Fiebre de origen desconocido con diagnóstico médico-forense / Fever of unknown origin with forensic medical diagnosis

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Validation of an HPLC-DAD method for the determination of plant phenolics

Abstract A selective, sensitive and precise reversed phase HPLC-DAD method was developed and validated for the simultaneous determination of six phenolic acids in the aqueous extract and their hydrolyzed forms prepared from Solanum elaeagnifolium Cav., Solanaceae, Ampelocissus acapulcensis (Kunth) Planch., Vitaceae, or Brosimum alicastrum Sw., Moraceae. The new method showed good linearity (r > 0.999) in a relatively wide concentration range (0.5-100 mg/l). The limits of detection and quantification for the compounds were in the range of 0.097-0.467 mg/l and 0.097-0.496 mg/l, respectively. The recoveries of compounds were calculated in three different concentrations in the range of 88.07-109.17% and matrix effect was less than 5% for all phenolic acids. Finally, our developed HPLC method is simple, reliable and successfully applied to identify and quantify the phenolic acids in complex aqueous extracts from medicinal species, that can be useful for the analysis of infusions that people consume in folk medicine.

Prenatal vitamin D status and respiratory and allergic outcomes in childhood: A meta-analysis of observational studies.

BACKGROUND: Prenatal vitamin D status may influence offspring's respiratory and allergic outcomes; however, evidence is inconclusive. A systematic review and meta-analysis were conducted on the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or cord blood at birth with the risk of offspring's respiratory and allergic conditions. METHODS: Two independent researchers conducted systematic searches for observational studies published until May 2017 using defined keywords on vitamin D and health outcomes, including respiratory tract infections (RTIs), wheeze, asthma, atopic eczema, allergic rhinitis, allergic sensitization, and lung function. Random-effects meta-analyses were conducted. RESULTS: A total of 34 from 547 retrieved articles were included. Increased prenatal exposure to 25(OH)D was inversely associated with risk of RTIs. Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratio was 0.64 (95% CI 0.47, 0.87). A positive borderline association was found for lung function at school age (FEV1 z-score coefficient 0.07, 95% CI -0.01, 0.15). No associations were found for wheeze, asthma, atopic eczema, allergic rhinitis, and allergic sensitization. CONCLUSION: The introduction of public health measures to tackle vitamin D status in pregnancy may reduce the burden of RTIs in offspring. Current evidence does not support an impact on asthma and allergy.

Factors associated with the time to the first wheezing episode in infants: a cross-sectional study from the International Study of Wheezing in Infants (EISL).

Male gender, asthmatic heredity, perinatal tobacco smoke exposure and respiratory infections have been associated with wheeze in the first years of life, among other risk factors. However, information about what factors modify the time to the first episode of wheeze in infants is lacking. The present study analyses which factors are associated with shorter time to the first episode of wheeze in infants. Parents of 11- to 24-month-old children were surveyed when attending their health-care centres for a control visit. They answered a questionnaire including the age in months when a first wheeze episode (if any) had occurred (outcome variable). The study was performed in 14 centres in Latin America (LA) and in 8 centres in Europe (EU) (at least 1,000 infants per centre). Factors known to be associated with wheezing in the cohort were included in a survival analysis (Cox proportional hazards model). Summary hazard ratios adjusted for all risk factors (aHR) were calculated using the meta-analysis approach with random effects. A total of 15,067 infants had experienced wheezing at least once, out of 35,049 surveyed. Male gender in LA (aHR 1.05, 95% confidence interval (CI) 1.00-1.10, P=0.047), parental asthma in LA and EU (aHR 1.05, 95% CI 1.00-1.11, P=0.037), infant eczema in EU (aHR 1.25, 95% CI 1.12-1.39, P<0.001) and having a cold during the first 3 months in LA and EU (aHR 1.97, 95% CI 1.90-2.04, P<0.001), in LA (aHR 1.98, 95% CI 1.90-2.06, P<0.001) and in EU (aHR 1.91, 95% CI 1.75-2.09, P<0.001) were associated with a shorter period of time to the first episode. Breast feeding for at least 3 months was associated with a longer period, only in LA (aHR 0.91, 95% CI 0.86-0.96, P<0.001). Cold symptoms during the first 3 months is the most consistent factor shortening the time to the first episode of wheezing; breast feeding for ⩾3 months delays it only in LA, whereas eczema shortens it only in EU. Avoiding a common cold in the first months of life could be a good strategy to delay the first wheeze episode; however, cohort studies will help to elucidate this association.

