Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.

Dysregulated cathepsin activity is linked to various human diseases including metabolic disorders, autoimmune conditions, and cancer. Given the overexpression of cathepsin in the tumor microenvironment, cathepsin inhibitors are promising pharmacological agents and drug delivery vehicles for cancer treatment. In this study, we describe the synthesis and photochemical and biological assessment of a dual-action agent based on ruthenium that is conjugated with a cathepsin inhibitor, designed for both photodynamic therapy (PDT) and photochemotherapy (PCT). The ruthenium-cathepsin inhibitor conjugate was synthesized through an oxime click reaction, combining a pan-cathepsin inhibitor based on E64d with the Ru(II) PCT/PDT fragment [Ru(dqpy)(dppn)], where dqpy = 2,6-di(quinoline-2-yl)pyridine and dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine. Photochemical investigations validated the conjugate's ability to release a triazole-containing cathepsin inhibitor for PCT and to generate singlet oxygen for PDT upon exposure to green light. Inhibition studies demonstrated the conjugate's potent and irreversible inactivation of purified and intracellular cysteine cathepsins. Two Ru(II) PCT/PDT agents based on the [Ru(dqpy)(dppn)] moiety were evaluated for photoinduced cytotoxicity in 4T1 murine triple-negative breast cancer cells, L929 fibroblasts, and M0, M1, and M2 macrophages. The cathepsin inhibitor conjugate displayed notable selectivity for inducing cell death under irradiation compared to dark conditions, mitigating toxicity in the dark observed with the triazole control complex [Ru(dqpy)(dppn)(MeTz)]2+ (MeTz = 1-methyl-1H-1,2,4-triazole). Notably, our lead complex is among a limited number of dual PCT/PDT agents activated with green light.

Predictive factors of destination at discharge after spinal cord injury.

INTRODUCTION: One of the main goals of the rehabilitation of patients with spinal cord injury (SCI) is the reintegration of the individual to their family, social, and work setting. The objective of this study was to identify the factors that determine the discharge destination after a traumatic spinal cord injury. MATERIAL AND METHODS: We conducted a retrospective descriptive study of 305 patients with SCI who completed the rehabilitation treatment at the spinal injury unit of Hospital Insular de Gran Canaria between 2001 and 2018. RESULTS: During the study period, we observed an increase in the number of patients referred to long-term care centres, from 9.14% between 2001 and 2010 to 18.4% between 2011 and 2018 (P < .01). Of 20 variables that presented a significant association with destination at discharge in the univariate study, 7 presented a significant association in the multivariate study: age (OR: 1.05; 95% CI, 1.02-1.08), living with a partner (OR: 0.26; 95% CI, 0.09-0.76), residing on another island (OR: 3.57; 95% CI, 1.32-9.63), smoking (OR: 3.44; 95% CI, 1.26-9.44), diabetes (OR: 6.51; 95% CI, 1.46-29.02), history of psychiatric disorders (OR: 3.79; 95% CI, 1.31-10.93), and scores on the Spinal Cord Independence Measure-III (SCIM-III) (OR: 0.48; 95% CI, 0.33-0.69). CONCLUSIONS: Our findings identified advanced age, living on the island of Tenerife, not being married, smoking, type 2 diabetes mellitus, history of psychiatric disorders, and low SCIM-III scores as predictive factors of referral to a long-term care centre in patients with traumatic SCI in the Canary Islands.

