[Abordaje y atención a la cronicidad con tecnologías digitales en las políticas sanitarias en España]. / Approach and attention to chronicity with digital technologies in health policies in Spain.

OBJECTIVE: From the healthcare policies that support Public Health strategies, technology implementation in healthcare is an innovative element to address chronicity. Its introduction is not uniform across Spain, despite of the existence of digital strategic implementation and national chronicity plans. The aim of this paper was to explore the current deployment of autonomic strategies for chronicity and the implementation of digital tools for telemonitoring and user support. METHODS: A descriptive cross-sectional study was conducted through documental review of autonomous strategies in digital health and chronicity care, available until 2020. Consequently, a consultation was carried out to eighteen experts addressing autonomic availability, benefits and barriers to healthcare digitalization. RESULTS: The expert consultation revealed that, in fifteen autonomous communities, the use and the enhancement of digital technologies were addressed and in nine the focus was on promoting digital transformation. Eleven communities are working on updates, fourteen have health-related digital applications, thirteen allow users checking their test results, ten allow them to carry out administrative procedures, nine deliver patient support resources, and three provide telematic communication channels. 38.89% of the consulted refered not knowing about the existence of any follow-up and monitoring programs in their community. The 60% identified a gap in digital competencies among citizens and the lack of resources, as main barriers to implementation. CONCLUSIONS: There exists disparity in the update of strategies to address chronicity and the introduction of digital technologies. Many of them are currently updating, which is an opportunity to provide efficient responses that incorporate digital tools.

OBJECTIVE: La implementación de tecnologías digitales supone un elemento innovador para el abordaje de la cronicidad, como parte de las estrategias de Salud Pública. Su implantación es variable a nivel autonómico, pese a existir un plan nacional. Este trabajo pretendió conocer el despliegue de las estrategias autonómicas sobre cronicidad, así como de la implementación de opciones de telemonitorización y apoyo al usuario. METHODS: Se realizó un estudio descriptivo transversal mediante revisión documental de las estrategias autonómicas de salud digital y abordaje de la cronicidad disponibles hasta 2020. Se realizó una posterior consulta a dieciocho personas expertas sobre disponibilidad autonómica, beneficios y barreras a la digitalización de la atención sanitaria. RESULTS: La consulta a personas expertas reveló que quince comunidades autónomas abordaron el uso y la potenciación de tecnologías digitales y nueve trabajaron en favorecer la trasformación digital. Once comunidades trabajan en actualizaciones, catorce tienen aplicaciones digitales de salud, trece permiten a los ciudadanos consultar resultados de pruebas, diez permiten trámites administrativos, nueve ofrecen recursos de apoyo al paciente y tres disponen de canales telemáticos de comunicación. El 38,89% de los consultados refirió no conocer los programas de seguimiento y monitorización en su comunidad. El 60% identificó a la falta de competencias digitales de la ciudadanía y a la falta de recursos como barreras de su implantación. CONCLUSIONS: Existe disparidad en la actualización de estrategias para el abordaje de la cronicidad y la implantación de tecnologías digitales. Muchas de ellas se están actualizando, lo que supone una oportunidad para dar respuestas eficientes que incorporen las herramientas digitales.

Potential anti neuro-inflammatory effect of BioCen-128 in animal models of dementia.

BACKGROUND: BioCen-128 is a new active pharmaceutical ingredient composed of a specific bovine thymic fraction of a polypeptide nature. Positive results of similar thymus extracts have been shown to be effective in delaying the processes associated with aging, immunosenescence and Alzheimer's disease (AD), where the inflammation plays an important role. Because of the anti-inflammatory potential of BioCen-128, the aim of this study was to evaluate the granuloma model induced by a cotton wool implantation and the model induced by intracerebroventricular (ICV) administration of streptozotocin (STZ). METHOD: The experiment was carried out using male OF-1cenp mice weighing 20 ± 2 g. RESULTS: Mice administered BioCen-128 in via the IP route at 5, 10 and 20 mg/kg of corporal weigh showed a decrease in the wet and dry weights of the granuloma, providing evidence of a systemic anti-inflammatory effect. In the ICV model of STZ, the administration of BioCen-128 improved cognitive function. CONCLUSION: These responses suggested an anti-neuroinflammatory effect explainable by the action of thymosin ß4 and thymosin alfa proteins. The results suggested that BioCen-128 could be used in the prevention and treatment of some diseases, for example AD, where neuroinflammation is one of the biological events that take place.

Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B.

BACKGROUND: Acid-sensing ion channels (ASICs) have a significant role in the sensation of pain and constitute an important target for the search of new antinociceptive drugs. In this work we studied the antinociceptive properties of the BM-21 extract, obtained from the sea grass Thalassia testudinum, in chemical and thermal models of nociception in mice. The action of the BM-21 extract and the major phenolic component isolated from this extract, a sulphated flavone glycoside named thalassiolin B, was studied in the chemical nociception test and in the ASIC currents of the dorsal root ganglion (DRG) neurons obtained from Wistar rats. RESULTS: Behavioral antinociceptive experiments were made on male OF-1 mice. Single oral administration of BM-21 produced a significant inhibition of chemical nociception caused by acetic acid and formalin (specifically during its second phase), and increased the reaction time in the hot plate test. Thalassiolin B reduced the licking behavior during both the phasic and tonic phases in the formalin test. It was also found that BM-21 and thalassiolin B selectively inhibited the fast desensitizing (τ < 400 ms) ASIC currents in DRG neurons obtained from Wistar rats, with a nonsignificant action on ASIC currents with a slow desensitizing time-course. The action of thalassiolin B shows no pH or voltage dependence nor is it modified by steady-state ASIC desensitization or voltage. The high concentration of thalassiolin B in the extract may account for the antinociceptive action of BM-21. CONCLUSIONS: To our knowledge, this is the first report of an ASIC-current inhibitor derived of a marine-plant extract, and in a phenolic compound. The antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs. That the active components of the extract are able to cross the blood-brain barrier gives them an additional advantage for future uses as tools to study pain mechanisms with a potential therapeutic application.

