Effects of 17beta-estradiol on the cytotoxicity of etoposide in a lung carcinoma cell line and its bioavailability in ovariectomized Sprague-Dawley rats.

BACKGROUND: The activity of steroid hormones for the efficacy of antineoplastic drugs used in lung cancer treatment has not been explored. We evaluated the influence of 17beta-estradiol on the cytotoxicity of etoposide in a lung cancer cell line (A-549) and determined systemic levels of etoposide in vivoafter pretreatment with this hormone. METHODS: The effect of 17beta-estradiol alone and combined with etoposide on cellular proliferation was evaluated. Blood levels of etoposide were studied in ovariectomized female rats previously treated with 17beta-estradiol. Etoposide levels were determined by high-performance liquid chromatography, and a pharmacokinetic analysis was performed. RESULTS: 17beta-Estradiol showed a tendency towards an increase in cellular proliferation but did not change the cytotoxic effect of etoposide. This in vivo study demonstrated that the blood levels of etoposide significantly decreased in the 17beta-estradiol-treated group. CONCLUSION: The clear reduction in the in vivo systemic levels of etoposide in the presence of 17beta-estradiol suggests a possible role of this hormone in drug resistance. However, as these data cannot be extrapolated to clinic situations, more research is necessary to understand the interaction between hormonal compounds and antineoplastic drugs.

Optical portable instrument for the determination of CO2 in indoor environments.

A portable device based on a colorimetric sensor to determine the atmospheric level of CO2 gas is presented in this work. The system is based on a low-cost, low-power System on a Chip (SoC) microcontroller with integrated Wi-Fi. A user-friendly application was developed to monitor and log the CO2 measurements when the system is connected to a Wi-Fi network. The sensing membrane is directly deposited on the surface of the colour detector, thus reducing the complexity of the system. This sensing membrane is formed by a pH indicator α-naphtholphthalein, tetramethylammonium hydroxide pentahydrate, 1-ethyl-3-methylimidazolium tetrafluoroborate, Tween 20 and hydroxypropyl methylcellulose as the hydrophilic polymer. The system has been fully characterized, obtaining response and recovery times of 1.3 and 2.5 s, respectively, a limit of detection of 51 ppm, and an average resolution of 6.3 ppm. This portable device was applied for the in-situ determination of CO2 gas in the atmosphere inside classrooms in several secondary schools. The measurements were taken during complete workdays and the results were statistically compared with the same measurements taken using a commercially available non-dispersive infra-red (NDIR) device. No significant statistical differences were found between the results obtained using both devices. A complete statistical treatment of the measurements made with the proposed portable device was carried out. The obtained results show that the concentration of CO2 gas in some schools was higher than the desired concentration, with regard to influencing the student's health, safety, productivity and comfort. This demonstrates the need to control this parameter to ensure appropriate indoor environmental quality (IEQ).

Abordaje del síncope situacional en Atención Primaria. De la sospecha al diagnóstico / Approach to situational syncope in Primary Care. From the suspicion to the diagnosis

Se presenta el caso de un adolescente de 12 años con episodios repetidos de sensación de pérdida de conciencia inminente con recuperación posterior completa, mientras se prepara para ir al colegio. La anamnesis, exploración y pruebas complementarias serán clave para realizar el diagnóstico de exclusión y la posterior pauta de normas de conducta para su evitación (AU)

We report the case of a 12-year-old male patient with repeated episodes of sudden and transient loss of consciousness sensation with immediate recovery, while preparing himself for school. Anamnesis, exploration and complementary tests will be key elements for a diagnosis of exclusion and the subsequent set of guidelines for its avoidance (AU)

Histological evaluation of brain damage caused by crude quinolizidine alkaloid extracts from lupines.

