Long-term follow-up of Parkinsonian patients operated on with deep brain electromodulation without intraoperative microrecording.

Background: Deep brain electromodulation (DBEM), also known as deep brain stimulation in different intracerebral targets, is the most widely used surgical treatment due to its effects in reducing motor symptoms of Parkinson's disease. The intracerebral microelectrode recording has been considered for decades as a necessary tool for the success of Parkinson's surgery. However, some publications give more importance to intracerebral stimulation as a better predictive test. Since 2002, we initiated a technique of brain implant of electrodes without micro recording and based solely on image-guided stereotaxis followed by intraoperative macrostimulation. In this work, we analyze our long-term results, taking into account motor skills and quality of life (QL) before and after surgery, and we also establish the patient's time of clinical improvement. Methods: This is a descriptive clinical study in which the motor state of the patients was evaluated with the unified Parkinson's disease scale (UPDRS) and the QL using the Parkinson's disease QL questionnaire 39 questionnaires before surgery, in the "on" state of the medication; and after surgery, under active stimulation and in the "on" state. Results: Twenty-four patients with ages ranging from 37 to 78 years undergoing surgery DBEM on the subthalamic nucleus were studied. An improvement of 41.4% in motor skills and 41.7% in QL was obtained. Conclusion: When microrecording is not available, the results that can be obtained, based on preoperative imaging and clinical intraoperative findings, are optimal and beneficial for patients.

Exploring Vision-Related Quality of Life: A Qualitative Study Comparing Patients' Experience of Cataract Surgery with a Standard Monofocal IOL and an Enhanced Monofocal IOL.

Purpose: To explore quality of life related with intermediate vision of patients before and after cataract surgery, and to make patients' experience available for the design of future scales that assess visual function related with intermediate distance. Patients and Methods: A qualitative research methodology based on thematic content analysis was used to explore vision-related quality of life based on the experiences of patients with cataract. Patients were recruited at the Service of Ophthalmology of the Hospital de Sant Pau (Barcelona, Spain). Data were collected through nineteen semi-structured interviews conducted with patients diagnosed with cataract and implanted with a standard aspheric monofocal intraocular lens (IOL) (Tecnis® ZA9003) (n = 6), an enhanced monofocal IOL (Tecnis® Eyhance ICB000) (n = 6), and patients from the waiting list (n = 7). The data analysis consisted in coding, aggregation, and theme development of the transcribed audios. Results: Patients on waiting lists reported difficulty and insecurity in performing daily and meaningful tasks related to near visual ranges (eg: threading a needle, reading price tags), intermediate (eg: using a computer or dialling numbers on a smartphone), and distant (eg: recognizing faces, walking on uneven surfaces). Patients after surgery with the standard IOL reported improvement in performing activities mainly in the distant visual range, but also the need for a better communication with clinical staff to adjust their own expectations on the results of the surgery. Finally, patients implanted with the enhanced IOL reported satisfaction and improved visual function in performing daily activities, especially those related to the intermediate visual range. Conclusion: Our exploratory study found that patients after cataract surgery with the enhanced IOL reported a better performance in activities that require the intermediate vision. These results will inform the development of scales to assess vision-related quality of life in the intermediate visual range prioritizing outcomes according to patients' daily and meaningful activities.

Improving the genistein oral bioavailability via its formulation into the metal-organic framework MIL-100(Fe).

Despite the interesting chemopreventive, antioxidant and antiangiogenic effects of the natural bioflavonoid genistein (GEN), its low aqueous solubility and bioavailability make it necessary to administer it using a suitable drug carrier system. Nanometric porous metal-organic frameworks (nanoMOFs) are appealing systems for drug delivery. Particularly, mesoporous MIL-100(Fe) possesses a variety of interesting features related to its composition and structure, which make it an excellent candidate to be used as a drug nanocarrier (highly porous, biocompatible, can be synthesized as homogenous and stable nanoparticles (NPs), etc.). In this study, GEN was entrapped via simple impregnation in MIL-100 NPs achieving remarkable drug loading (27.1 wt%). A combination of experimental and computing techniques was used to achieve a deep understanding of the encapsulation of GEN in MIL-100 nanoMOF. Subsequently, GEN delivery studies were carried out under simulated physiological conditions, showing on the whole a sustained GEN release for 3 days. Initial pharmacokinetic and biodistribution studies were also carried out upon the oral administration of the GEN@MIL-100 NPs in a mouse model, evidencing a higher bioavailability and showing that this oral nanoformulation appears to be very promising. To the best of our knowledge, the GEN-loaded MIL-100 will be the first antitumor oral formulation based on nanoMOFs studied in vivo, and paves the way to the efficient delivery of nontoxic antitumorals via a convenient oral route.

Preoperative administration of Omega-3 fatty acids on postoperative pain and acute-phase reactants in patients undergoing Roux-en-Y gastric bypass: A randomized clinical trial.

