14-3-3ε protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity.

Adipose-derived mesenchymal stem cells (ASCs) accelerate the osteointegration of bone grafts and improve the efficiency in the formation of uniform bone tissue, providing a practical and clinically attractive approach in bone tissue regeneration. In this work, the effect of nanofibrous biomimetic matrices composed of poly(ε-caprolactone) (PCL), nanometric hydroxyapatite (nHA) particles and 14-3-3 protein isoform epsilon on the initial stages of human ASCs (hASCs) osteogenic differentiation was investigated. The cells were characterized by flow cytometry and induction to differentiation to adipogenic and osteogenic lineages. The isolated hASCs were induced to differentiate to osteoblasts over all scaffolds, and adhesion and viability of the hASCs were found to be similar. However, the activity of alkaline phosphatase (ALP) as early osteogenic marker in the PCL-nHA/protein scaffold was four times higher than in PCL-nHA and more than five times than the measured in neat PCL.

In vivo measurements of electrical conductivity of porcine organs at low frequency: new method of measurement.

Calculations of the induced currents created in the human body by external electromagnetic fields would be more accurate provided that more realistic experimental values of the electrical properties of the body were available. The purpose of this work is to experimentally obtain values for the conductivity of living organs in conditions close to the real situation. Two-electrode in vivo measurements of the bioimpedance of some porcine organs have been performed. From these measurements and taking into account geometrical considerations, the electrical conductivity for the kidney, liver, heart, and spinal cord has been obtained and were found to be higher than the values reported in the literature. Furthermore, a new experimental procedure is proposed where the conductivity is determined from the values of the electrical potential and currents that are induced by an external electromagnetic field created by a coil placed close to the organ under study.

The role of emulsion parameters in tramadol sustained-release from electrospun mats.

Tramadol is an analgesic usually prescribed for the management of pain, with a certain risk of addiction in chronic patients. The incorporation of tramadol in sustained-release systems results particularly attractive for the administration of accurate doses. In this work, emulsion electrospinning was used for the preparation of tramadol-loaded nanofibrous membranes based on poly(ε-caprolactone). Compositional and processing parameters were screened and evaluated in terms of the morphology of the resulting nanofibers, encapsulation efficiency and drug release in time. The polymer concentration, surfactant type and amount, and the homogenization rate used for the emulsions preparation were found to greatly affect the fluid stability and the resulting materials structure and functionality. The intrinsic features of the starting fluid studied in this work played a significant role for the modulation of tramadol release from nanofibrous matrices. The use of sodium dodecyl sulfate as surfactant with an optimal homogenization rate allowed the preparation of electrospun fibrous membranes with good encapsulation efficiency, a minimal burst release and a sustained delivery of tramadol in time.

Spontaneous remission in diffuse large cell lymphoma: a case report.

BACKGROUND: Spontaneous remission in solid malignancies has been documented. However, spontaneous remission in aggressive diffuse large b cell lymphoma is exceedingly rare. Previous reports of lymphoma remission suggest that not yet fully characterized tumor-intrinsic and microenvironment mechanisms cooperate with spontaneous regression. CASE DESCRIPTION: Here, we report the case of an 88-year-old white woman with diffuse large b cell lymphoma (follicular lymphoma transformed) who achieved morphologic spontaneous remission 3 months after her diagnostic core biopsy. We examined 16 similar cases of diffuse large b cell lymphoma suggesting that spontaneous remission is preferentially observed in elderly patients soon after their biopsy microtrauma, especially if malignancies are Epstein-Barr virus driven and activated B-cell type. CONCLUSION: Our case and reported analysis highlight that anti-tumor adaptive T cell responses are potentially augmented in a subset of patients leading to lymphoma regression. In these patients, it is possible that "primed" innate anti-tumor T cell immunity is enhanced in immunogenic lymphoma subtypes after tissue biopsy. Our case and analysis not only reinforce the role of innate T cell anticancer immunity, but also originates potential proof of concept for investigation of unexplored pathways that could favorably impact T cell therapy.

Exercise prescription in patients with cirrhosis: Recommendations for clinical practice. / Prescripción de ejercicio en pacientes con cirrosis: recomendaciones para la atención clínica.

