enzymatic system. Both policosanol and D-003 did not modify the activity of endogenous antioxidant enzymes compared with the controls. CONCLUSIONS: D-003 (5-250 mg/kg) orally administered for 4 weeks was more effective than policosanol for lowering all the lipid peroxidation markers assessed, like plasma MDA and total peroxides, and MDA concentrations generated by the enzymatic and non-enzymatic oxidant systems of liver homogenates. The inhibitions with D-003 were marked and dose-dependent. Neither D-003 nor policosanol modified the activity of enzymes involved in the endogenic antioxidant defensive system.