Repair of UVB-damaged skin by the antioxidant sulphated flavone glycoside thalassiolin B isolated from the marine plant Thalassia testudinum Banks ex König.

Daily topical application of the aqueous ethanolic extract of the marine sea grass, Thalassia testudinum, on mice skin exposed to UVB radiation resulted in a dose-dependent recovery of the skin macroscopic alterations over a 6-day period. Maximal effect (90%) occurred at a dose of 240 microg/cm(2), with no additional effects at higher doses. Bioassay-guided fractionation of the plant extract resulted in the isolation of thalassiolin B (1). Topical application of 1 (240 microg/cm(2)) markedly reduces skin UVB-induced damage. In addition, thalassiolin B scavenged 2,2-diphenyl-2-picrylhydrazyl radical with an EC(50) = 100 microg/ml. These results suggest that thalassiolin B is responsible for the skin-regenerating effects of the crude extract of T. testudinum.

Inhibition of human P450 enzymes by natural extracts used in traditional medicine.

Different medicinal plants are widely used in Cuba and Mexico to treat several disorders. This paper reports in vitro inhibitory effects on the P450 system of herbal products commonly used by people in Cuba and Mexico in traditional medicine for decades. Experiments were conducted in human liver microsomes. The catalytic activities of CYP1A1/2, 2D6, and 3A4 were measured using specific probe substrates. The Heliopsis longipes extract exhibited a concentration-dependent inhibition of the three enzymes, and similar effects were produced by affinin (an alkamide isolated from the H. longipes extract) and two catalytically reduced alkamides. Mangifera indica L. and Thalassia testudinum extracts, two natural polyphenol-rich extracts, diminished CYP1A1/2 and 3A4 activities, but not the CYP2D6 activity. These results suggest that these herbs inhibit the major human P450 enzymes involved in drug metabolism and could induce potential herbal-drug interactions.

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

AIM: 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%-80.0%) 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% and 50%, respectively, and totally (100%) 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.

Effects of D-003, a mixture of high-molecular-weight sugar cane wax acids, on lipid peroxidation markers in older individuals: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Aging is associated with increased lipid peroxidation (LP). D-003, a mixture of long-chain aliphatic primary acids purified from sugar cane wax, has been found to inhibit LP in experimental models and in healthy subjects. OBJECTIVES: The aim of this study was to assess the effects of D-003 on LP markers and the lipid profile of older individuals. METHODS: This randomized, double-blind, placebo-controlled study was conducted at the Plaza Veterans' House, Havana City, Cuba. Male and female patients aged ≥60 years with total cholesterol values of <6.1 mmol/L were eligible for inclusion in the study. After a 3-week lead-in and baseline assessment period, patients were randomized to receive PO D-003 5 mg/d, D-003 10 mg/d, or placebo for 8 weeks. The effect on copper-induced LP of low-density lipoprotein (LDL) particles was the primary variable, and the effects on plasma total antioxidant status (TAS), plasma malondialdehyde (MDA) concentration, plasma antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities, and the lipid profile were secondary variables. A clinical examination was performed at each visit (baseline, weeks 4 and 8). A clinical examination, LP, and blood tests (lipid profile, hematologic, and blood biochemistry safety indicators) were performed at baseline and after 8 weeks of treatment. Compliance and adverse events (AEs) were assessed at weeks 4 and 8. A 2-tailed P < 0.05 was considered statistically significant for comparisons of both continuous and categoric variables. RESULTS: Fifty-four patients aged ≥60 years were assessed for inclusion in the study, and 51 patients (40 women, 11 men; mean [SD] age, 67 [6] years) were included in the study. The lag phase of conjugated diene formation increased significantly and in a dose-dependent manner in the group treated with D-003 5 mg (24.7%; P < 0.01) and in the group treated with D-003 10 mg (29.3%; P < 0.01) compared with placebo. The maximal rate of conjugated diene propagation decreased significantly in the D-003 5- and 10-mg groups -22.7% and -25.8%, respectively; both, P < 0.05) compared with placebo. TAS increased significantly (17.7% and 23.0%, respectively; both, P < 0.01) in both active treatment groups compared with placebo. Plasma MDA concentration decreased significantly in the D-003 10-mg group (-28.6%; P < 0.05) but not in the D-003 5-mg group, compared with placebo. These changes were also significant compared with baseline. Antioxidant enzyme activities did not change in the active treatment groups compared with placebo or baseline. In the D-003 5- and 10-mg groups, significant decreases were found in LDL cholesterol concentration (-15.8% and -23.8%, respectively; both, P < 0.001) and total cholesterol concentration (-13.0% and -16.8%, both, P < 0.05) compared with placebo. High-density lipoprotein cholesterol concentration increased significantly in the D-003 5-mg group (5.7%; P < 0.05) and the D-003 10-mg group (18.2%; P < 0.001) compared with placebo. Changes in the lipid profile were also significant compared with baseline. In the placebo group, no variable changed significantly compared with baseline. D-003 was well tolerated at both dose levels, and no patient withdrew from the study. There were a total of 3 AEs reported: insomnia and acidity in 2 patients receiving placebo; and heartburn in 1 patient receiving D-003 5 mg. CONCLUSIONS: D-003 5 and 10 mg/d administered to these older individuals (aged ≥60 years) for 8 weeks inhibited LP of LDL and increased TAS in a dose-dependent manner, while plasma MDA concentration decreased in the patients receiving D-003 10 mg/d only. D-003 was well tolerated at both doses.