Exercise in cirrhosis of the liver is an emerging topic in hepatology. Despite the known benefits of exercise in the general population, there are currently few studies addressing that issue in relation to cirrhosis and more evidence is still needed. Even though some studies have reported an acute, exercise-induced increase in the hepatic venous pressure gradient (HVPG), the opposite (a decrease in the HVPG) has been shown by recent data after an exercise program carried out for>14 weeks. In addition to that benefit, improvement has been described in the metabolic profile, quality of life, muscle mass, cardiopulmonary function, and nutritional status. Together, those features make exercise in cirrhosis a very attractive intervention. However, certain aspects must be taken into account before prescribing exercise in that population and they include cardiovascular risk, musculoskeletal disorders, and complications related to cirrhosis. After considering those factors, an individually tailored exercise program should be developed for each patient, according to the points stated above and the desired goal. Information about exercise-limiting factors, type of exercise prescribed, monitoring methods, and concomitant nutritional therapy is provided in the present review.

Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers.

Opiate addiction is a chronic medical disorder characterized by drug tolerance and dependence, behavioral sensitization, vulnerability to compulsive relapse, and high mortality. In laboratory animals, the potential effect of opiate drugs to induce cell death by apoptosis is a controversial topic. This postmortem human brain study examined the status of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of a large group of well-characterized heroin or methadone abusers. In these subjects (n=36), the immunocontent of apoptosis-1 protein (Fas) death receptor did not differ from that in age-, gender-, and postmortem delay-matched controls. In contrast, Fas-associated protein with death domain (FADD), the mediator of the death signal, was significantly decreased in the same brain samples (all addicts: 30%, n=36; short-term abuse (ST): 31%, n=15; long-term abuse (LT): 29%, n=21). The initiator caspase-8 was not altered, but FLIP(L) (Fas-associated protein with death domain-like interleukin-1beta-converting enzyme-inhibitory protein), a dominant inhibitor of caspase-8, was increased in LT addicts (19%). In the intrinsic pathway, the pro-apoptotic mitochondrial proteins Bax (Bcl-2-associated X protein) and AIF (apoptosis-inducing factor) remained unchanged, but cytochrome c was decreased (all addicts: 25%; ST: 31%; LT: 20%) and anti-apoptotic B-cell leukemia 2 (Bcl-2) increased in LT addicts (24%). The content of executioner caspase-3 and the pattern of cleavage of the nuclear enzyme poly-(ADP-ribose)-polymerase-1 (PARP-1) were similar in opiate addicts and control subjects. Taken together, the data revealed that the extrinsic and intrinsic canonical apoptotic pathways are not abnormally activated in the prefrontal cortex of opiate abusers. Instead, the chronic modulation of some of their components (downregulation of FADD and cytochrome c; upregulation of FLIP(L) and Bcl-2) suggests the induction of non-apoptotic actions by opiate drugs related to phenomena of synaptic plasticity in the brain. These neurochemical adaptations could play a major role in the development of opiate tolerance, sensitization and relapse in human addicts.

Time dependence of electrical bioimpedance on porcine liver and kidney under a 50 Hz ac current.

The purpose of this work is to study the changes of the bioimpedance from its 'in vivo' value to the values measured in a few hours after the excision from the body. The evolution of electrical impedance with time after surgical extraction has been studied on two porcine organs: the liver and the kidney. Both in vivo and ex vivo measurements of electrical impedance, measuring its real and imaginary components, have been performed. The in vivo measurements have been carried out with the animal anaesthetized. The ex vivo measurements have been made more than 2 h after the extraction of the organ. The latter experiment has been carried out at two different stabilized temperatures: at normal body temperature and at the standard preservation temperature for transplant surgery. The measurements show a correlation between the biological evolution and the electrical bioimpedance of the organs, which increases from its in vivo value immediately after excision, multiplying its value by 2 in a few hours.

Dietary management and supplementation with branched-chain amino acids in cirrhosis of the liver. / Manejo dietético y suplementación con aminoácidos de cadena ramificada en cirrosis hepática.