Calcium homeostasis behavior and cardiac function on left ventricular remodeling by pressure overload

Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and sarcolemmal Na+/Ca2+ exchanger (NCX1) structures are involved in heart cell Ca2+ homeostasis. Previous studies have shown discrepancies in their function and expression in heart failure. The goal of this study was to evaluate heart function and hypertrophied muscle Ca2+-handling protein behavior under pressure overload. Twenty male Wistar rats were divided into two groups: Aortic stenosis (AoS), induced by a clip placed at the beginning of the aorta, and Control (Sham). After 18 weeks, heart function and structure were evaluated by echocardiogram. Myocardial function was analyzed by isolated papillary muscle (IPM) at basal condition and Ca2+ protein functions were evaluated after post-pause contraction and blockage with cyclopiazonic acid in IPM. Ca2+-handling protein expression was studied by western blot (WB). Echocardiogram showed that AoS caused concentric hypertrophy with enhanced ejection fraction and diastolic dysfunction inferred by dilated left atrium and increased relative wall thickness. IPM study showed developed tension was the same in both groups. AoS showed increased stiffness revealed by enhanced resting tension, and changes in Ca2+ homeostasis shown by calcium elevation and SERCA2a blockage maneuvers. WB revealed decreased NCX1, SERCA2a, and phosphorylated phospholambam (PLB) on serine-16 in AoS. AoS had left ventricular hypertrophy and diastolic dysfunction compared to Sham; this could be related to our findings regarding calcium homeostasis behavior: deficit in NCX1, SERCA2a, and phosphorylated PLB on serine-16.

Nutritional, behavioral and performance parameters of F1 Holstein x Zebu cows at different lactation stages / [Parâmetros nutricionais, comportamento ingestivo e desempenho de vacas F1 Holandês x Zebu em diferentes estádios da lactação]

The objective of this study was to evaluate the different lactation stages of F1 Holstein x Zebu cows on intake and digestibility of nutrients, nitrogen use efficiency, feeding behavior and performance. Thirty-six F1 Holstein × Zebu cows with initial body weight (BW) of 482±43kg were used. The early, mid and late lactation stages were characterized after 50±13, 111.5±11.75 and 183.0±17.5 days in milk, respectively. A completely randomized design with three lactation stages and 12 cows in each treatment group was used. Dry matter intake (P=0.01) was higher in late lactation. Milk yield (P<0.01) was 24.17% higher in early lactation than in other stages. Body weight was lowest in mid-lactation cows (465.63kg; P<0.01). The feed efficiency was 23.36% higher in early lactation than in other stages (0.82kg of milk/kg of DM). F1 Holstein x Zebu cows have increased dry matter intake in late lactation. Milk yield and feed efficiency in early lactation were benefited by changes in feeding behavior, such as increased rumination time.(AU)

O objetivo deste estudo foi avaliar os diferentes estágios de lactação de vacas F1 Holandês x Zebu quanto ao consumo e à digestibilidade de nutrientes, à eficiência no uso de nitrogênio, ao comportamento ingestivo e ao desempenho. Trinta e seis vacas F1 Holandês × Zebu, com peso corporal inicial (PC) de 482±43kg, foram utilizadas. Os estágios inicial, médio e final da lactação foram caracterizados após 50±13, 111,5±11,75 e 183,0±17,5 dias de lactação, respectivamente. O arranjo experimental adotado foi o delineamento inteiramente ao acaso, com três fases de lactação e 12 vacas em cada grupo de tratamento. O consumo de matéria seca (P=0,01) foi maior no período final da lactação. Na fase inicial da lactação, a produção de leite (P<0,01) foi maior em 24,17% em comparação às demais fases. Na fase intermediária da lactação, as vacas apresentaram menor peso corporal (465,63kg; P<0,01) em relação às demais fases. A eficiência alimentar foi maior em 23,36% na fase inicial da lactação (0,82kg de leite/kg de MS). Vacas F1 Holandês x Zebu aumentam o consumo de matéria seca no período final da lactação. A produção de leite e a eficiência alimentar no início da lactação foram favorecidas por mudanças no comportamento ingestivo, como o aumento do tempo de ruminação.(AU)

Seminoma in an adult striped dolphin Stenella coeruleoalba: tomographic, macroscopical, histological and immunohistochemical study.