Age-Related Changes in the Behavior of Apolipoprotein E Knockout Mice.

The knockout mouse model, B6.129P2-Apoetm1Unc is homozygotic for the Apolipoprotein E (ApoE) deletion; thus, it is capable of developing hyperlipidemia and atherosclerosis but ApoE is also a lipid-transport protein abundantly expressed in most neurons in the central nervous system, so these animals could also be models of neurodegenerative diseases. The aim of this study was to determine age-related changes in spontaneous behavior and in learning and memory of Apolipoprotein E knockout mice. Spontaneous behavioral measurements included sleeping pattern, motor coordination and balance by rotarod and open field activity, whereas learning and memory tests included forced alternation in Y-maze, novel object recognition and passive avoidance conditioning. Significant behavioral differences between aged knockout mice and age-matched wild type strain, C57Bl/6 were found in all the behavioral tests, except for the rotarod test. Genetically' modified mice exhibited less huddling contact during sleeping, decreased locomotor activity in novel environments and in learning and memory deficits. These results are consistent with the cognitive impairment and memory loss seen as the earliest clinical symptoms in neurodegenerative disorders such as Alzheimer's disease. The ApoE knockout mice might therefore be an appropriate model for studying the underlying mechanisms involved in behavioral changes caused by neurodegenerative diseases as well as for evaluating new therapies for these pathologies.

A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO versus MIRCERA® and ior®EPOCIM.

CONTEXT: The recombinant human erythropoietin (rHuEPO) stimulates the erythropoiesis process. Because this glycoprotein has a short half-life, it needs to be administrated two to three times a week. One of the technics to solve this issue is the PEGgilation. AIMS: To evaluate the pharmacokinetics (PK) and pharmacodynamics of two new branched PEGylated erythropoietins (i.e., an asymmetric 32 kDa-PEG2-rHuEPO and a symmetric 40 kDa-PEG2-rHuEPO molecule) compared to non-PEGylated ior®EPOCIM and MIRCERA®. METHODS: Serum concentrations of both PEGylated and non-PEGylated erythropoietins were measured at various time points in order to determine PK parameters using non-compartmental analysis approach. The reticulocyte (%), erythrocyte count and hemoglobin levels were ascertained in order to compare the effect of these molecules after administrating a single intravenous dose (10 µg/kg) of each product in male New Zealand rabbits. RESULTS: Both branched PEGylated erythropoietin forms exhibited half-lives that were significantly longer than ior®EPOCIM (p<0.05), but not statistically different to MIRCERA®. The mean elimination half-life increased from 4 h (ior®EPOCIM) to 131 h for the 32 kDa-PEG2-rHuEPO and 119 h for the 40 kDa-PEG2-rHuEPO. Conversely, MIRCERA® exhibits a half-life of 64 h. Both PEGylated erythropoietin products significantly enhanced the stimulating effect on reticulocytes and erythrocytes formation, as well as on hemoglobin levels, when compared to ior®EPOCIM treatment up to 42 days post-dose. CONCLUSIONS: The PEGylation strategy employed in this study is an effective method to modify the pharmacokinetics and pharmacodynamics of rHuEPO molecule achieving higher half-lives and, therefore, longer in vivo bioactivity. Both of the branched PEGylated-EPO forms tested are promising candidates for human testing.

CONTEXTO: La eritropoyetina humana recombinante (rHuEPO) estimula la formación de eritrocitos en la medula ósea. Esta glicoproteína terapéutica presenta rápida eliminación en el organismo. Una de las estrategias tecnológicas para resolver esta problemática es la PEGgilación. OBJETIVOS: Evaluar la farmacocinética y la farmacodinámica de dos nuevas eritropoyetinas PEGiladas ramificadas (una asimétrica de 32 kDa-PEG2-rHuEPO y otra simétrica de 40 kDa-PEG2-rHuEPO) en comparación con ior®EPOCIM y el producto de referencia MIRCERA®. MÉTODOS: Se midieron las concentraciones séricas de eritropoyetina PEGilada y no PEGilada, a diferentes tiempos, para determinar los parámetros farmacocinéticos usando el método de análisis no compartimental. Se determinaron los % de reticulocitos, los niveles de eritrocitos y hemoglobina para comparar el efecto de estas moléculas después de administrar a dosis única 10 µg/kg por vía intravenosa en conejos Nueva Zelanda machos. RESULTADOS: Las eritropoyetinas PEGiladas ramificadas presentaron semividas significativamente superiores a ior®EPOCIM (p<0.05), pero no fueron estadísticamente diferentes a MIRCERA®. El t1/2 aumentó de 4 h (ior®EPOCIM) a 131 h para la 32 kDa-PEG2-rHuEPO y 119 h para la 40 kDa-PEG2-rHuEPO, respectivamente. Ambas eritropoyetinas PEGiladas mejoraron significativamente el efecto estimulante sobre la formación de reticulocitos y eritrocitos, así como los niveles de hemoglobina, en comparación con ior®EPOCIM hasta 42 días después de la dosis. CONCLUSIONES: La estrategia de PEGilación, empleada en este estudio, es un método efectivo para modificar la farmacocinética y farmacodinamia de moléculas de eritropoyetinas. Esta tecnología permitió aumentar la semivida de estas moléculas, así como prolongar su bioactividad in vivo. Ambas formas ramificadas de rHuEPO PEGiladas son candidatos prometedores para su uso clínico.