The effects of the intracerebroventricular (ICV) administration of crude extracts of lupin quinolizidine alkaloids (LQAs) were studied in adult rat brain tissue. Mature L. exaltatus and L. montanus seeds were collected in western Mexico, and the LQAs from these seeds were extracted and analyzed by capillary gas chromatography. This LQA extract was administered to the right lateral ventricle of adult rats through a stainless steel cannula on five consecutive days. While control animals received 10 microl of sesame oil daily (vehicle), the experimental rats (10 per group) received 20 ng of LQA from either L. exaltatus or from L. montanus. All the animals were sacrificed 40 h after receiving the last dose of alkaloids, and their brains were removed, fixed and coronal paraffin sections were stained with haematoxylin and eosin. Immediately after the administration of LQA the animals began grooming and suffered tachycardia, tachypnea, piloerection, tail erection, muscular contractions, loss of equilibrium, excitation, and unsteady walk. In the brains of the animals treated with LQA damaged neurons were identified. The most frequent abnormalities observed in this brain tissue were "red neurons" with shrunken eosinophilic cytoplasm, strongly stained pyknotic nuclei, neuronal swelling, spongiform neuropil, "ghost cells" (hypochromasia), and abundant neuronophagic figures in numerous brain areas. While some alterations in neurons were observed in control tissues, unlike those found in the animals treated with LQA these were not significant. Thus, the histopathological changes observed can be principally attributed to the administration of sparteine and lupanine present in the alkaloid extracts.

A high-performance liquid chromatographic assay for determination of cisplatin in plasma, cancer cell, and tumor samples.

A method for determination of cis-diaminedichloroplatinum (II) (cisplatin) in ultrafiltered plasma, cell, and tumour samples is described. Cisplatin separation was carried out on a reversed-phase column using methanol-acetonitrile-water as the mobile phase. The flow rate was maintained constant at 1.6 mL/min and analysis was performed at 23 degrees C. Detection was carried out by absorbance at 254 nm. The method was linear in the range of 0.2-10 microg/mL, and the coefficients of variation were <10%. Using this technique, we measured the intracellular accumulation of cisplatin in cancer cells and in tumours of mice receiving treatment with cisplatin and evaluated the pharmacokinetics of cisplatin in nu/nu mice after intraperitoneal (i.p.) administration. The method proved to be adequate for measuring cisplatin both in vitro and in vivo and could be suitable for studies of cisplatin pharmacokinetics in animal models.

Effectiveness of surgery in liver metastasis from colorectal cancer: experience and results of a continuous improvement process.

PURPOSE: The aim of this study was to estimate the effectiveness of surgery in liver metastasis from colorectal cancer. METHODS: We conducted a prospective and observational study of patients with colorectal liver metastasis operated on at the San Cecilio University Hospital of Granada from March 2003 until June 2013. The primary variables of the result were survival and morbidity before 30 days of the post-operative period. We also measured preoperative and surgical variables. RESULTS: A total of 147 patients with liver metastasis of colorectal origin underwent surgical removal during the period of study, 38 of whom had repeat surgery. 34 had a second resection, 3 had a third one and one only patient had a fourth one, for a total of 185 registered operations. The global 5-year survival rate was 38 and 17 % after 10 years. There were 115 patients who had neither radiofrequency nor exploratory laparotomy, 38 % of them survived over 60 months. The average disease-free time was 23.6 months ± 47.3, with significant differences observed between types of procedures. Patients that were operated on just once (n = 25) had a five-year actuarial survival rate of 35 %, a morbidity rate of 24 % and a mortality rate of 0.6 % (1 patient only). The average hospital stay was 13.8 days and the disease-free time was 15.8 months. CONCLUSION: The results obtained in our surgical unit in terms of morbidity, mortality and five-year actuarial survival rates are comparable to those of other units at large institutions, which are currently considered the standards of quality.

Transitory expression of NADPH diaphorase (NOS) in axonal swellings after spinal cord injury.

