[Assessment of changes in body composition in critically ill patients]. / Valoración en la variación de la composición corporal del enfermo crítico.

Critically ill patients are especially prone to malnutrition because their hypermetabolic state produces an increase in nutritional requirements that often are not covered with the formulae supplied. Evaluation of the body composition (BC) makes it possible to quantify the main structural components of the body: muscle, bone and fat. An anthropometry study was made for the assessment of these elements to obtain information on the protein-calorie nutritional status of critically ill patients. We have aimed to describe the variations in the BC of the critical ill patient during the first seven days after ICU admission. The observational study included 50 critically ill patients, of whom 78% were male and 22% women with a mean age of 56 years. Height, weight, body mass index (BMI), bone diameters, muscle perimeters and skinfolds of patients were recorded. The body composition (BC) calculations were performed using the Faulkner, Rocha, Wurch and Matiegka formulae. We obtained the baseline energy expenditure of each patient with the Harris-Benedict formula. After analyzing the data, a decrease was found in the percentage of muscle mass (mean+/-SD: 3+/-0.76), an increase in the percentage of body fat (2+/-0.76) and an increase in BMI at the expense of an augment of weight. We have concluded that during the first week of ICU admission patients lose critical muscle mass and have an increase in fat mass. Awareness of these changes in the BC of patients may be useful to determine the appropriate nutrition for critically ill patients.

[Localization of sentinel node in squamous cell carcinoma of the penis. Initial experience]. / Localización del ganglio centinela en el carcinoma escamoso de pene. Experiencia inicial.

OBJECTIVE: To assess the validity of radioguided sentinel node biopsy in squamous cell penile carcinoma. MATERIAL AND METHODS: Fifteen patients were studied. The first 5 patients were included in a group for validation of the technique, in which a standard inguinal lymphadenectomy was performed after the procedures described below. The remaining 10 patients were included in the technique application group. The day before surgery, lymphoscintigraphy was performed on all patients. During the operation, radioguided biopsy to locate the sentinel node was done. Methylene blue dye was injected shortly before surgery in 10 patients. All patients were followed for an average of 32 months. RESULTS: In the validation group, lymphoscintigraphy revealed inguinal drainage in 5/5 patients. Unilateral metastases were detected in 3/5 patients. No metastatic nodes were detected among the nodes removed during inguinal lymphadenectomy. In the application group, lymphoscintigraphy showed inguinal drainage in 9/10 patients. Nineteen nodes were removed, none of which showed tumour involvement. During the follow-up period, no disease progression or recurrence were observed in either patient group. CONCLUSIONS: Radioguided localization and biopsy of the sentinel nodes can avoid unnecessary lymphadenectomies in patients with squamous cell penile carcinoma and high or intermediate risk of lymph node involvement. This technique shows high reliability and negative predictive value in penile carcinoma.

Sperm origin impact on early human embryo kinetics / El origen del gameto paterno influye en la cinética embrionaria temprana

Introduction: Time-lapse imaging in embryology is a recent and developing technology, which not only allows constant embryo monitoring but is also a promising non-invasive tool for embryo selection, as it permits the annotation of the embryo's kinetics throughout early development. Several external factors together with patient characteristics are reported as affecting embryo kinetics. Controversy still exists regarding whether sperm origin affects the timing of the embryo's developmental events evaluated by time-lapse monitoring. The aim of this study is to examine the effect of sperm origin on embryonic kinetics in IVF cycles. Material and methods: A retrospective analysis of 161 IVF cycles between 2014 and 2020 were included. The morphokinetic parameters of 220 embryos obtained from couples with severe male factor infertility who underwent testicular sperm extraction (TESE), and 613 embryos from couples with fresh ejaculated spermatozoa were evaluated. Results: Statistically significant morphokinetic differences were observed between embryos from the TESE group compared to the normozoospermic embryos. In fact, 7 kinetic variables were eventually found to be relevant (p<.05). Conclusions: This study showed that embryos derived from testicular-retrieved spermatozoa presented delayed cell divisions, compared to ejaculated spermatozoa embryos.(AU)