Aparato genital femenino en el nuevo baremo / Female genital tract in the new medical scale

La nueva tabla 2.A.1, Baremo médico, clasificación y valoración de secuelas, recoge importantes modificaciones. Dentro de las que corresponden al Aparato genital femenino, Capítulo VIII, nos encontramos con que disponen de una ubicación específica para el sistema reproductor. Por otra parte, el arco de valoración se amplía en lo que se refiere a la región vulvo-vaginal, y se incluye una nueva secuela con relación a la función ovárica en la mujer posmenopáusica (AU)

The new table 2.A.1, medical Scale, classification and valuation of sequels, contains important modifications. Within the corresponding female genital, Chapter VIII, we find that have a specific location for the reproductive system. Moreover, the arc expands valuation in regard to the vulvo-vaginal region, and includes a new sequel regarding ovarian function in postmenopausal women (AU)

Comparative Study of Lead Concentration in Feathers of Urban and Rural Passerines in Merida, Mexico.

Lead is a commonly monitored heavy metal because of potential health effects on exposed organisms. We quantified lead in secondary feathers of two passerine bird species, clay-colored thrushes (Turdus grayi) and great-tailed grackles (Quiscalus mexicanus), from an urban and a rural site in the municipality of Merida, Yucatan. Urban lead concentration was significantly higher than its rural counterpart for both species (p < 0.05). In the urban site, lead concentration was similar in both species (p = 0.14). However, data from the rural site showed that lead concentration was significantly higher in thrush feathers (p < 0.05). Lead levels herein presented are among the lowest ever reported suggesting that either lead accumulation or absorption is limited. Finally, our data seem to support the hypothesis that species feeding ecology plays a major role in lead accumulation.

Vitamin D and Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease that affects a high number of children worldwide. It is mainly caused by a disruption of the epidermal barrier and an abnormal immune response. Vitamin D might have some effects on the innate and adaptive immune system, generally in favour of decreasing allergenic mechanisms, as well as it might improve the skin barrier and decrease the risk of skin colonization. Thus, an increasing body of evidence links this vitamin to atopic dermatitis, although conclusions are not unanimous. Many observational studies have shown that low vitamin D serum levels are associated with a higher prevalence of this epidermal disease in childhood, but others have not. Differences in exposure time, vitamin D dose, age of participants, etc. could explain these conflicting results. Moreover, no study has been performed to date in order to determine whether variations in vitamin D levels at different ages differentially influence the risk of atopic dermatitis. A number of randomized controlled trials have tested the usefulness of systemic vitamin D as a treatment for this condition, but the results are also inconclusive. Nevertheless, topical vitamin D is not recommended because it can worsen skin lesions. Narrowband ultraviolet B is used to treat atopic dermatitis, although there is little evidence relating this type of phototherapy with variations of serum vitamin D levels or to what extent phototherapy benefits are mediated through vitamin D.

Specificity and sensitivity of objective tests to detect possible malingering in fibromyalgia: a case-control study in 211 Spanish patients.

OBJECTIVES: To characterise patients diagnosed with fibromyalgia (FM) who present a clinical profile suggestive of simulation. METHODS: Observational case-control study of 218 patients who met the classification criteria for FM. The profile supporting simulation was based on the proposed criteria for evaluating disability related to the simulation of pain. RESULTS: Compared with controls (n=105), patients with suspected simulation of FM (n=106) had a higher mean age (52.5 vs. 49.2 years, p=0.003), a higher frequency of primary education (88.7% vs. 58.1%; p<0.001), a higher percentage of separated/widowed persons (33.9% vs. 8.6%, p<0.001), a higher frequency of psychiatric disorders (100% vs. 67.6%, p<0.001), a higher mean number of positive 'control' tender points (4.5 vs. 1.3, p<0.001), a higher mean FIQ questionnaire score (89.8 vs. 68.8, p<0.001) and a lower mean LHS questionnaire score (41.0 vs. 59.9, p<0.001). Patients with suspected simulation were able to walk a shorter distance in the 6-minute walk test than controls (231.0 vs. 356.3 metres, p<0.001), while the appearance of allodynia was achieved with a significantly lower mmHg pressure (159.8 vs. 229.9 mm Hg, p<0.001). CONCLUSIONS: Some physical/functional tests, together with the administration of specific questionnaires, may identify a subgroup of patients with FM with a profile consistent with simulation or malingering; these patients have a differentiated demographic and psychiatric profile in comparison with FM patients without a profile of simulation.