Testicular neoplasms have been extensively described and characterized in domestic animals, but reports in wildlife species, including marine mammals, are scarce. This case report describes a testicular seminoma in an adult striped dolphin Stenella coeruleoalba stranded along the coasts of the Canary Islands. Post-mortem computerized tomography (CT) showed a prominent enlargement of the cranial pole of the right testicle, displacing the intestinal loops. Necropsy gross findings confirmed the presence of a testicular mass, bulging at the cut surface, with multiple well-delimitated whitish nodular lesions. Histologically, intratubular and diffuse neoplastic germinative cell proliferation was described. Complementary immunohistochemical assessments for vimentin and CD117 antibodies were negative. To the authors' knowledge, this is the first seminoma described in a S. coeruleoalba. We suggest that post-mortem (PM) pre-necropsy CT in dolphins is a useful tool for anatomic-guided pathology in such cases.

Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain.

This study evaluated the effects of rosuvastatin in vivo on toxoplasmosis chronic infection. Thirty-five Swiss mice were orally infected (ME-49 strain). After 50 days, the mice were separated into five groups: GI - non-infected, GII - infected, GIII - infected and treated with pyrimethamine and sulfadiazine (12.5 + 50 mg kg-1 body weight day-1), GIV and GV - infected and treated with rosuvastatin 10 and 40 mg kg-1 body weight day-1, respectively. After 21 days, we collected blood, liver, lungs, femoral biceps and brain were removed for Toxoplasma gondii DNA quantification by qPCR and histopathological analysis. GIV and GV did not present premature death or clinical changes, and the hepatic enzyme levels were lower compared to GI. Toxoplasma gondii DNA was detected mainly in brain and muscle, but the parasite load was significantly lower in GV compared to GII brains (P < 0.05). Histopathological changes were observed in brains, with T. gondii cysts as well as an inflammatory condition, including necrosis areas in GII and GIII. These data confirm active infection with tissue injury. This inflammatory condition was attenuated in the groups treated with rosuvastatin, especially R40 (GV). Our findings demonstrated the in vivo action of rosuvastatin in reducing cerebral parasitic load and indicate that this drug may interfere in chronic toxoplasmosis.

Evaluation of the applicability of BI-RADS® MRI for the interpretation of contrast-enhanced digital mammography. / Evaluación de la aplicabilidad del léxico BI-RADS® de la resonancia magnética para la interpretación de la mamografía digital con contraste.

OBJECTIVE: To determine the usefulness of BI-RADS® MRI for the morphological description and categorization of images obtained with contrast-enhanced digital mammography in comparison with the final diagnosis. MATERIAL AND METHODS: We included patients who had palpable breast lesions, those who needed clarification regarding abnormalities identified with another imaging technique, and those which needed a complementary evaluation of heterogeneously dense breast parenchyma. Three radiologists working independently used a template with the BI-RADS® MRI qualitative descriptors to evaluate the breast lesions studied with contrast-enhanced digital mammography. In a second phase, two other experienced radiologists reached a consensus about discrepant interpretations. Readers also classified each lesion (both benign and malignant lesions) on the BI-RADS® scale (1 - 5). All the results were compared with the real state of disease (determined by the appropriate gold standard for each type of lesion), and the statistical significance was assessed with the chi-square test. RESULTS: A total of 218 benign lesions and 426 malignant lesions were included. The interobserver agreement among the three radiologists was high (Fleiss-Cohen kappa=0.805; 95% CI: 0.728-0.837). Similarly to what has been reported about breast MRI, on contrast-enhanced digital mammography, malignant lesions with mass effect tended to have an irregular shape with spiculated or ill-defined margins and a pattern of intense and heterogeneous enhancement (p <0.001). Nevertheless, unlike on breast MRI, ring enhancement was not an independent criterion of malignancy on contrast-enhanced digital mammography. For lesions without a mass effect, the only significant descriptor was the intensity of contrast material uptake (p <0.05). Applying the BI-RADS® MRI material to contrast-enhanced digital mammography images enabled the correct classification of 85% of lesions in the benign categories (BI-RADS 1 and BI-RADS 2 and 3 lesions) and of 93% of the lesions in the malignant categories (BI-RADS 4-5); these values are similar to those reported for breast MRI. CONCLUSIONS: The morphological descriptors used in BI-RADS® MRI can be applied to the morphological analysis of breast lesions studied with contrast-enhanced digital mammography. The partial discrepancies in the interpretation did not influence the final BI-RADS® score, and the score enabled good differentiation between benign and malignant lesions.