One of the most important characteristics of malnutrition is the loss of muscle mass and the severe depletion of the protein reserve, secondarily affecting energy metabolism. That impacts nutritional status and the progression of disease-related complications. Nutritional treatment is one of the main factors in the comprehensive management of those patients. Achieving adequate energy intake that provides the macronutrients and micronutrients necessary to prevent or correct malnutrition is attempted through dietary measures. ESPEN, the European Society for Clinical Nutrition and Metabolism, recommends a caloric intake of 30-40kcal/kg/day, in which carbohydrates provide 45-60% of the daily energy intake and proteins supply 1.0-1.5g/kg/day. The remaining portion of the total energy expenditure should be covered by lipids. The administration of branched-chain amino acids has been shown to be beneficial not only in counteracting malnutrition, but also as a coadjuvant treatment in specific complications, thus playing a favorable role in outcome and quality of life. Therefore, branched-chain amino acids should be considered part of nutritional treatment in patients with advanced stages of cirrhosis of the liver, particularly in the presence of complications.

Role of activator protein-1 on the effect of arginine-glycine-aspartic acid containing peptides on transforming growth factor-beta1 promoter activity.

While arginine-glycine-aspartic acid-based peptidomimetics have been employed for the treatment of cardiovascular disorders and cancer, their use in other contexts remains to be explored. Arginine-glycine-aspartic acid-serine induces Transforming growth factor-beta1 transcription in human mesangial cells, but the molecular mechanisms involved have not been studied extensively. We explored whether this effect could be due to Activator protein-1 activation and studied the potential pathways involved. Addition of arginine-glycine-aspartic acid-serine promoted Activator protein-1 binding to its cognate sequence within the Transforming growth factor-beta1 promoter as well as c-jun and c-fos protein abundance. Moreover, this effect was suppressed by curcumin, a c-Jun N terminal kinase inhibitor, and was absent when the Activator protein-1 cis-regulatory element was deleted. Activator protein-1 binding was dependent on the activity of integrin linked kinase, as transfection with a dominant negative mutant suppressed both Activator protein-1 binding and c-jun and c-fos protein increment. Integrin linked kinase was, in turn, dependent on Phosphoinositol-3 kinase activity. Arginine-glycine-aspartic acid-serine stimulated Phosphoinositol-3 kinase activity, and Transforming growth factor-beta1 promoter activation was abrogated by the use of Phosphoinositol-3 kinase specific inhibitors. In summary, we propose that arginine-glycine-aspartic acid-serine activates Integrin linked kinase via the Phosphoinositol-3 kinase pathway and this leads to activation of c-jun and c-fos and increased Activator protein-1 binding and Transforming growth factor-beta1 promoter activity. These data may contribute to understand the molecular mechanisms involved in the cellular actions of arginine-glycine-aspartic acid-related peptides and enhance their relevance as these products evolve into clinical therapeutic use.

Gelatinous Marrow Transformation Associated with Imatinib: Case Report and Literature Review.

Gelatinous marrow transformation (GMT) is a rare condition observed in severe illness or malnutrition, in which the bone marrow contains amorphous "gelatinous" extracellular material, and histopathology demonstrates varied degrees of fat cell atrophy and loss of hematopoietic elements. An association of GMT with imatinib use in chronic myeloid leukemia (CML) has been reported recently. The objective of this study is to describe a case of GMT associated with imatinib use and review the existing similar cases in the literature to identify epidemiological patterns and potential imatinib-induced mechanisms leading to gelatinous conversion.

[Renal aging]. / Envejecimiento renal.

Frequently underestimated, the deterioration of the renal function characteristic of the aging has very prominent clinical consequences. In the present article some aspects of the cellular and molecular biology of this process are analysed. The critical role of the oxidative stress and of TGFbeta are underlined. Determinant genetic factors are also mentioned. Such a knowledge can contribute to develop therapeutical strategies to prevent the decline of the.renal function that happens with the aging.

Angiotensin II induces a rapid and transient increase of reactive oxygen species.