[Ectopic sebaceous glands in the esophagus. Report of three cases]. / Glándulas sebáceas ectópicas en esófago. Reporte de tres casos.

Sebaceous glands typically are located in the pilosebaceous unit located in the superficial layers of the skin. Thus, ectopic sebaceous glands in the esophagus are a very unusual condition. Since 1962 when De la Pava and Pickren described that sebaceous glands could be ectopically located in the esophagus, no more than 30 cases have been reported in the literature. Macroscopically, single or multiple nodular yellowish lesions are found, and most of the times are overlooked. In this paper, we describe 3 cases (2 female and one male) of ectopic sebaceous glands in the esophagus incidentally detected during routine upper gastrointestinal tract endoscopic examination. Histopathology diagnoses were supported using immunohistochemestry for AE1/AE3 citokeratins and epithelial membrane antigen.

Glándulas sebáceas ectópicas en esófago. Reporte de tres casos / Ectopic sebaceous glands in the esophagus. Report of three cases

Resumen La presencia de glándulas sebáceas en el esófago constituye una entidad poco frecuente, debido a que estas normalmente se encuentran en la unidad pilosebácea de la piel. Macroscópicamente se observan como lesiones nodulares amarillentas, únicas o múltiples y que a veces pasan inadvertidas. En este trabajo describimos 3 casos (2 mujeres y un hombre) con localización ectópica de glándulas sebáceas en el esófago detectadas de forma incidental durante la realización de estudios endoscópicos del tracto digestivo superior. En todos los casos el diagnóstico histopatológico se confirmó mediante inmunohistoquímica para citoqueratinas AE1/AE3 y antígeno de membrana epitelial. (AU)

AbstractSebaceous glands typically are located in the pilosebaceous unit located in the superficial layers of the skin. Thus, ectopic sebaceous glands in the esophagus are a very unusual condition. Since 1962 when De la Pava and Pickren described that sebaceous glands could be ectopically located in the esophagus, no more than 30 cases have been reported in the literature. Macroscopically, single or multiple nodular yellowish lesions are found, and most of the times are overlooked. In this paper, we describe 3 cases (2 female and one male) of ectopic sebaceous glands in the esophagus incidentally detected during routine upper gastrointestinal tract endoscopic examination. Histopathology diagnoses were supported using immunohistochemestry for AE1/AE3 citokeratins and epithelial membrane antigen (AU)

Tumor contralateral de testículo, debut a los 10 años de evaluación oncológica / Contralateral tumor of the testis, an onset at ten (10) years of oncological assessment

Joven masculino, de la raza negra, de 41 años de edad, que en el año 1999, acude a consulta de urología del Hospital General "Abel Santamaría Cuadrado" por un aumento de volumen del testículo izquierdo, no doloroso con diagnóstico clínico e imaginológico de tumor testicular izquierdo, es ingresado en el servicio de Urología, realizándole el tratamiento quirúrgico (orquiectomia izquierda ) constatándose el resultado biópsico que reporta seminoma clásico, clasificado (T1N1M0), asociando radioterapia y quimioterapia una evolución satisfactoria. El paciente es seguido en las consultas periódicas multidisciplinarías oncourológicas, en el 2009, 10 años después refiere dolor en testículo derecho, aumento de volumen en la porción media e inferior, que se interpreta de inicio como una orquiepididimitis, recibiendo un tratamiento con antibióticos (ciprofloxacina, amoxicilina ) sin respuesta al tratamiento. Los exámenes imageneológicos USG; TAC reportan imágenes nodulares con densidades variables en relación con proceso inflamatorio o tumoral y escasas adenopatías retroperitoniales e inguinales bilaterales la mayor 13mm, por lo que se decide realizar BAFF testicular derecho, comprobándose la existencia de células malignas. Se realiza la orquiectomia derecha, con el diagnóstico histopatológico seminoma testicular clásico T1NOMO-S0 (Etapa Clínica 1A). La evolución post operatoria es satisfactoria, se indica suplemento androgénico y radioterapia 30Gy. Actualmente asintomático.