Factors affecting the precision of lesion sizing with contrast-enhanced spectral mammography.

AIM: To evaluate the precision of the pre-surgical measurement of the size of breast cancer by contrast-enhanced spectral mammography (CESM). MATERIAL AND METHODS: This was a retrospective study of 204 breast cancers. Variables related to tumour biology and anthropometric variables were recorded and considered when evaluating the efficacy of CESM in predicting tumour size. Microscopic measurement of the largest diameter of the tumour at pathology was chosen as the reference standard. RESULTS: The mean size of tumours at pathology was 20.7±15.8 mm, while at CESM it was 23.6±16.7 mm (Bland-Altman 2.9 mm overestimation, 2.9 mm; 95% confidence interval [CI]: -10.3-16.2 mm). Spearman's correlation coefficient was 0.83 (p<0.0001). The concordance analysis indicated that 37.8% of the measurements were concordant, 47% were overestimated, and 15.2% were underestimated. Tumour size, nodal involvement, breast density, and breast size significantly modified the sizing accuracy. CONCLUSION: Quality of tumour size prediction with CESM is good, and this appears to be a promising imaging technique in the surgical planning of breast cancer. Biological tumour features, and anthropological characteristics of the patients do, however, affect the diagnostic precision and should be taken into account.

Conservation and chemical composition of Leucaena leucocephala plus fresh or wilted Pennisetum purpureum mixed silages / Conservación y composición de ensilajes mixtos de Leucaena leucocephala con Pennisetum purpureum fresco o presecado

Objective. Quantify the effects of mixing Leucaena (L) with King grass forage, fresh (K) or wilted (Kp), on the fermentation process and chemical composition of mixed silages. Materials and methods. Silos were produced mixing several proportions (kg:kg) K:L and Kp:L (100:0; 75:25; 60:40; 50:50; 40:60 and 0:100) of both types of plants, under a completely randomized design of four replications. The quantity of organic acids (butyric, acetic, lactic), pH, ammonia nitrogen percent and some of the typical bromatologic nutrients of the forage before and after ensiling were measured. The treatment effects were evaluated through variance and regression analysis. Results. The results clearly proved the differences (p<0.05) between King grass and Leucaena which promote its mixing and wilting: better legume contents of crude protein (24 vs. 7%), dry matter (33.77 vs. 22.05%) and crude fiber (26.53 vs. 32.5%). Clear benefits on the conservation process of mixed silages were also measured: higher lactic productions and less butyric, acceptable pH (4.02-4.8) and protein degradation (<8%). In addition, a positive effect on the chemical composition of the aforementioned silages was quantified (crude protein, dry matter and crude fiber progressive improvement). Conclusions. Mixed K+L silages are better than pure K if L is included below 25% in KL and up to 40% when K has been wilted. Higher inclusions of L will worsen the conservation process and will limit its elaboration.