Introducción: La tecnología time-lapse en embriología es una metodología de aplicación reciente en los laboratorios de fecundación in vitro (FIV), que además de la monitorización continua de los embriones, permite realizar anotaciones sobre la morfología y la cinética del desarrollo embrionario que pueden emplearse en la selección de embriones. Se ha descrito que la cinética de los embriones en cultivo varía en función de múltiples factores, como la estimulación ovárica, los medios de cultivo empleados, las condiciones de cultivo, etc. Se desconoce cuál es el efecto paterno en la cinética embrionaria y si este efecto depende del origen de los espermatozoides. El objetivo de este estudio es evaluar el efecto del origen de los espermatozoides sobre la cinética embrionaria en los ciclos FIV. Material y métodos: Para ello, se analizaron retrospectivamente 161 ciclos de FIV entre los años 2014 y 2020. Se incluyeron 220 embriones de parejas con infertilidad por factor masculino severo que se sometieron a una biopsia para la recuperación de esperma testicular (TESE) y 613 embriones derivados del eyaculado fresco de varones normozoospérmicos. Resultados: Se observaron diferencias estadísticamente significativas entre los embriones que se originaron en el grupo TESE, en comparación con los normozoospérmicos. De hecho, se encontraron siete variables cinéticas relevantes (p<0,05). Conclusiones: Este estudio muestra que los embriones derivados de espermatozoides recuperados por biopsia testicular presentan un patrón de división tardío, en comparación con los embriones provenientes de espermatozoides del eyaculado.(AU)

Antitumor properties of podophyllotoxin and related compounds.

The lignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, lignans, and especially cyclolignans, have been the objective of numerous studies focused to prepare better and safer anticancer drugs. The mechanism by which podophyllotoxin blocks cell division is related to its inhibition of microtubule assembly in the mitotic apparatus. However, etoposide and teniposide were shown not to be inhibitors of microtubule assembly which suggested that their antitumor properties were due to another mechanism of action, via their interaction with DNA and inhibition of DNA topoisomerase II. Other podophyllotoxin derivatives has also been reported which retained or even improved the cytotoxic activity, but these were weak inhibitors of topoisomerase II in vitro; the data revealed that such analogs exhibit a different, as yet unknown, mechanism of action. The main deficiency of these compounds is their cytotoxicity for normal cells and hence side effects derived from their lack of selectivity against tumoral cells. In this regard it is necessary to investigate and prepare new more potent and less toxic analogs, that is, with better therapeutic indices. It is well accepted from structure-activity studies in this field that the trans-lactones are more potent as antineoplastics than the cis-lactones. Not only the configuration of the D ring is an important factor for high cytotoxic activity, but also a quasi-axial arrangement of the E ring is necessary. On this basis, studies on lignans have been addressed to modify the lactone moiety and prepare analogs with heteroatoms at different positions of the cyclolignan skeleton. Our group has been working during the last few years on chemical transformations of podophyllotoxin and analogs and we have prepared a large number of cyclolignan derivatives some of which display potent antiviral, immunosuppressive and cytotoxic activities. We have reported several new cytotoxic agents with nitrogen atoms at C-7 or C-9 or at both C-7 and C-9: imine derivatives, oxime derivatives, pyrazoline-, pyrazo- and isoxazoline-fused cyclolignans. At present, we are preparing mainly new compounds by modifications of the A and E cyclolignan-rings. They are being tested on cultures of different tumoral cell lines (P-388 murine leukemia, A-549 human lung carcinoma, HT-29 human colon carcinoma and MEL-28 human melanoma) and some of them have shown an interesting and selective cytotoxicity.

Rapid suppression of drive for a parasitic B chromosome.

The persistence of parasitic B chromosomes in natural populations depends on both B ability to drive and host response to counteracting it. In the grasshopper Eyprepocnemis plorans, the B24 chromosome is the most widespread B chromosome variant in the Torrox area (Málaga, Spain). Its evolutionary success, replacing its ancestral neutralized B variant, B2, was based on meiotic drive in females, as we showed in a sample caught in 1992. In females collected six years later, mean B24 transmission ratio (k(B)) was 0.523, implying a very rapid decrease from the 0.696 observed in 1992. This shows that B24 neutralization is running very fast and suggests that it might most likely be based on a single gene of major effect.

Immunosuppressive cyclolignans.