To investigate the sites of nitric oxide synthase (NOS) expression after a spinal cord (SC) injury, NADPH-d diaphorase histochemistry was performed in the SC of adult rats sacrificed at different times from 1 h to 90 days after both SC contusion or transection. NOS could first be seen 12 h after injury in axonal swellings (AS) (club shaped structures at the tip of damage axons, associated with tissue destruction). NOS expression reached a maximum 3 days after injury, and gradually disappeared after 7 days. Finally, AS collapsed leaving behind microcysts. NOS expression and the consequent production of nitric oxide could be involved in the pathophysiology of the secondary damage, and/or could reflect a failed attempt for axonal regeneration.

Determination of HCV RNA concentration by direct quantitation of the products from a single RT-PCR.

A novel method for the estimation of HCV RNA levels in vivo was developed, based on competitive RT-PCR. The use of the Tth DNA polymerase and 5' 32P-labeled antisense primer respectively reduced cross-contamination and permitted the direct quantification of viral loads by the analysis of the radioactivity of PCR products derived from a clinical sample and a competitive deleted template, separated previously on a polyacrilamide gel. A HCV fragment (H) and a competitive (deltaH) RNA templates were synthesized for optimizing the method. The minimal starting RNA detectable by RT-PCR was 40 copies. RT-PCR performed with ratios deltaH/H ranging from 1/1 to 1/20 revealed different relative percentages of both H and deltaH products, changing from 90% of deltaH product when the ratio was 1/1 to 5%, when it was 1/20. Regression analysis was adjusted to a linear model and served to further estimate HCV RNA loads from clinical samples. HCV RNA quantitation was carried out in 19 patients. Higher viral loads were related to type 1b infection and persistence of HCV RNA after interferon therapy. This method is simple, reproducible and useful for rapid estimation of HCV RNA load in vivo.

Histochemical evidence of the increased expression of nicotinamide adenine dinucleotide phosphate-dependent diaphorase in neurons of the myenteric plexus after acute spinal cord injury in adult rats.

The expression of nitric oxide synthase in neurons of the gastrointestinal tract (GIT) after experimental spinal cord injury (SCI) was assessed in adult rats contused at T8. One day and 10 weeks after injury, specimens along the GIT were studied for NADPH-diaphorase histochemistry. A significant increase in the number of positive cell bodies and fibers in the myenteric plexus were observed 1 day after SCI, as compared to specimens from control and chronically injured rats, with the exception of the colon, which showed unchanged or decreased number of positive neurons in the acute and chronic stages, respectively. Positive neurons in the submucous plexus remained unchanged, excepting an increase in the colon after acute SCI, and a decrease in the duodenum in chronically injured rats. The altered nitric oxide neurotransmission in the GIT may be relevant to its reduced motility after SCI.

Bioavailability of diclofenac after intramuscular administration to rats with experimental spinal cord injury.

Spinal cord injury (SCI) has been proposed to reduce drug bioavailability after intramuscular administration owing to an impairment in blood flow to paralyzed limbs. To test this hypothesis, we studied diclofenac bioavailability after intramuscular administration in rats with SCI. Female Sprague-Dawley rats were submitted to SCI at the T8 level by contusion and received a 10-mg/kg intramuscular diclofenac dose in the thigh of the right hind limb 24 h after injury. Blood samples were drawn, diclofenac concentration was determined by high-performance liquid chromatography, and whole-blood concentration against time curves were constructed. SCI did not result in a significant change in C(max) and T(max), compared with sham-lesioned controls, suggesting that the rate of drug absorption was not altered. Half-life was prolonged, and therefore area under the curve was greater in SCI than in sham-lesioned animals. Therefore, 24 h after SCI at the T8 level, intramuscular diclofenac bioavailability was not impaired but was actually enhanced. Results suggest that the rate of intramuscular diclofenac absorption is not significantly altered, although its elimination is impaired, during the acute phase of SCI. It then appears that SCI-induced pharmacokinetic alterations are complex, the global bioavailability depending on the sum of SCI effects on absorption, distribution, and elimination. Systematic studies on SCI-induced alterations are thus required to provide information leading to a rational dosing regimen design for SCI patients.

Effect of experimental spinal cord injury on salicylate bioavailability after oral aspirin administration.