Objetivo. Cuantificar los efectos de la adición de forraje de Leucaena leucocephala (L) en el proceso fermentativo y la composición química de ensilajes mixtos con King grass fresco (K) o presecado (Kp). Materiales y métodos. Se ensilaron en condiciones de laboratorio diferentes proporciones (kg:kg) K:L y Kp:L (100:0; 75:25; 60:40; 50:50; 40:60 y 0:100), bajo un diseño totalmente al azar de cuatro repeticiones por cada una. Se midió la cantidad de ácidos orgánicos (butírico, acético, láctico), pH, porcentaje de nitrógeno amoniacal y los nutrientes típicos de la bromatología en el forraje antes de ensilar y en los ensilados resultantes. Los efectos de los tratamientos se midieron mediante análisis de varianza y regresión. Resultados. Los resultados demostraron las diferencias (p<0.05) de la composición química entre el King grass y la Leucaena que animan a su deshidratación previa y mezclado: mejores tenores de proteína cruda (24 vs. 7%), de materia seca (33.77 vs. 22.05%) y fibra cruda (26.53 vs. 32.5%) en la leguminosa; así como los beneficios en la preservación del ensilaje mixto (mejores producciones de ácido láctico y menores del butírico, aceptable pH (4.02-4.8) y degradación de la proteína(<8%) y en la bromatología de estos (avance progresivo en la concentración de proteína, materia seca y fibra). Conclusiones. Los ensilajes mixtos K+L son mejores que los de K siempre que L se adicione hasta 25% con K y hasta 40% con K presecado. Con inclusiones mayores de Leucaena se empeora la conservación, lo que limita su elaboración.

Evaluation of apoptosis as a mechanism of follicular cell atresia in the ovaries of cattle (bos indicus) and buffalo (bubalus bubalis) fetuses

The objective of this study was to investigate the occurrence of apoptosis in the ovaries of cattle and buffalo fetuses between 4 and 8 months old by the terminal deoxynucleotidyltransferase - mediated dUTP nick end labeling (TUNEL) assay . Histological analysis of the ovarian t issue showed that apoptosis occurred at all ages evaluated , presenting a similar pattern among different fetal stages in both species . Within species, secondary follicles displayed a higher (P 0.05) of apoptotic follicular cells among the three follicular classes compared . C omparing resul ts between species, secondary follicles had a higher (P < 0.05) mean number of TUN EL positive cells in bovine fetuses; however , this difference was proportional to the larger number of follicular cells present in secondary follicles in this species . In summary, the TUNEL method was effective for the detection of apoptosis in the support ing cells of ovarian follicles from bovine and buffalo fetuses with apoptosis occurring at similar rates in both species between 4 and 8 months of gestational age. Further studies are needed to better understand the dynamics of apoptosis as a regulator of follicular atresia in fetal ovaries from these species, as well as the potential involvement of the oocyte in this process.

[Assessment of nutritional interventions and hygiene and health habits in a cohort of primary school students]. / Evaluación de dos intervenciones nutricionales y de hábitos de higiene y salud en una cohorte de alumnos de enseñanza primaria.

OBJECTIVE: To quantify by means of the so-called "Healthy lifestyle pyramid" and after two educational interventions, the changes in food intake, daily activities, and hygiene and health habits in the short and long terms in a cohort of healthy children. MATERIALS AND METHOD: prospective longitudinal study with baseline assessment of dietary and lifestyle habits, and two assessments after two educational interventions. RESULTS: 52 children participated, mean age 7.9 years, 15.4% of them being obese. There was a statistically significant reduction in whole milk intake in both the short and long term. There was a significant decrease in the short term in the intake of processed cold meat and an increase in fruit intake. There was a significant reduction in sweets intake in the short term. There was a statistically significant change in hand washing in the short and long terms, as well as in beach bathing after eating. There also was a significant change in achieving an appropriate posture and not bathing too far away, both in the long run. Finally, there was a significant change in the short term in not using inappropriate sports playing fields. The frequency at which they practise sports in the long term was significantly increased as well as the number of weekly sports, in the short term. CONCLUSIONS: After two educational interventions, the children did significant modifications of their health habits in the short term or the long term, which contributes to modify the risk factors for disease in the adulthood.

Effect of nationwide tobacco control policies on smoking cessation in high and low educated groups in 18 European countries.