The immunosuppressive activity of several lactonic, nonlactonic, and heterocycle-fused cyclolignans has been demonstrated for the first time by use of a T-cell-mediated immune response. Of the compounds tested, 4'-demethyldeoxypodophyllotoxin (8), beta-apopicropodophyllin (6), and the isoxazoline-fused cyclolignan 15 are the most potent with respect to their suppression of activated splenocytes.

New selective cytotoxic diterpenylquinones and diterpenylhydroquinones.

A new series of diterpenylquinone/hydroquinones has been prepared by Diels-Alder cycloaddition between three labdanic diterpenoids (myrceocommunic acid, methyl myrceocommunate, and myrceocommunyl acetate) and p-benzoquinone or 1,4-naphthoquinone. Influences of the quinone/hydroquinone fragment and other structural features, such as the different functionalities in the terpenic core, are considered in relation to the cytotoxicity toward neoplastic cells and the selectivity of these diterpenylnaphthoquinones/hydroquinones and anthraquinones. Several compounds showed IC50 values under the micromolar level, and four of these derivatives were evaluated at the NCI screening panel. The results showed an important selectivity toward renal cancer lines, identifying these compounds as a very promising group of antineoplastics.

Host recombination is dependent on the degree of parasitism.

Parasites and hosts are involved in a continuous coevolutionary process leading to genetic changes in both counterparts. To understand this process, it is necessary to track host responses, one of which could be an increase in sex and recombination, such as is proposed by the Red Queen hypothesis. In this theoretical framework, the inducible recombination hypothesis states that B-chromosomes (genome parasites that prosper in natural populations of many living beings) elicit an increase in host chiasma frequency that is favoured by natural selection because it increases the proportion of recombinant progeny, some of which could be resistant to both B-chromosome effects and B-accumulation in the germline. We have found a clear parallelism between host recombination and the evolutionary status of the B-chromosome polymorphism, which provides explicit evidence for inducible recombination and strong support for the Red Queen hypothesis.

Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives.

Several podophyllotoxin derivatives modified in the A, B, C, D and E rings were prepared from podophyllotoxin and methyl isoxazopodophyllic acid and evaluated for their cytotoxicity on several neoplastic cell lines. Chemical transformations performed on these compounds have yielded derivatives more potent and more selective that the parent compound. Most of the compounds maintained their cytotoxicity at the microM level. Distribution, biosynthesis, production, biotechnology, applications and synthesis have also been reviewed.

Inhibition of human sPLA2 and 5-lipoxygenase activities by two neo-clerodane diterpenoids.

The inhibitory effect of two neo-clerodane diterpenoids, E-isolinaridial (EI) and its methylketone derivative (EIM), isolated from Linaria saxatilis var. glutinosa, on PLA2 and other enzyme activities involved in the inflammatory process was studied. Both compounds inhibited human synovial sPLA2 in a concentration-dependent manner with IC50 values of 0.20 and 0.49 microM, respectively, similar to scalaradial. Besides, these compounds decreased the cell-free 5-lipoxygenase activity and A23187-induced neutrophil LTB4 biosynthesis. Another function of human neutrophils, such as receptor-mediated degranulation, was also significantly reduced. In contrast, none of the compounds affected superoxide generation in leukocytes, or cyclooxygenase-1, cyclooxygenase-2 and inducible nitric oxide synthase activities in cell-free assays.

Free to complexed PSA ratio in differentiating benign prostate hyperplasia from prostate cancer.

BACKGROUND: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.

Synthesis and antineoplastic activity of cyclolignan aldehydes.

Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a selective antitumour agent against the HT-29 colon carcinoma, have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained their cytotoxicity at, or under, the microM level.

Structure- and species-dependent insecticidal effects of neo-clerodane diterpenes.

Several natural neo-clerodane diterpenoids isolated from Linaria saxatilis and some semisynthetic derivatives were tested against several insect species with different feeding adaptations. The antifeedant tests showed that the oliphagous Leptinotarsa decemlineata was the most sensitive insect, followed by the aphid Myzus persicae. The polyphagous Spodoptera littoralis was not deterred by these diterpenoids; however, following oral administration, some of these compounds did have postingestive antifeedant effects on this insect. In general terms, the antifeedant effects of these compounds were species-dependent and more selective than their toxic/postingestive effects. The study of their structure-activity relationships showed that both the decalin moiety and the chain at C-9 determined their bioactivity. Furthermore, the presence of a 4,18-epoxy/diol moiety was an important feature for both the antifeedant and the toxic/postingestive effects.