In vitro effect of D-004, a lipid extract of the fruit of the cuban royal palm (Roystonea regia), on prostate steroid 5α-reductase activity.

BACKGROUND: D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia), has been found to reduce prostatic hyperplasia (PH) induced with testosterone (T), but not PH induced with dihydrotestosterone (DHT), in rodents, suggesting the inhibition of prostate 5α-reductase activity. OBJECTIVES: The aims of this study were to assess whether D-004 inhibits prostate 5α-reductase activity in vitro and to examine the effects of D-004 on enzyme kinetics. METHODS: This experimental study was conducted at the Pharmacology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. Soluble rat prostate preparations were used as the source of 5α-reductase, and ((3)H)-DHT production was measured to determine prostate 5α-reductase activity. Cell-free rat prostate homogenates were pre-incubated with carboxymethyl cellulose 2% alone (control tubes) or D-004 (0.24-125 µg/mL) suspended in the vehicle (treated tubes) for 10 minutes prior to adding the labeled substrate ((3)H)-T Once the reaction was stopped, sterols were extracted with chloroform and aliquots were applied on silica gel plates developed in benzene-acetone (4:1, v/v). Areas containing DHT were scraped and radioactivity was counted. The median inhibitory concentration (IC50) was determined by measuring the conversion of T to DHT The apparent Michaelis-Menten constant (Km) and Vmax values before and after adding D-004 were determined in kinetic studies using labeled T (0.5-25 µmol/L). RESULTS: Compared with controls, D-004 significantly and dose-dependently inhibited the enzymatic reaction at doses of 1.95 to 125.0 µg/mL) (all, P < 0.05). The IC50 of D-004 required to inhibit 5a-reductase activity was 2.25 µg/mL. Enzyme inhibition was noncompetitive, since D-004 lowered the Vmax from 15.3 to 10.0 nmol DHT/min · mg(-1) protein, while the Km (4.54 µmol/L) was almost unaffected. CONCLUSIONS: D-004 dose-dependently and noncompetitively inhibited in vitro 5α-reductase activity in soluble fractions of rat prostate. Although the extent of the maximal inhibition was high and the value of IC50 was low, the relevance of such inhibition requires further study in vivo.

Plasma levels, tissue distribution, and excretion of radioactivity after single-dose administration of ((3)H)-oleic acid added to D-004, a lipid extract of the fruit of Roystonea regia, in rats.

BACKGROUND: D-004, a lipid extract of the fruit of Roystonea regia, contains a mixture of fatty acids-mainly oleic, lauric, palmitic, and myristic acids, with oleic acid being among the most abundant-that has been found to reduce the risk for prostatic hyperplasia (PH) induced with testosterone (T) in rats. The pharmacokinetic profile of D-004 has not been reported. OBJECTIVE: The objective of this study in rats was to assess plasma levels, tissue distribution, and excretion of total radioactivity (TR) after single-dose administration of oral D-004 radiolabeled with ((3)H)-oleic acid, as a surrogate for the pharmacokinetics of D-004. METHODS: This experimental study was conducted at the Pharmacology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. Single doses of suspensions of ((3)H)-oleic acid 0.16 µCi/mg mixed with D-004 400 mg/kg (radioactive dose/animal 7.2 µCi) were given orally to male Wistar rats weighing 150 to 200 g assigned to the treated or control group. Three rats were euthanized at each of the following times: 0.25, 0.5, 1, 1.5, 2, 4, 8, 24, 48, 72, 96, and 144 hours after study drug administration. After administration, the rats euthanized at the last experimental time point were housed individually in metabolism cages. Urine and feces samples were collected daily. At each time point, blood samples were drawn and plasma samples were obtained using centrifugation. After euthanization, tissue samples (liver, lungs, spleen, brain, kidneys, adipose tissue, muscle, stomach, small and large intestines, adrenal glands, heart, testes, prostate, and seminal vesicles) were quickly removed, washed, blotted, and homogenized. Plasma (100 µL), tissue aliquots (100 mg), feces (10 mg), and urine (100µL) were dissolved and TR was measured. Samples were assayed in duplicate. Results were expressed in µgEq of radio-labeled oleic acid per milliliter of plasma or urine or gram of tissue or feces. Plasma, tissue, feces, and urine samples of rats that did not receive ((3)H)-oleic acid were used as controls. Excretion was expressed as the percentage of the radioactivity excreted via each route with respect to the total radioactive dose administered to each rat. RESULTS: A total of 50 rats were included in the experiment (mean age, 4 weeks; mean weight, 310 g). Absorption was rapid; mean Cmax was 195.56 (31.12) µgEq/mL, and mean Tmax was 2 hours. Thereafter, a biphasic decay of TR was found: a rapid first phase (t1/2α, 1.33 hours), followed by a slower second elimination phase (t1/2ß, 36.07 hours). Radioactivity was rapidly and broadly distributed throughout the tissues, with more accumulating in the prostate than elsewhere. In the first 8 hours, accumulation of TR was greatest in the prostate, followed by the liver, small intestine, and plasma. Subsequently, TR increased in the small intestine, while it decreased in the liver and plasma. In contrast, over the periods of 24 and 144 hours after administration, TR increased in the adipose tissue, while it decreased in the other tissues and plasma. During those intervals, TR was greatest in the prostate, followed by adipose tissue. Mean peak radioactivity in the prostate (562.41 µgEq/g) was reached at 4 hours and decreased slowly thereafter. The prostate had the highest values of t1/2ß and cumulative AUC compared with the other tissues and plasma. Mean (SD) TR was similar in feces (33.48% [4.90%]) and urine (28.96% [5.32%]), with total excretion being 62.40% (5.90%) of the administered dose. CONCLUSIONS: In this experimental study, after single-dose administration of oral D-004 radiolabeled with ((3)H)-oleic acid in rats, TR was rapidly and widely distributed across the tissues, with the prostate having the highest accumulation of radioactivity. Excretion of TR was limited, with similar amounts being excreted in feces and urine. The broad distribution of radiolabeled oleic acid and/or its metabolites suggests (SD) pharmacokinetic rationale for the effectiveness of D-004 in reducing the risk for PH induced with T in rats.