BACKGROUND: Recently a scale was introduced to quantify the implementation of tobacco control policies at country level. Our study used this scale to examine the potential impact of these policies on quit ratios in European countries. Special attention was given to smoking cessation among lower educational groups. METHODS: Cross-sectional data were derived from national health surveys from 18 European countries. In the analyses we distinguished between country, sex, two age groups (25-39 and 40-59 years) and educational level. Age-standardised quit ratios were calculated as total former-smokers divided by total ever-smokers. In regression analyses we explored the correlation between national quit ratios and the national score on the Tobacco Control Scale (TCS). RESULTS: Quit ratios were especially high (>45%) in Sweden, England, The Netherlands, Belgium and France and relatively low (<30%) in Lithuania and Latvia. Higher educated smokers were more likely to have quit smoking than lower educated smokers in all age-sex groups in all countries. National score on the tobacco control scale was positively associated with quit ratios in all age-sex groups. The association of quit ratios with score on TCS did not show consistent differences between high and low education. Of all tobacco control policies of which the TCS is constructed, price policies showed the strongest association with quit ratios, followed by an advertising ban. CONCLUSION: Countries with more developed tobacco control policies have higher quit ratios than countries with less developed tobacco control policies. High and low educated smokers benefit about equally from the nationwide tobacco control policies.

The inducible isoform of CREM (inducible cAMP early repressor, ICER) is a repressor of CYP19 rat ovarian promoter.

The synthesis of estradiol by the granulosa cells is a prominent event in ovarian physiology and depends on the expression of P450(AROM). FSH induces the expression of P450(AROM) in granulosa cells as a result of the presence in the ovarian promoter of a CRE (cAMP response element)-like sequence (CLS). In rodents, LH downregulates aromatase expression during luteinization by an as yet undescribed mechanism. In granulosa cells, LH increases the expression of the inducible cAMP early repressor (ICER), an isoform of CREM (cAMP-responsive element modulator) that represses cAMP-induced transcription. The possibility that ICER represses the activity of the aromatase ovarian promoter, thus being part of the mechanism underlying the effects of LH was investigated. We have found that: (1) nuclear proteins from forskolin-stimulated granulosa cells were specifically bound to an oligonucleotide containing the CLS sequence of the CYP19 ovarian promoter and one out of the two protein-DNA complexes formed was supershifted by an anti-CREM antibody; (2) in granulosa cells, forskolin-induced increases in P450(AROM) promoter luciferase reporter gene activity were prevented by the transient overexpression of ICER; (3) similar results were obtained in 8-Br-cAMP-stimulated R2C cells, a Leydig tumor cell line routinely used for the study of P450(AROM) promoter activity; (4) both ICER mRNA levels and P450(AROM) promoter-driven luciferase activity were elevated 6 and 12 h after stimulation of R2C cells with 8-Br-cAMP and were decreased 24 and 48 h later; (5) in an R2C polyclonal line overexpressing ICER, the promoter activity at early stages of stimulation was completely attenuated, while 24 and 48 h downregulation was prevented in another R2C line stably transfected with an antisense ICER construct. These results suggest that ICER represses CYP19 ovarian promoter and that LH-induced expression of ICER may serve to downregulate P450(AROM) transcription in granulosa cells during luteinization.

[Evolution of mortality attributable to tobacco in the Canary Islands (1975-1994)]. / Evolución de la mortalidad atribuible al tabaco en las Islas Canarias (1975-1994).