Cytotoxic cyclolignans related to podophyllotoxin.

The cyclolignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, cyclolignans have been the objective of numerous studies focused to prepare better and safer anticancer drugs. Several cyclolignans related to podophyllotoxin have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28); some of them have antiviral and immunosuppressive activities.

[Liver dysfunction associated with total parenteral nutrition]. / Disfunción hepática asociada a nutrición parenteral total.

An evaluation is made of liver malfunctions in patients receiving TPN over a period of > or = 15 days between 1989 and 1991. Use was made of the monitoring records on patients undergoing TPN and, subsequently, of clinical records, with analysis of diagnoses and type of intervention, the biochemical parameters (SGOT, SGPT, GGT, FA, LDH, and total and direct bilirubin), and the type and degree of malnutrition, nutritional backup, associated medication, etc. A group of patients was excluded from the study on the basis of the following criteria: liver-biliary disease, cardiac insufficiency, liver metastasis, sepsis, kidney insufficiency and hepatotoxic drugs. Of 237 patients, 75 (31.64%) had liver alterations: following application of the exclusion criteria, 24 patients (10.12%) were taken with liver alterations attributable to the TPN. Macro- and micronutrients were included in the TPN. We found no relation between the kcal/kg of weight, nor with the quantity of glucose and fats nor of nitrogen, calculated according to individual requirements: they remained within the limits established. No serious case of cholestatic jaundice was encountered. Moderate to severe malnutrition was found in 50% of patients, so that this must be treated as a risk factor. GGT is the first enzyme to alter; this occurred in the largest proportion of patients (91.66%), followed by SGPT. FA and GOT are altered in the same percentage of patients. Biochemical parameter monitoring is essential in patients undergoing TPN, not only for appraisal of the nutritional state but also to prevent or correct potential serious metabolic complications.

[The protocolization and follow-up of enteral nutrition. 2 years of experience]. / Protocolización y seguimiento de la nutrición enteral. Dos años de experiencia.

The Artificial Nutrition Unit was set up in 1980 in the Pharmacy Service, with the objective of preparing parenteral nutritional units. Different protocols were prepared, approved by the Commission of Pharmacy and Therapeutics. From 1986 onwards, follow-up was commenced and since March 1988, nutritional evaluation of the patients on enteral nutrition has been performed. Encouraged by the results obtained, a proposal for protocolizing enteral nutrition was put to the Commission of Pharmacy and Therapeutics, which was approved in December 1988. The main objective was to select the enteral diets which would be used as a formula for existing hospital diets and, after establishing this formula, protocolize the indications that would assists in selecting from among the diets available, the ones that would best adapt to the individual needs of each patient. As a secondary objective, the Artificial Nutrition Unit took on the responsibility of processing the medical instructions and dispensing enteral diets using the dosage/patient/day distribution system. It also provides information to medical and nursing staff on existing diets, as well as on rules for administration and storage in nursing units, providing when necessary the most suitable containers, equipment and pumps for administering the diets. It also carries out a nutritional evaluation of patients exclusively on enteral nutrition, as well as follow-up of these. Finally, it prepares the monthly actual cost figures generated by each nursing unit, since diets not administered after twenty-four hours are returned to the Nutrition Unit. One problem existing is the non-administration of products or patients who refuse to take their diets.(ABSTRACT TRUNCATED AT 250 WORDS)

[A multivariate analysis approach to antineoplastic and antiviral structure-activity relationships to a series of podophyllotoxins]. / Approche par analyse multivariée des relations structure-activités antitumorale et antivirale dans la série de la podophyllotoxine.

In this work, the authors have used technics of multivariate analysis to determine the structure-activity relationships of 46 podophyllotoxin derivatives and analogs studied for their antineoplastic and antiviral activities. The obtained results allow to envisage the possible synthesis of more specific molecules by making modifications in the structure of the model molecular archetype.

Expression of anatomical leaf traits in homoploid hybrids between deciduous and evergreen species of Vaccinium.