A 41 years-old, black, male patient who in 1999 attended to the urology office at "Abel Santamaria Cuadrado" University Hospital with an increase of volume in the left testis, non-painful having the clinical and imaging diagnose of left testicular tumor, the patient was admitted in the Urology Service to undergo surgical treatment (left orchiectomy), verifying by biopsy, a classic seminoma, which was classified as T1N1MO. Radiotherapy and chemotherapy was indicated showing a satisfactory progress. The patient was followed-up in periodic multidisciplinary, onco-urologic consultations. In 2009, 10 years after, the patient complained of pain in the right testis, increase of volume in the middle-inferior portion of the testis that was interpreted as a process of epididymo-orchitis, starting with antibiotics (ciprofloxacin, amoxicillin),where no-treatment response was observed. Imaging examinations showed nodular imagines with variable densities in relation to an inflammatory or tumoral process and limited retro-perineal and inguinal-bilateral adenopathies <13mm, performing a BAAF in the right testis which verified the existence of malignant cells, a right orchiectomy was carried out, pathologic findings showed a classic testicular seminoma T1NOMO-S0 (Clinical stage 1A). Post operative progress is satisfactory, indicating the treatment of androgenic supplements and y-radiotherapy (30Gy). Currently the patient is asymptomatic.

Tumor contralateral de testículo, debut a los 10 años de evaluación oncológica / Contralateral tumor of the testis, an onset at ten (10) years of oncological assessment: a case report

Joven masculino, de la raza negra, de 41 años de edad, que en el año 1999, acude a consulta de urología del Hospital General Abel Santamaría Cuadrado por un aumento de volumen del testículo izquierdo, no doloroso con diagnóstico clínico e imaginológico de tumor testicular izquierdo, es ingresado en el servicio de Urología, realizándole el tratamiento quirúrgico (orquiectomia izquierda ) constatándose el resultado biópsico que reporta seminoma clásico, clasificado (T1N1M0), asociando radioterapia y quimioterapia una evolución satisfactoria. El paciente es seguido en las consultas periódicas multidisciplinarías oncourológicas, en el 2009, 10 años después refiere dolor en testículo derecho, aumento de volumen en la porción media e inferior, que se interpreta de inicio como una orquiepididimitis, recibiendo un tratamiento con antibióticos (ciprofloxacina, amoxicilina ) sin respuesta al tratamiento. Los exámenes imageneológicos USG; TAC reportan imágenes nodulares con densidades variables en relación con proceso inflamatorio o tumoral y escasas adenopatías retroperitoniales e inguinales bilaterales la mayor 13mm, por lo que se decide realizar BAFF testicular derecho, comprobándose la existencia de células malignas. Se realiza la orquiectomia derecha, con el diagnóstico histopatológico seminoma testicular clásico T1NOMO-S0 (Etapa Clínica 1A). La evolución post operatoria es satisfactoria, se indica suplemento androgénico y radioterapia 30Gy. Actualmente asintomático...(AU)

A 41 years-old, black, male patient who in 1999 attended to the urology office at Abel Santamaria Cuadrado University Hospital with an increase of volume in the left testis, non-painful having the clinical and imaging diagnose of left testicular tumor, the patient was admitted in the Urology Service to undergo surgical treatment (left orchiectomy), verifying by biopsy, a classic seminoma, which was classified as T1N1MO. Radiotherapy and chemotherapy was indicated showing a satisfactory progress. The patient was followed-up in periodic multidisciplinary, onco-urologic consultations. In 2009, 10 years after, the patient complained of pain in the right testis, increase of volume in the middle-inferior portion of the testis that was interpreted as a process of epididymo-orchitis, starting with antibiotics (ciprofloxacin, amoxicillin),where no-treatment response was observed. Imaging examinations showed nodular imagines with variable densities in relation to an inflammatory or tumoral process and limited retro-perineal and inguinal-bilateral adenopathies <13mm, performing a BAAF in the right testis which verified the existence of malignant cells, a right orchiectomy was carried out, pathologic findings showed a classic testicular seminoma T1NOMO-S0 (Clinical stage 1A). Post operative progress is satisfactory, indicating the treatment of androgenic supplements and y-radiotherapy (30Gy). Currently the patient is asymptomatic...(AU)

Las buenas prácticas clínicas: su aplicación en el dato primario para los eventos adversos / Good clinical practices and its use in primary data in adverse events