BACKGROUND: The objective of this study is that of describing the death rate attributable to tobacco on the Canary Islands throughout the 1975-1994 period. METHOD: Deaths by age, sex and cause from 1975 to 1994 were obtained from the Spanish National Institute of Statistics (Natural Movement of Population). Based on the Spanish and Canary Island Health Surveys, the percentages of those who had never smoked, smokers and ex-smokers for the Canary Island population were taken by age and sex. The relative risks of death were taken from the Cancer Prevention Study II carried out in the United States. The percentages of deaths attributable to smoking were calculated for each year, sex and age group based on the attributable fraction of the population. Likewise, the trend in the death rate attributable for the time period in question was calculated and given in the form of the annual mean percentage change in the age-adjusted death rates by way of a log-linear model. RESULTS: During the 1975-1994 period, the number of deaths attributed to smoking rose by 64%. For major causes, a 108% increase in neoplasias, a 32% drop in cardiovascular diseases and a 15.5% increase in respiratory diseases were found for the period under study. The number of deaths was also found to increase with age, the 65 and over age group having been found to be that in which the most deaths caused by smoking occurred. CONCLUSIONS: On the Canary Islands, over 20% of all deaths in 1994 can be attributed to smoking. This suggests that the measures implemented to control the smoking habit are insufficient.

[Mortality and quality of life of patients beyond 65 years one year after ICU discharge]. / Mortalidad y calidad de vida al año del alta de una unidad de cuidados intensivos en pacientes mayores de 65 años.

BACKGROUND: Intensive care in elderly patients is a subject of controversy, because they generally present a high rate of mortality and short expectation of life. Due to the increasing life expectancy, more elderly patients will be treated in Intensive Care Unit (ICU) with an increasing consume of resources. The present study considers the mortality and quality of life (QOL) of patients beyond 65 years after ICU, and theirs predictors. PATIENTS AND METHOD: Retrospective study of patients >= 65 years admitted in multidisciplinaire ICU. Mortality and QOL (with modified EuroQOL Instrument) one year after discharge were studied. To determine mortality and QOL one year independent predicting factors, multiple logistic regression models were used. RESULTS: Of 313 patients studied, 95 (30%) died in ICU, 32 (10%) in hospital and 34 (11%) died after discharge. The independent predicting factors of mortality one year after ICU discharge were: organ failure (p < 0.000; odds ratio [OR], 2.9), cardiac surgery (p < 0.0000; OR, 0.15) and respiratory disease (p < 0.01; OR, 2.8). Of the 152 surviving patients, 21% got worse their previous QOL and only 17% were severely discapitated. The independent predicting factors of QOL one year after ICU discharge were: prior QOL (p < 0.0002; OR, 10.2) and age (p < 0.002; OR, 0.09). CONCLUSION: Despite the high one year after ICU discharge mortality rate (51%), 83% of the survivors were able to live independently. Due to dependence between mortality and multiorganic failure during ICU stay and not age, this latter cannot be the determining factor of the care level.

Acute cholecystitis: video-laparoscopic versus traditional treatment.

It has been shown that a video-laparoscopic approach is the preferred method for treatment of cholecystitis. However, when we consider acute cholecystitis, many questions must be answered. The aim of this study is to compare video-laparoscopic and conventional surgery in the management of acute cholecystitis.

Regulation by ceramide of epidermal growth factor signal transduction and mitogenesis in cell lines overexpressing the growth factor receptor.

Ceramide has emerged as a pleiotropic signal mediator of cellular responses including differentiation, proliferation, cell cycle arrest and apoptosis. In the present study we evaluated the effect of cell permeant ceramide analogues on ligand-induced tyrosine phosphorylation of the EGF receptor (EGFR), phospholipase Cy (PLCgamma) activity and cell proliferation. Treatment with N-acetylsphingosine (C2-cer) and N-hexanoylceramide (C6-cer) prevented EGF-induced tyrosine trans-phosphorylation of the receptor in two different cell lines overexpressing the human EGFR (A431 and EGF-T17 cells). In contrast, treatment of A431 and EGFR-T17 cells with C2-cer or C6-cer did not affect the ligand binding capacity of the receptor, an effect that was however observed after TPA-induced activation of PKC. In addition EGF-stimulated PLCgamma activity was transiently decreased in A431 cells treated with C6-cer and only a modest, albeit significant reduction on ligand-induced 3H-InsP3 generation was observed in EGFR-T17 cells pretreated with ceramide. We also examined the effect of C2-cer on serum (A431)- or EGF (EGFR-T 17)-induced cell proliferation. Treatment of EGFR-TI7 cells with C2-cer (0.1-10 microM) did not affect cell viability, but prevented EGF-induced 3H-thymidine incorporation in a dose-dependent manner. In contrast, 3H-thymidine incorporation in serum-stimulated A431 cells decreased only at the higher doses of C2-cer used (1-10 microM), being this effect accompanied by a slight, albeit significant (20-25%), reduction in cell viability.