The purpose of the present work was to study whether spinal cord injury (SCI) alters salicylate bioavailability after oral aspirin administration. Female Sprague-Dawley rats were subjected to SCI at the T8 level by two procedures, contusion by the weight-drop method and severance by knife, and received a single oral aspirin dose (15 mg/kg) 24 h after injury. Blood samples were drawn and aspirin (ASA) and salicylic acid (SA) concentrations in whole blood were determined at selected times over a period of 240 min. Both SCI procedures produced similar alterations on salicylate bioavailability. ASA bioavailability was not significantly changed by SCI. On the other hand, SA peak concentrations were significantly reduced in 20% to 30%, compared with sham-lesioned controls. The area under the SA concentration against time curve was decreased in 10% to 25%, although this difference did not reach statistical significance. Results suggest that SCI at the T8 level decreases the rate, but not the extent, of aspirin absorption from the gastrointestinal tract. SCI-induced alterations in aspirin absorption appeared to be modest compared with those previously reported for other analgesic agents, such as paracetamol (acetaminophen).

Comparison between Sprague-Dawley and Wistar rats as an experimental model of pharmacokinetic alterations induced by spinal cord injury.

Two strains of rats, Sprague-Dawley and Wistar, were assayed in order to determine which strain is the more suitable experimental model for the study of pharmacokinetic alterations induced by spinal cord injury. Animals were submitted to spinal cord contusion at the T8-T9 level by the weight drop method. A single acetaminophen oral dose (100 mg/ kg) was administered 24 h after injury and blood samples were drawn for a period of 4 h. Acetaminophen concentration in whole blood was determined by high performance liquid chromatography and pharmacokinetic parameters were estimated. For both strains, Cmax and AUC were significantly lower, whereas tmax remained unchanged, in injured animals compared to sham-injured controls. Circulating acetaminophen concentrations were higher; therefore, pharmacokinetic alterations were more easily discerned, in Sprague-Dawley than in Wistar rats. It is concluded that the Sprague-Dawley strain is a more suitable model for the study of pharmacokinetic alterations induced by spinal cord injury.

Casimiroa edulis seed extracts show anticonvulsive properties in rats.

A single dose of 5, 10 and 100 mg/kg of Casimiroa edulis aqueous extract (AQ); 10, 100 and 1000 mg/kg of C. edulis ethanolic extract (E-OH); in addition, 10, 30 and 12 mg/kg of propyleneglycol (Pg), phenytoin (Phen) and phenobarbital (Phb) was orally given to adult male Wistar rat groups. Thereafter, all groups were assayed for protection against maximal electroshock (MES) and pentylenetetrazole (METsc) seizure inducing tests at hourly intervals throughout 8 h. For MES, a maximal protection of 70% at the 2nd and 4th h with 10 mg/kg AQ and 100 mg/kg E-OH doses, occurred. That of Phen, Phb and Pg was 80, 90 and 10% at the 8th, 6th and 2nd h, respectively. The averaged values of the MES unprotected rats under 10 and 100 mg/kg of AQ and E-OH extracts, showed that a shortened reflex duration as well as a delayed latency and uprising times occurred. On the other hand, just an enlarged latency and no protection against METsc device in AQ and EOH was observed. Phen and Phb maximal protection was 80 and 100% at the 4th and 6th hour against METsc. Thus, AQ is tenfold more potent anticonvulsive extract than E-OH against MES.

Anticonvulsant activity of Casimiroa edulis in comparison to phenytoin and phenobarbital.

An aqueous extract of Casimiroa edulis leaves was tested in adult male Wistar rats for anticonvulsant activity utilizing two models of experimental epilepsy: maximal electroshock seizure (MES) and subcutaneously injected metrazole (METsc). Single dose of 100 mg/kg C. edulis vacuum dried aqueous extracts (VDA) orally administered to experimental animals elicited 50% and 70% abolition of MES and METsc-induced seizures, respectively. Two firmly established antiepileptic drugs in human therapy, phenytoin (PHT) and phenobarbital (PB), abolished 90% of MES-induced seizures, whereas an 80% and 100% absence of clonic seizures was attained in METsc test, correspondingly. The seizure abolition observed in C. edulis VDA treated rats was comparable with the anticonvulsive pattern exhibited by PHT and PB. These results suggest that potencially antiepileptic compounds are present in C. edulis extracts that deserve the study of their identity and mechanism of action.