Vascular smooth muscle cells (VSMC) exhibit a hypertrophic and contractile response after angiotensin II (Ang II) treatment, and the NADH/NADPH oxidase-dependent synthesis of hydrogen peroxide (H(2)O(2)) seems to play a central role in these responses. Present experiments were designed to analyze the mechanisms responsible for the rapid changes induced by Ang II in the intracellular H(2)O(2) concentration in VSMC. Ang II induced a quick and transient increase of dichlorodihydrofluorescein (DCHF) fluorescence in VSMC, an effect that was completely abolished by catalase and by diethyldithiocarbamate, a cell-permeable superoxide dismutase inhibitor. Losartan and pertussis toxin prevented the stimulatory effect of Ang II. Both diphenylene iodonium (NADH/NADPH oxidase blocker) and 3-(4-octadecylbenzoyl)acrylic acid (phospholipase A2 blocker) inhibited the changes in DCHF fluorescence induced by Ang II, in a dose-dependent fashion, and the effects of both inhibitors were additive. These data demonstrate that Ang II induces a very quick and transient increase of H(2)O(2) in VSMC. This effect depends on the receptor type 1, is linked to a G protein, and involves both NADH/NADPH oxidase and phospholipase A2 activation. The mechanism may be related to the previously proposed role of H(2)O(2) in the genesis of the Ang II-induced cell contraction.

Listeria monocytogenes infection in patients with cancer.

Listeriosis (LT) is an important infection in immunocompromised patients, but no large series of LT in cancer patients have been recently described. We reviewed the records of 34 cancer patients with LT at our institution (1990-2001). Twenty patients (59%) had an underlying hematologic malignancy. In 11 patients, LT complicated bone marrow transplantation. Lymphocytopenia was observed in 62% of the patients. Twenty-six patients (76%) received prior corticosteroids. Bacteremia was the most common presentation of LT (74%) followed by meningoencephalitis (21%). The most common treatment of LT was ampicillin with or without gentamicin (68%). The median duration of treatment was 26 days (range, 8-74 days). The rate of response to antimicrobial therapy was 79%. No relapses were identified. LT contributed to death in 9 (75%) of the 12 patients who died. Meningoencephalitis had the worst prognosis (3 of 6 cases were fatal). Treatment of central nervous system LT continues to have a high failure rate.

Brain RGS4 and RGS10 protein expression in schizophrenia and depression. Effect of drug treatment.

RATIONALE: Regulator of G-protein signaling (RGS) proteins, RGS4 and RGS10, may be involved in the pathophysiology of schizophrenia. RGS4 has attracted special interest since the reports of genetic association between SNPs in RGS4 and schizophrenia. However, there is no information about the subcellular distribution of RGS4 and RGS10 proteins in psychiatric disorders. OBJECTIVES: Plasma membrane RGS4 and cytosolic RGS10 protein immunoreactivity in prefrontal cortex from schizophrenic subjects (n = 25), non-diagnosed suicides (n = 13), and control subjects (n = 35), matched by age, gender, and postmortem delay, was analyzed by western blot. A second group of depressed subjects (n = 25) and control subjects (n = 25) was evaluated. The effect of the antipsychotic or antidepressant treatments was also assessed. RESULTS: No significant differences in plasma membrane RGS4 and cytosolic RGS10 protein expression were observed between schizophrenic subjects, non-diagnosed suicides, and control subjects. However, RGS4 immunoreactivity was significantly higher (Δ = 33 ± 10 %, p < 0.05) in the antipsychotic-treated subgroup (n = 12) than in the antipsychotic-free subgroup (n = 13). Immunodensities of plasma membrane RGS4 and cytosolic RGS10 proteins did not differ between depressed and matched control subjects. CONCLUSIONS: Expression of RGS4 and RGS10 proteins at their predominant subcellular location was studied in the postmortem brain of subjects with psychiatric disorders. The results suggest unaltered membrane RGS4 and cytosolic RGS10 proteins levels in schizophrenia and major depression. Antipsychotic treatment seems to increase membrane RGS4 immunoreactivity. Further studies are needed to elucidate RGS4 and RGS10 functional status.