Las Buenas Prácticas Clínicas son estándares nacionales e internacionales con que se realizan los Ensayos Clínicos. El ejercicio de dichas prácticas ofrece credibilidad y confiabilidad a los datos aportados por la etapa de desarrollo clínico del producto en investigación; respecto a los derechos e integridad del paciente y guían al trabajador de la salud. El Evento Adverso tiene que ser recogido en el documento primario con todas sus características y transcrito al Cuaderno de Recogida de Datos de cada sujeto en investigación. Durante el l Ensayo Clínico, el sujeto en estudio puede presentar síntomas o signos desfavorables con o sin relación causal con el producto. Se revisaron nueve Historias Clínicas y sus respectivos Cuadernos de Recogida de Datos de los pacientes portadores de cáncer de próstata hormona-refractario, incluidos en el Ensayo Clínico Fase II Evaluación clínica del uso del esquema vacuna-quimioterapia-vacuna con la vacuna de Factor de Crecimiento Epidérmico en el tratamiento de estos pacientes, tratados en el sitio de investigación Hospital III Congreso de Pinar del Río. Se usaron métodos estadísticos de análisis. Los eventos adversos más frecuentes resultaron las alteraciones en los exámenes de laboratorio clínicos en un 100 por cinto de los pacientes, seguidos de los digestivos 88,9 por ciento del total de pacientes. Hubo un 94 por ciento de correspondencia en la trascripción del dato del evento adverso al cuaderno de recogida de datos; un 94,1 por ciento de los eventos fueron clasificados adecuadamente y un 92,2 por ciento transcritos correctamente en el CRD. El 100 por ciento de los eventos adversos tuvo un criterio de percepción. Recomendamos monitoreos internos periódicos a cada EC del sitio...(AU)

The good clinical practices are national or international standards for the clinical assays; these practices give credibility and confidence to data given by the stage of the clinical development of the product to be investigated. The adverse event has to be compiled in the primary document with all the characteristics and transcribed to the notebook of data in every subject in the investigation. During the I Clinical Assay, the subject may have symptoms or unfavourable signs with causal relationship with the product or not. Nine clinical records as well as its respective notebooks for data in carriers of the hormone-refractory prosthatic cancer included in the Fase II Clinical assay Clinical evaluation of the use of the vaccine –chemotherapy –vaccine using the epidermic growing factor in the treatment of these patients were treated in III Congreso Pinar del Rio hospital. Statistical analysis methods were used. The most frequent adverse events were: changes in the clinical laboratory tests (100 per cent), followed by 94 per cent of correspondence in the transcription data of the adverse event into the notebook of data; 94,1 per cent of the events were properly classified and a 92,2 per cent were transcribed properly in the CDR (Revolution Defence Committee).100 per cent of the adverse events had a perception criterion. It is recommended periodical internal monitoring in every CA of the site...(AU)

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)

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.

Nursing research and the prevention of infectious diseases among vulnerable populations.

Racial and ethnic minorities, women and infants, youth, and other special needs populations have been found to be disproportionately affected by infectious disease morbidity and mortality, particularly Human Immunodeficiency Syndrome/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other sexually transmitted diseases (STDs). Being a vital component of the health care delivery system, nurses play an important role in improving the health of these vulnerable populations. Twenty-six studies reporting results from evaluations of prevention strategies targeting HIV/AIDS and other STDs among vulnerable populations were reviewed. The more effective interventions appeared to be those that tailored their program content to the specific risk factors of their target population and included skills training in their curriculum. Although nurses have contributed significantly in understanding the risk factors of vulnerable groups in the United States through cross-sectional research studies, more research is needed in the evaluation of intervention programs that use this knowledge to develop and implement prevention programs, particularly at a population-based level.

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.

Primary care cancer control interventions including Latinos: a review.

BACKGROUND: Even though 86% of adult Latinos have a usual source of care, there is a paucity of literature on primary care-based interventions to promote cancer prevention and control in this population. This systematic review examines published primary care-based cancer control interventions that included Latinos. METHODS: MEDLINE, the Cochrane Registry, and EMBASE were searched from January 1985 to January 2003. Any primary care-based intervention using a controlled trial, quasi-experimental, or pre-post design that targeted breast, cervical, or colorectal cancer was included if at least 5% of the sample was Latino. RESULTS: A total of 14 intervention studies met inclusion criteria. Seven of the 14 studies described patient or provider reminder interventions. Other interventions incorporated into the primary care setting one of the following: community health educators, culturally sensitive videos, audit with feedback, materials from the "Put Prevention Into Practice" campaign, and vouchers for free screenings. The heterogeneity of designs and outcome variables and the low number of Latinos presented obstacles to combining data to estimate the overall effectiveness of primary care interventions for this population. Qualitatively, patient and physician reminders and management systems strategies including audit with feedback for providers appear to result in improved screening utilization. CONCLUSIONS: There is a paucity of data on the effectiveness of primary care cancer control interventions directed at Latinos. Primary care-based interventions that have been effective in non-Latinos could incorporate culturally appropriate elements and lessons from community-based research and could be applied to Latinos so that their effectiveness can be assessed in this group.

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.