In vitro inhibition of microbial methane production by 9,10-anthraquinone.

Monensin, 2,2-dichloroacetamide, and 9,10-anthraquinone were incubated for 24 h in ruminal fluid and buffer with 100:0, 50:50, and 10:90 forage-concentrate diets. Monensin (.5 ppm of the fluid) increased (P < .05) the molar proportion of propionate in the 50 and 100% forage diets but not in the high concentrate diet. At the same level of addition, 2,2-dichloroacetamide increased (P < .05) the molar proportion of propionate only in the 50:50 forage-concentrate diet. Relative to control cultures, monensin and 2,2-dichloroacetamide numerically decreased methane production in the 10 and 100% forage diets and decreased (P < .05) methane in the 50% forage diet. Hydrogen production was unaffected by treatment. Lack of an effect on fermentation end products in the high concentrate diet was probably a result of the low dose levels. In general, increasing levels of 9,10-anthraquinone (.5, 1.0, and 5.0 ppm) reduced total VFA concentration and the molar proportion of acetate, and increased propionate, butyrate and valerate. Increasing levels of 9,10-anthraquinone caused linear and quadratic decreases (P < .05) in methane production, and increases (P < .05) in hydrogen. There were no consistent effects on ammonia concentration in culture fluid from any of the compounds. In continuous culture of a 10:90 forage-concentrate diet, addition of 9,10-anthraquinone (10 ppm of the fluid/12 h) caused changes similar to those observed in batch culture with the exception of a decreased (P < .05) molar percentage of propionate, which may have been due to the high dose. The data are interpreted to indicate that 9,10-anthraquinone has the ability to alter in vitro microbial fermentation.

[Diverticulum of the right ventricle with biventricular myocardiopathy]. / Divertículo de ventrículo derecho con miocardiopatía biventricular.

We report a 18-days-old newborn boy with right ventricular diverticulum associated with biventricular cardiomyopathy, diagnosed by two-dimensional and Doppler echocardiography and angiography. Heart transplant was carried out at the age of four months, dying the next day. The histologic study showed endocardial fibroelastosis.

[Assessment with the Epworth scale of daytime somnolence in patients with suspected obstructive apnea syndrome during sleep. Differences between patients and their partners]. / Valoración mediante escala de Epworth de la somnolencia diurna en pacientes con sospecha de síndrome de apneas obstructivas durante el sueño. Diferencias entre los pacientes y sus parejas.

UNLABELLED: Daytime sleepiness is an important symptom in obstructive sleep apnea syndrome. The Epworth sleepiness scale gives a subjective estimate of the level of sleepiness by asking the patient to estimate the probability of falling asleep during each of eight activities of daily living. OBJECTIVE: We aimed to see whether patients suspected of sleep apnea and their partners or other living companions assessed daytime sleepiness differently. MATERIAL AND METHOD: One hundred fifty-nine consecutive patients referred for suspicion of sleep respiratory disorder were studied. Patients and their partners assessed sleepiness separately using the Epworth scale. RESULTS: One hundred forty subjects were men and 19 were women. The mean global Epworth score provided by the patients was significantly lower than that of their companions (10 +/- 0.37 versus 11 +/- 0.42; p < 0.001). However, the two were closely correlated (rho = 0.79). CONCLUSION: Our results indicate that living companions' subjective Epworth scale assessment of sleepiness is greater than is that of patients themselves.

[Assessment of excessive day-time sleepiness in professional drivers with suspected obstructive sleep apnea syndrome]. / Evaluación de la somnolencia diurna excesiva en conductores profesionales con sospecha de síndrome de apnea obstructiva durante el sueño.