Maltrato juvenil en discapacitados intelectuales, su relación con la comorbilidad psiquiátrica / Juvenile abuse in intellectual disability, its relationship with psychiatric co-morbidities

Children and teenagers with intellectual disability are a complex issue within the society and for the medical practice. Determining the more frequent forms of abuse, it's behaving in this particular population, and to evaluate the possible relationship between juvenile abuse and psychiatric co-morbidities were the main objectives in this investigation. 99 people with intellectual disability between 5 and 17 year old from three different communities (Felicia, Cocosol and Belen) located at Marianao municipality were selected by monoetapic conglomerate and studied firstly trough an analytic study with transversal cut seconded by a differentiated intervention according with the results. Taking into account the sociopsychiatric history, the psychiatric examination, using strictest observational techniques of the patient at home and the school, and applying the tools for diagnosis of infant abuse in this people, we concluded that juvenile abuse was a serious health problem in the studied population: negligence and carelessness the main types. The relationship between infant abuse and psychiatric co-morbities was demonstrated.

La condición de discapacidad intelectual convierte a niños y adolescentes en población de alta complejidad en la medicina. Determinar comportamiento y formas más frecuentes del maltrato en esta población, así como evaluar la relación entre maltrato infantil y comorbilidad psiquíatrica, fueron los objetivos fundamentales de esta investigación. Para ello se estudió una muestra de 99 pacientes discapacitados intelectuales en edades comprendidas entre 5 y 17 años de tres consejos populares (Felicia, Cocosol y Belén) del municipio Marianao, seleccionados por conglomerado monoetápico. Se realizó un estudio analítico de corte transversal en un primer momento, con intervención diferenciada según los resultados en un segundo momento. Mediante la historia socialpsiquíatrica, examen psiquiátrico, empleo de técnicas observacionales rigurosas del paciente en la casa y escuela y aplicación de instrumento para el diagnóstico de maltrato infantil en este tipo de población. Concluimos que el maltrato infantil fue un problema de salud en la muestra estudiada; el maltrato por negligencia o descuido fueron los más frecuentes. Se comprobó estrecha relación entre la existencia de maltrato infantil y comorbilidad psiquiátrica en los pacientes estudiados.

[Epidemiologic considerations on infant mortality in Andalusia, Spain, 1956-1976]. / Consideraciones epidemiológicas de la mortalidad infantil en Andalucía-España, durante el periodo 1956-1976.

PIP: An international comparison of infant mortality rates demonstrates why infant mortality is regarded as the single best indicator of the economic, social, and health conditions of a given community. In 1971 infant mortality rates in Sweden, Holland, and Spain were 11.1, 12.1, and 25.2/1000 live births respectively, while by 1977 they had declined to 8, 9.5, and 16.6. Causes of infant mortality are classified into 2 categories for epidemiological study: endogenous causes related to hereditary factors, congenital anomalies, and accidents during birth cause the majority of deaths in the 1st 28 days, and exogenous or environmental causes account for most postneonatal deaths from the 29th day to the end of the 1st year. Countries which have improved their infant mortality rates have done so primarily by controlling exogenous causes of death. In Andalusia, infant mortality declined from 47.1/1000 live births in 1956 to 19.1 in 1976, a drop of 59.45%. During the same time, neonatal mortality declined by only 24.16%, from 17.8/1000 live births in 1956 to 13.5 in 1976, while postneonatal mortality declined by 80.55%, from 29.3/1000 live births in 1956 to 5.7 in 1976. Nationally, infant mortality declined from 50.9/1000 live births in 1956 to 17.1 in 1976, with Andalusia, Castilla-Leon, and Castilla-La Mancha contributing most to the decline. Neonatal mortality declined by 39.70%, from 19.9/1000 live births in 1956 to 12.0 in 1976 for the nation as a whole, while postneonatal mortality declined by 82.68%, from 30.6 in 1956 to 5.3 in 1976. During the whole period the infant mortality rate in Andalusia was higher than the national average, while in Galicia it was still higher. In 1956, 23.72% of infant deaths were caused by respiratory illnesses, 9.96% by infectious and parasitic diseases, and 3.42% by congenital anomalies, while in 1975, 44.53% were caused by perinatal illness, 21.82% by congenital anomalies, 12.84% by respiratory illness, and 7.86% by infectious and parasitic disease.^ieng