Hamartomatosis biliar múltiple / Multiple biliary hamartomatosis

Introducción: La hamartomatosis biliar múltiple o también llamada enfermedad de los complejos de von Meyenburg fue descrita por este autor en 1955. Tiene un origen disembriogénico con un curso evolutivo benigno y asintomático, con pruebas funcionales hepáticas normales. Por los estudios de imágenes se puede confirmar el diagnóstico, pero igualmente ante un hígado multinodular pueden diagnosticar una hepatopatía crónica sin precisar su etiología, por lo que es imprescindible el diagnóstico histológico con biopsia hepática translaparoscópica dirigida. No se necesita ningún tratamiento específico y su seguimiento es ecográfico semestral o anual. Objetivo: Presentar el valor de la biopsia hepática dirigida por laparoscopia a las lesiones por hamartomatosis biliar múltiple. Desarrollo: Se presenta un paciente de 53 años con antecedentes de ser un bebedor social con frecuencia semanal. Ingresa por fiebre asociada a una sepsis urinaria, en el que aparece un fortuito hallazgo ecográfico de un hígado multinodular, sin precisar un diagnóstico etiológico por otros estudios de imágenes. Esto motivó a realizarle una laparoscopia con toma de biopsia hepática dirigida a las lesiones observadas. Se confirma el diagnóstico histológico de esta entidad. Conclusiones: Se demostró la importancia y vigencia del valor diagnóstico de la laparoscopia, al igual que la biopsia hepática dirigida para lograr el diagnóstico histológico de certeza en esta entidad(AU)

Introduction: Multiple biliary hamartomatosis or von Meyenburg complex disease was described by this author in 1955. Its origin is dysembryogenic with a benign and asymptomatic evolutionary course, with normal liver function tests. Imaging studies can confirm the diagnosis, but likewise, when it is a multinodular liver, chronic liver disease can be diagnosed without specifying its etiology, which is why it is essential a histological diagnosis with a directed overlaparoscopic liver biopsy. No specific treatment is needed and its follow-up is semi-annual or annual ultrasound. Objective: To present the value of laparoscopically directed liver biopsy for multiple biliary hamartomatosis lesions. Case report: A 53-year-old patient with a history of being a social drinker with a weekly frequency is reported. He was admitted for fever associated with urinary sepsis, in which a fortuitous ultrasound finding of a multinodular liver appeared, without requiring an etiological diagnosis by other imaging studies. This led to a laparoscopy with a liver biopsy aimed at the observed lesions. The histological diagnosis of this entity is confirmed. Conclusions: The importance and validity of the diagnostic value of laparoscopy, as well as directed liver biopsy to achieve a certain histological diagnosis in this entity, was demonstrated(AU)

Adenocarcinoma mucinoso uracal / Urachal mucinous adenocarcinoma

Introducción: El uraco o conducto onfalomesentérico es una estructura embrionaria que conecta el intestino medio y el saco vitelino, que involuciona antes del tercer trimestre de embarazo. Objetivo: Presentar un caso con diagnóstico de adenocarcinoma uracal, neoplasia maligna rara. Desarrollo: Paciente de 50 años de edad sin antecedentes patológicos, con cuadro clínico inicial de ascitis y dolor abdominal, al examen físico masa palpable en hipocondrio-fosa iliaca izquierda que en la tomografía abdominal se observa una masa adyacente a la cúpula vesical y pared anterior del abdomen. El resultado de la biopsia reportó un adenocarcinoma mucinoso del conducto onfalomesentérico (uracal). Al momento del diagnóstico, el paciente se encontró en un estadio IVB según el sistema Sheldon y otros y un IV según sistema Mayo, etapa avanzada de la enfermedad que determina mal pronóstico. Se instauró tratamiento con quimioterapia neoadyuvante, quirúrgico y continuación con quimioterapia adyuvante, el cual continúa, actualmente, con una evolución estable. Conclusiones: Esta es una neoplasia rara. Sospechar su diagnóstico llevará a un diagnóstico temprano, lo que mejorará el pronóstico y sobrevida de los pacientes afectados(AU)

Introduction: The urachus or omphalomesenteric duct is an embryonic structure connecting the midgut and the yolk sac, which regresses before the third trimester of pregnancy. Objective: To report a case with a diagnosis of urachal adenocarcinoma, a rare malignant neoplasm. Case report: A 50-year-old patient with no pathological history, who had an initial clinical condition of ascites and abdominal pain. At physical examination, we found a palpable mass in the left hypochondrium - iliac fossa, which revealed a mass next to the bladder dome and anterior wall on the abdominal tomography of the abdomen. The biopsy result reported a mucinous adenocarcinoma of the omphalomesenteric duct (urachal). At the time of diagnosis, the patient was in stage IVB according to the Sheldon et al system and IV according to the Mayo system, an advanced stage of the disease that determines poor prognosis. Treatment with neoadjuvant and surgical chemotherapy was established and adjuvant chemotherapy to follow, which currently continues with a stable evolution. Conclusions: This is a rare neoplasm. Suspecting its diagnosis will lead to an early diagnosis, which will improve the prognosis and survival of affected patients(AU)