[Survival and quality of life of patients with multiple organ failure one year after leaving an intensive care unit]. / Supervivencia y calidad de vida de los pacientes con fracaso multiorgánico al año del alta de una unidad de medicina intensiva.

BACKGROUND: The patients' mortality with multiple organ failure (MOF) is very high and patients who consume the most resources are those with uncertain prognosis. In order to use the limited resources adequately, it is necessary to know the cost-benefit relationship of their treatment and in this study cost, mortality, quality of life (QOL) of survivors who developed MOF has been investigated. PATIENTS AND METHODS: Mortality in the Intensive Care Unit (ICU) and mortality QOL (with modified EuroQOL Instrument) one year after discharge were studied in 239 admitted patients who developed MOF. Cost was estimated from administrative dats of cost patients-day. To determine mortality independent predicting factors, a logistic regression model was used. RESULTS: Of the 239 patients studied, 144 (60%) died in ICU and 29 (12%) died after discharge. The independent predicting factors of mortality one year after discharge from ICU were: age (p < 0.1, odds ratio [OR] = 1.02), cardiac surgery (p < 0.0000, OR = 0.1899) and trauma (p < 0.05, OR = 0.2287). Of the 66 surviving patients, 18% were severely discapacitated. Forty one percent recovered their previous QOL, 18% improved it and 39% got worse. Patients with MOF consumed 64% of ICU total resources and of these, 77% was consumed by patients who died and by severely discapacitated. CONCLUSION: A high proportion of resources were used by MOF patients, but patients who died and who remained with worst QOL consumed the highest part. Although the mortality after one year was high (72%), 80% of the survivors achieved an acceptable QOL and for this reason, treatment of these patients should not be limited if survival and QOL predictions are not 100% correct.

Videolaparoscopic approach of the splenic cyst: a case report.

The authors report a case of an asymptomatic 30-year-old female patient with an extensive cystic lesion continuous with the splenic parenchyma. A review of the literature and use of a videolaparoscopic approach to the treatment of these lesions is presented.

Non-traumatic acute abdomen: videolaparoscopic approach.

BACKGROUND AND OBJECTIVE: Although videolaparoscopy has been considered a safe method for many elective procedures, its use in traumatic and non-traumatic acute abdomen needs to be evaluated. The aim of this article is to evaluate the role of videolaparoscopy in non-traumatic acute abdomen as a method of diagnosis and treatment. METHODS: Between January 1992 and December 1996, 462 patients' charts were reviewed, retrospectively. Patients were admitted to the emergency room of São Rafael Hospital with symptoms of non-traumatic acute abdomen. Routine investigation of abdominal pain was performed in all patients, followed by videolaparoscopy. The laparoscopic procedures were done with four main purposes: diagnosis (ie, enteritis); diagnosis and treatment (ie, appendicitis); treatment only, when the diagnosis was known (ie, acute cholecystitis); and in cases where the conversion to conventional laparotomy was necessary, indicating the best incision. RESULTS: The vast majority of patients had inflammatory causes of acute abdomen (82.03%); others causes were hemoperitoneum (11.03%), bowel obstruction (3.25%), perforation of a hollow viscera (1.74%), vascular occlusion (1.3%), and negative laparoscopy (0.65%). CONCLUSIONS: This study shows that laparotomy was necessary in only 7.14% of the patients. The videolaparoscopic approach was used for diagnosis (99.35%) and treatment (92.86%) of patients with acute abdomen.