Excessive daytime sleepiness is a common symptom of obstructive sleep apnea syndrome (OSAS) and can be a cause of traffic accidents, creating a problem of particular importance for professional drivers given the associated death, disability and professional repercussions. We assessed whether the Epworth sleepiness scale (ESS), which is a subjective measure of daytime sleepiness, correlates well with multiple sleep latency (MSL) testing, which gives an objective measure of daytime sleepiness. We also compared each method with the results of polysomnography (apnea-hypopnea index, arousal index and minimum oxygen saturation). We studied 55 professional drivers suspected of OSAS. All answered the ESS questionnaire and underwent polysomnographic and MSL testing. We found a significant, though not relevant, correlation between the degree of excessive daytime sleepiness estimated by the ESS and by MSL testing (r = -0.41; p = 0.002). A significant, though weak, correlation was found between the ESS score and the arousal index (r = 0.26; p < 0.05). Our results do not clarify which method is best for measuring excessive daytime sleepiness in professional drivers suspected of OSAS.

[Analysis of the nutritional state of school children in different districts of the province of Granada (Spain)]. / Análisis del estado nutricional en escolares; estudio por áreas geográficas de la provincia de Granada (España).

BACKGROUND: In Spain the prevalence of obesity shows a north-south distribution. In the province of Granada its distribution is unknown. OBJECTIVES: (1) To study the prevalence of overweight and obesity in a sample population of school children and adolescents from different districts in the province of Granada. (2) To verify whether there are significant differences, depending on the district where the students reside. (3) To find a possible correlation between the nutritional state of the students and that of their parents. METHODS: The population sample was composed of 977 school children and adolescents from 9 to 17 years of age, attending 13 public elementary schools and high schools in the city and province of Granada (Spain). In this analytical and multicentric study, the nutritional state of the subjects was evaluated by means of anthropometric measurements. Furthermore, data were collected by means of questionnaire to discover whether the respondents had a family history of overweight or obesity. RESULTS: We found a high prevalence of overweight and obesity among the studied population. In girls, the greater prevalence of both overweight and obesity ranged from 12 to 14 years of age. In boys, there was an increase in the prevalence of overweight at twelve years of age. Regarding obesity, their rates were significantly lower than those described among girls. There were statistically significant differences for weight (F = 4,154; p = 0,003) but not for height (F = 1,928; p =0,105). But for the variable BMI was statistically significant difference (F = 5.037; P < 0.001) between the studied geographical areas. The results showed that the nutritional state of students with a family history of obesity was significantly worse (p < 0.01). DISCUSSION: A high prevalence of obesity was found in the sample, especially among the girls. There exists a geographical distribution pattern, possibly derived from the socioeconomic characteristics of each area in the province. The existence of a family history of obesity is an important factor that can determine whether the child will also become obese in the future.

[Analysis of the nutritional state and body composition of school children in Granada (Spain)]. / Análisis del estado nutricional y composición corporal de una población de escolares de Granada.

The objective of this study was to first determine the nutritional state of a sample population of school children, and then analyze the distribution pattern of their subcutaneous fat layer. The sample was composed of 977 school children from the city and province of Granada (Spain). All of the children (524 girls and 452 boys) were 9-17 years of age. To study their nutritional state and the distribution of the subcutaneous fat layer, they were given a complete anthropometric evaluation, which included measuring their weight, height, body mass index, skin folds, and body perimeters. The results obtained showed a 23.01% prevalence of overweight in the female subjects and 20.81% in the male subjects. Furthermore, the female subjects had an obesity prevalence of 12.70% in comparison to the male subjects, whose obesity prevalence was 4.98%. The distribution pattern of subcutaneous fat was found to be mainly located in the central part of body. The high percentage of overweight and obesity along with the development of a central fat distribution pattern (neck, chest, and abdomen) in these school children is clear evidence of potential cardiovascular risk.