Hemobilia como causa infrecuente y grave de hemorragia digestiva alta / Hemobilia as a rare and serious cause of upper gastrointestinal bleeding

Introducción: La hemobilia es por definición una causa de hemorragia digestiva alta, donde existe una comunicación de la vía biliar en cualquiera de sus segmentos con vasos sanguíneos que desembocan a través de la ampolla de Vater. Su presentación es infrecuente y no sospechada en la práctica clínica diaria de gastroenterólogos, cirujanos, hepatólogos, clínicos e intensivistas, con un difícil manejo diagnóstico-terapéutico y una elevada morbi-mortalidad. Objetivo: Describir tres casos de pacientes con diagnóstico de hemobilia. Desarrollo: Se presentan tres casos con hemobilia que tuvieron una elevada mortalidad y con diferente etiología; en el primer caso por trombosis de la arteria hepática postrasplante hepático, el segundo secundario a un colangiocarcinoma de la unión hepatocística y el tercero con diagnóstico de un aneurisma de la arteria hepática derecha confirmado y parcialmente tratado por angiotomografía, posteriormente intervenido quirúrgicamente y único sobreviviente. Conclusiones: Resultaron tres casos con hemobilia de diferentes causas, con una elevada mortalidad por la intensidad de la hemorragia digestiva alta y las comorbilidades asociadas, además de señalar que ninguno de ellos presentó la tríada clásica reportada por Quincke(AU)

Introduction: Hemobilia is, by definition, a cause of upper gastrointestinal bleeding, where there is a communication of the bile duct in any of its segments with blood vessels that flow through the ampulla of Vater. It is rare and it is not suspected in the daily clinical practice of gastroenterologists, surgeons, hepatologists, clinicians and intensivists, hence the diagnostic-therapeutic management is difficult and it has high morbidity and mortality. Objective: To report three cases of patients with a diagnosis of hemobilia. Case report: We report three cases of hemobilia of high mortality and different etiology. The first case had post-liver transplantation hepatic artery thrombosis, the second had asecondary cholangiocarcinoma of the hepatocystic junction and the third had diagnosis of confirmed right hepatic artery aneurysm partially treated by CT angiography, subsequently operated on and the only survivor. Conclusions: These three hemobilia cases had different causes, and high mortality due to the intensity of the upper gastrointestinal bleeding and the associated comorbidities, in addition to noting that none of them exhibited the classic triad reported by Quincke(AU)

Tareas docentes sobre educación ambiental en Enfermería, desde la educación en el trabajo / Teaching tasks on environmental education in Nursing from the education at work

RESUMEN Introducción: uno de los problemas profesionales a resolver por el egresado en Enfermería, es el enfrentamiento a riesgos y alteraciones higiénico-epidemiológicas relacionados con el medio ambiente. De ahí la necesidad de incidir en la educación ambiental desde la educación en el trabajo, por ser un área clave en la formación de este profesional. Objetivo: diseñar un sistema de tareas docentes sobre la educación ambiental en la carrera de Licenciatura en Enfermería, desde el área de educación en el trabajo. Materiales y métodos: se realizó una investigación descriptiva, de corte transversal, en la carrera de Licenciatura en Enfermería en la Facultad de Ciencias Médicas de Sagua la Grande, provincia Villa Clara, durante el curso 2019-2020. Se emplearon los métodos teóricos: analítico-sintético, inductivo-deductivo y sistémico-estructural. Métodos empíricos: análisis de documento, discusión grupal, observación y criterio de expertos. Se empleó la estadística descriptiva. Resultados: se constató que solo en el 50 % de las actividades de educación en el trabajo se ejecutan acciones sobre educación ambiental. En la entrevista, los profesores declararon tener dificultades para vincular los problemas ambientales en sus clases. Se aportó un sistema de tareas docentes dirigidas a la educación ambiental desde la educación en el trabajo, y las pautas para que cada docente pueda elaborar sus propias tareas en dependencia de las situaciones ambientales concretas de cada área de atención. Conclusiones: se desarrollaron ejemplos de tareas docentes para favorecer el aprendizaje de la educación ambiental en estudiantes de Licenciatura en Enfermería, a través de la educación en el trabajo (AU).

ABSTRACT Introduction: one of the professional problems to be solved by the graduated in Nursing is facing the risks and hygienic-epidemiological changes related to the environment. Therefore, the necessity of stressing environmental education from the education at work, because it is a key area in this professional training. Objective: to design a teaching tasks system on environmental education in the degree course of Nursing, from the field of the education at work. Materials and methods: a cross-sectional, descriptive research was carried out in the degree studies in Nursing in the Medical Sciences Faculty of Sagua la Grande "Lidia Doce Sanchez", Villa Clara province, during the 2019-2020 school year. The theoretical methods used were the analytic-synthetic, the inductive-deductive and the systemic-structural ones. The used empiric methods were documents' analysis, group discussion, observation and expert's criteria. Descriptive statistics was also used. Results: It was found that actions on environmental education are carried out only in 50 % of the education at work activities. In the interview, the teachers declared to have difficulties to link the environmental problems in their classes. A system of teaching task aimed at environmental education from the education at work and guidelines were provided so that each teacher can develop his or her own tasks depending on the concrete environmental situations of each area of care. Conclusions: examples of teaching tasks were developed to encourage the learning of environmental education in students of the degree course in Nursing, through the education at work (AU).

[Safety of reducing the recovery time after percutaneous and laparoscopic liver biopsy]. / Seguridad de la reducción del tiempo de reposo posbiopsia hepática percutánea y por vía laparoscópica.