We investigated the anatomical expression of leaf traits in hybrids between evergreen Vaccinium vitis-idaea and deciduous V. myrtillus. We compared parents from four populations with their respective F1 hybrids and tested whether (i) transgression can be the source of novel anatomical traits in hybrids; (ii) expression of transgressive traits is more probable for traits with similar values in parents and intermediate for more distinct values, as predicted by theory; and (iii) independent origin of hybrids leads to identical trait expression profiles among populations. We found that anatomical leaf traits can be divided into four categories based on their similarity to parents: intermediate, parental-like, transgressive and non-significant. Contrary to the common view, parental-like trait values were equally important in shaping the hybrid profile, as were intermediate traits. Transgression was revealed in 17/144 cases and concerned mainly cell and tissue sizes. As predicted by theory, we observed transgressive segregation more often when there was little phenotypic divergence, but intermediate values when parental traits were differentiated. It is likely that cell and tissue sizes are phylogenetically more conserved due to stabilising selection, whereas traits such as leaf thickness and volume fraction of the intercellular spaces, showing a consistent intermediate pattern across populations, are more susceptible to directional selection. Hybrid populations showed little similarity in expression profile, with only three traits identically expressed across all populations. Thus local adaptation of parental species and specific genetic background may be of importance.

Prediction of carcass composition, ham and foreleg weights, and lean meat yields of Iberian pigs using ultrasound measurements in live animals.

The most valuable lean cuts from Iberian pigs are the hams, forelegs, and loins, which yield high quality cured meat products. This study aimed to assess the correlation between body composition measurements taken in vivo by ultrasonography in Iberian pigs and those taken on the carcass, which were then used to develop predictive models to estimate the weight and yield of these cuts. Before slaughter, 241 Iberian pigs were weighed (slaughter BW) and ultrasonically scanned. Ultrasound images were collected at 3 locations: the 10th intercostal space, caudal to the last rib to image the loin muscle, and the rear gluteal region [ultrasound gluteal backfat (u-GBF)]. After slaughter, the weight of the carcass (CW), ham (HW), foreleg (FW), and loin (LW) were determined, and the sum of these lean cuts weights (CLPW) and the corresponding yields were calculated. A portion of loin with the associated bones, backfat, and skin was obtained by cutting the carcass between the 10th and last ribs and was used to measure, at the 10th (10) and last (14) rib locations, the total backfat thickness, the area of the loin muscle (c-LA), and the thickness of the 4 backfat (BF) layers, namely, the outer (c-OBF), middle (c-MBF), outer plus middle (c-OMBF), and the inner (c-IBF). Finally, intramuscular fat percentages (IMF) were obtained from the meat samples. Corresponding measurements from the ultrasound (u) images were similarly taken at the same 2 ribs (u-BF, u-LA, u-OBF, u-MBF, u-OMBF, and u-IBF). The correlation was greatest between u-MBF10 and c-MBF10 (0.84). Most correlations between ultrasound and carcass measurements were lower at the last rib than at 10th rib. The greatest correlation of IMF10 occurred with u-IBF10 (0.40). Ham weight and HL were more correlated with u-BF10 than with u-BF14 whereas FW was more correlated with u-BF14. The u-LA was more correlated with HW, FW, and LW at the last rib than at the 10th rib. Slaughter live weight accounted for 0.84, 0.42, 0.36, and 0.54% of the variation for the prediction of CW, HW, FW, and CLPW, respectively. The u-LA10 and u-LA14 increased the variation explained by the model up to 0.89, 0.48, 0.39, and 0.62% for CW, HW, FW, and CLPW, respectively. Including u-GBF in the models also increased the R(2) values for predicting HW, LW, HY (ham yield), and LY (loin yield). In conclusion, u-LA10, u-LA14, and u-GBF may improve weight of commercial cuts and yield prediction in live Iberian pigs.

Applicability of 2-DE to assess differences in the protein profile between cold storage and not cold storage in nectarine fruits.

Cold storage is being used to increase nectarine fruits' postharvest life. However, low temperatures lead to chilling injury and limit their commercial quality and value. In this study a proteomic approach was used to compare the protein profile between control and cold storage nectarine fruits. Protein extracted from tissue was resolved by two-dimensional gel electrophoresis (2-DE) in the 4-7 pH and 10-200 kDa Mr range. Around 350 spots were well determined, and 11 from 17 spots that showed significant differences were identified by peptide mass fingerprinting (PMF) using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS). Four differentially expressed proteins were characterized as allergens and were further assessed at the transcription level using quantitative real time-RT-PCR (qRT-PCR).