BACKGROUND: Liver biopsy is the main diagnostic tool for the study of the liver, and as such, its inherent complications have been minimised as much as possible over the years, through the modification of several factors regarding its procedure, including post-biopsy recovery time. The aim of this study was to evaluate the safety in the reduction of post-liver biopsy recovery time. MATERIAL AND METHODS: A non-blinded, randomised clinical trial was conducted in the "Hermanos Ameijeiras" Hospital from November 2011 to October 2012, on 128 patients in order to assess safety when reducing post-biopsy recovery times. The patients were randomised into 2 groups. Group A was allowed a 6-hour recovery time, while Group B was allowed a 2-hour recovery time after liver biopsy. Complications were fully recorded. The Chi squared test of homogeneity and Student t test was used as appropriate, in the statistical analysis, a significance level of 0.05 was set. RESULTS: The main biopsy indication was elevated plasma transaminases. Pain in the puncture site was the most recurrent complication (67.2%), and the most serious complication was subcapsular liver haematoma in two cases (1.6%). There were no differences regarding the liver biopsy technique that could have caused complications in any group. CONCLUSIONS: There were no significant differences between 2 hours and 6 hours post-liver biopsy recovery time in terms of complications, so it is considered that after two hours the patient is incorporated more quickly into their activities, and the institution spends less material and human resources.

In vitro and in vivo study of octacosanol metabolism.

BACKGROUND: Policosanol is a mixture of very-long-chain aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects, whose main component is octacosanol. Scarce data about the metabolism of octacosanol and the other fatty alcohols composing policosanol have been published. METHODS: Human fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h. Lipid extracts were analyzed by thin layer chromatography, and the spots corresponding to octacosanol and octacosanoic acid were identified comparing with authentic standards. Spots were scraped, transferred to vials and radioactivity was measured. For corroborating the presence of octacosanol and octacosanoic acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vivo study of octacosanol metabolism was conducted in rats and Macaca arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and free octacosanol and octacosanoic acid were identified in liver and plasma by GC-MS at various time intervals. Monkeys were orally and endovenously treated with policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid and some chain-shortened FA was investigated. RESULTS: When fibroblasts were cultured in presence of (3)H-octacosanol, three spots were found: a first one corresponded to octacosanoic acid, a second to octacosanol and a third one remained unidentified. The radioactivity on the spot of octacosanoic acid slightly decreased throughout the incubation but increased in the third spot. Octacosanol and free octacosanoic acids were also identified in plasma of monkeys orally administered with policosanol. In addition, plasma samples showed free saturated acids, palmitic acid being the most abundant, followed by oleic and mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed. CONCLUSIONS: The present study demonstrates that octacosanoic acid is formed after incubation of fibroblast cultures with (3)H-octacosanol and after oral dosing with policosanol to rats. In addition, we demonstrated that shortened saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic) FA are also formed after oral dosing with policosanol to monkeys. The present results are consistent with the fact that octacosanol metabolism is linked to FA metabolism via beta-oxidation, but further studies need to explore the occurrence of more metabolites proving such hypothesis.

Six-month toxicity study of oral administration of D-003 in Sprague Dawley rats.

BACKGROUND: D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugarcane wax (Saccharum officinarum) having cholesterol-lowering and antiplatelet effects. AIM: This study was undertaken to investigate the toxicity induced by long-term oral administration of D-003 for 6 months to Sprague Dawley rats of both sexes. METHODS: Rats were randomly divided into four groups (20 rats of each sex/group): a control group. which received the vehicle, and three treatment groups, which received oral D-003 at doses of 250, 500 and 1000 mg/kg/day, respectively. Daily clinical observations and control of bodyweight and food consumption were conducted throughout the study period. On completion of active treatment, animals were sacrificed. Pharmacological effects associated with D-003 such as inhibition of platelet aggregation and increase in bleeding time were assessed in two satellite groups (14 animals of each sex/group): a control group and a group treated with the highest dose of D-003. Assessments of platelet aggregation to collagen were performed at baseline and at 6 months, and assessments of bleeding time were done at baseline, after 3 and 6 months of treatment, and after 30 days' washout. RESULTS: As expected, D-003 significantly inhibited platelet aggregation. Bleeding time was increased after 3 months of treatment with D-003; this increase was maintained at 6 months, and was reversible after washout. Coagulation factors such as prothrombin time and kaolin-activated thromboplastin-time, which were determined in eight male animals from each group, were unaffected by D-003. Data analyses of bodyweight gain, food consumption, clinical observations, blood biochemistry, haematology, organ weight ratios and histopathological findings did not show trends related to D-003 dose or significant differences between control and treated groups. CONCLUSION: It was concluded that the highest studied dose of D-003 (1,000 mg/kg/day) represented a non-toxic dose level in the present chronic toxicity study in rats.

Effects of d-003, a new hypocholesterolaemic and antiplatelet compound, on lipid profile and lipid peroxidation in healthy volunteers.

BACKGROUND: D-003 is a mixture of long-chain aliphatic primary acids purified from sugarcane wax with hypocholesterolaemic effects proven in rabbits and healthy volunteers; it lowers serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) and increases high-density lipoprotein-cholesterol (HDL-C). D-003 also prevents lipoprotein lipid peroxidation in experimental models. OBJECTIVE: To investigate the effects of D-003 on lipid profile and lipid peroxidation in healthy human volunteers. PARTICIPANTS: Forty-six healthy volunteers (24 women, 22 men). METHODS: This double-blind, randomised, placebo-controlled study investigated the effects of D-003 at 5 and 10 mg/day on the susceptibility of LDL to lipid peroxidation induced by copper ions in healthy volunteers. Forty-six individuals were randomised (1 : 2) to placebo or D-003 at 5 or 10 mg/day, the tablets being taken once a day with the evening meal for 8 weeks. Laboratory determinations and physical examination were performed at baseline and after 4 and 8 weeks of therapy, and compliance and adverse experience assessments were performed at weeks 4 and 8. RESULTS: All groups were well matched at baseline. At study completion, D-003 at 5 and 10 mg/day significantly (p < 0.001) lowered LDL-C, the primary response variable, by 20.8% and 28.8%, respectively. In addition, D-003 at 5 and 10 mg/day reduced (p < 0.001) TC (12.7% and 17.5%, respectively), LDL-C/ HDL-C (25.9% and 36.3%, respectively) and TC/HDL-C (18.6% and 26.3%, respectively), while significantly (p < 0.01) increasing HDL-C (7.7% and 12.4%, respectively). Triglycerides were significantly (p < 0.05) reduced (8.8% and 13.1%, respectively) with respect to baseline, but not versus placebo. Responses assessed at 4 weeks showed significant reductions of LDL-C, TC and atherogenic ratios with both doses of D-003, whereas HDL-C was significantly increased. Triglycerides, however, remained unchanged. No significant changes in any lipid profile variable occurred in the placebo group. D-003 at 5 and 10 mg/day significantly (p < 0.05) increased lag time (18.3% and 32.0%, respectively) and decreased maximum rate of diene propagation (V(max)) [12.7% and 19.1%, respectively] of copper-induced LDL peroxidation. D-003 5 and 10 mg/day attenuated the reduction of the reactivity against 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) by 19.9% and 32.0%, respectively. The treatment was well tolerated. Three subjects (one from each group) discontinued the study. Only one, treated with D-003 5 mg/day, discontinued because of an adverse event (gastritis). CONCLUSIONS: D-003 at 5 and 10 mg/day demonstrated dose-dependent cholesterol-lowering effects in healthy volunteers characterised by reductions in LDL-C, TC and atherogenic ratios, and increases in HDL-C. Effects on triglycerides were modest and uncertain. As expected from experimental studies, D-003 inhibited the susceptibility of LDL to lipid peroxidation assessed by three indicators lag time V(max) and reactivity versus TNBS. Further studies investigating the effect of larger doses and treatment duration must be conducted to confirm the reproducibility of the present results in different study populations.

Sistema de Superación en Manometría Esofágica para residentes y especialistas de Gastroenterología / Self-Improvement Systems about Esophageal Manometry for Gastroenterology Residents and Specialists

Introducción: La superación profesional, contribuye a la educación permanente del profesional para lograr su actualización, dirigido a la superación profesional de gastroenterólogos especialistas y residentes del Servicio de Gastroenterología Hospital Clínico Quirúrgico "Hermanos Ameijeiras" sobre la técnica de Manometría Esofágica. Objetivos: Diseñar un curso de superación para mejorar el conocimiento e interpretación de la Manometría Esofágica. Métodos: Se realizó un estudio de enfoque mixto, educativo, de desarrollo que culmina con el diseño del curso en Manometría Esofágica dirigido a residentes y especialistas en gastroenterología del Servicio de Gastroenterología del Hospital Hermanos Ameijeiras, para lo cual se trabajó con los diez residentes y siete especialistas del servicio, además de tres profesores consultantes de gran experiencia, considerados expertos. Se utilizó la encuesta para residentes y especialistas y entrevista en profundidad con los profesores consultantes. El método estadístico permitió presentación y análisis de los datos cuantitativos y el análisis de contenido para las entrevistas a los expertos. Se consideraron los aspectos éticos requeridos para la investigación, de la institución y los involucrados en el estudio. Resultados: El 100 por ciento de participantes, carecen de conocimientos y habilidades en el uso de la Manometría Esofágica. Se diseñó un curso básico- teórico que contribuirá a prepararlos para hacer diagnóstico, pronóstico y tratamiento en la Enfermedad por Reflujo Gastroesofágico, la Acalasia y otros trastornos motores del esófago. Conclusiones: Las necesidades de aprendizaje, de residentes y especialistas, justificaron el diseño del curso, contribuirá a superar a gastroenterólogos en el manejo de las afecciones mencionadas(AU)

Introduction: Professional improvement contributes to permanent professional education to achieve updated levels, aimed at the professional improvement of gastroenterologists, both residents and specialists, of the Gastroenterology Service of Hermanos Ameijeiras Clinical-Surgical Hospital regarding the technique of esophageal manometry. Objectives: To design an updating course for improving the knowledge and interpretation of esophageal manometry. Methods: A mixed, educational, and developmental study was carried out, which culminated in the design of the course in Esophageal Manometry for residents and specialists in gastroenterology of the Gastroenterology Service of Hermanos Ameijeiras Hospital, for which work was done with the ten residents and seven specialists of the service, as well as three experienced consultant professors, considered experts. We used the survey for residents and specialists and the in-depth interview with the consulting professors. The statistical method allowed the presentation and analysis of the quantitative data and the content analysis for the interviews with the experts. The ethical aspects required for the investigation were considered, from the institution and those involved in the study. Results: 100 percent of participants lacked knowledge and skills in the use of esophageal manometry. A basic theoretical course was designed to help prepare them for diagnosis, prognosis and treatment regarding gastroesophageal reflux disease, achalasia, and other motor disorders of the esophagus. Conclusions: The learning needs of residents and specialists justified the course design, and will help overcome gastroenterologists in the management of the aforementioned conditions(AU)