BACKGROUND: The term "Immunonutrition" (IMN) describes the enteral administration of certain substrates with a theoretical immunomodulating function. From all the elements conforming these IMN formulas, Omega-3 fatty acids (O3FA) are hypothesized to be the most important component for immunomodulation, with increased anti-inflammatory and antioxidant effect. PATIENTS AND METHODS: A prospective randomized clinical trial of all the patients undergoing laparoscopic Roux-en-Y gastric bypass was performed. Patients were randomly assigned into 2 groups: those patients receiving a preoperative balanced energy high-protein formula (Control Group) and those ones who received the same preoperative nutritional formula enriched with O3FA (Experimental Group). In both groups, there was a restriction to 900 Kcal/day. Nutritional intervention started 10 days before surgery and was maintained up to 8 h before the surgical act. Preoperative weight loss, postoperative pain, complications and acute phase reactants were investigated. RESULTS: 40 patients were included in the study, 20 in each group. Preoperative excess weight loss (EWL) with the prescribed treatment was 10.6 ± 7.7% in Control Group and 14.1 ± 5.8% in the Experimental Group (p = 0.024). Mean postoperative pain was 25 ± 9.2 mm in Control group and 10,9 ± 4,4 mm in Experimental Group (p = 0.015). CRP determined 24 h after surgery was significantly lower in the Experimental Group than in the Control Group. There were not significant differences in complications, mortality or readmission rates between groups. CONCLUSIONS: The use of a nutritional supplement enriched with O3FA is associated with a greater preoperative weight loss, reduced postoperative pain and decreased postoperative levels of C reactive protein.

Micro- and nanotechnology approaches to improve Parkinson's disease therapy.

Current therapies for Parkinson's disease are symptomatic and unable to regenerate the brain tissue. In recent years, the therapeutic potential of a wide variety of neuroprotective and neuroregenerative molecules such as neurotrophic factors, antioxidants and RNA-based therapeutics has been explored. However, drug delivery to the brain is still a challenge and the therapeutic efficacy of many drugs is limited. In the last decade, micro- and nanoparticles have proved to be powerful tools for the administration of these molecules to the brain, enabling the development of new strategies against Parkinson's disease. The list of encapsulated drugs and the nature of the particles used is long, and numerous studies have been carried out supporting their efficacy in treating this pathology. This review aims to give an overview of the latest advances and emerging frontiers in micro- and nanomedical approaches for repairing dopaminergic neurons. Special emphasis will be placed on offering a new perspective to link these advances with the most relevant clinical trials and with the real possibility of transferring micro- and nanoformulations to industrial scale-up processes. This review is intended as a contribution towards facing the challenges that still exist in the clinical translation of micro- and nanotechnologies to administer therapeutic agents in Parkinson's disease.

Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus.

INTRODUCTION: Despite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization. METHODS: We conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein-cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months. RESULTS: The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2-12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8-8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms. CONCLUSION: In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.

Alpha Klotho and Fibroblast Growth Factor-23 Among Alcoholics.

AIMS: Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. METHODS: Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry). We measured plasma levels of FGF-23 and serum soluble α Klotho, using ELISA in 97 patients and 20 age- and sex-matched controls. RESULTS: FGF-23 levels were higher in patients than in controls (Z = 3.50; P < 0.001). FGF-23 (Z = 5.03; P < 0.001) and soluble α Klotho (Z = 5.61; P < 0.001) were higher in cirrhotics, and both were related to liver function, independently of serum creatinine FGF-23 levels were higher among alcoholics with diabetes (Z = 2.55; P = 0.011) or hypertension (Z = 2.56; P = 0.01), and increased body fat (ρ = 0.28; P = 0.022 for trunk fat), whereas α Klotho levels were higher in patients with LVH (Z = 2.17; P = 0.03) or atrial fibrillation (Z = 2.34; P = 0.019). CONCLUSIONS: FGF-23 was higher in alcoholics than in controls, especially among cirrhotics, and soluble α Klotho levels were also higher among cirrhotics. Both were related to liver function impairment, independently of serum creatinine levels, and also showed significant associations with vascular risk factors, such as hypertension, diabetes or trunk fat amount in the case of FGF-23, or LVH or atrial fibrillation in the case of α Klotho. SHORT SUMMARY: We report increased values of fibroblast growth factor 23 (FGF-23) and soluble α Klotho in cirrhotic alcoholics. Both molecules are associated with liver function impairment, and with some cardiovascular risk factors such as diabetes, hypertension, increased body fat, left ventricular hypertrophy and atrial fibrillation independently of serum creatinine.

Transplantation of adipose-derived stem cells combined with neuregulin-microparticles promotes efficient cardiac repair in a rat myocardial infarction model.

Tissue engineering is a promising strategy to promote heart regeneration after a myocardial infarction (MI). In this study, we investigated the reparative potential of a system that combines adipose-derived stem cells (ADSCs) with microparticles (MPs) loaded with neuregulin (NRG), named ADSC-NRG-MPs, on a rat MI model. First, cells were attached to the surface of MPs encapsulating NRG and coated with a 1:1 mixture of collagen and poly-d-lysine. One week after in vivo administration, the system favored the shift of macrophage expression from a pro-inflammatory to a regenerative phenotype. At long-term, the adhesion of ADSCs to MPs resulted in an increased cell engraftment, with cells being detectable in the tissue up to three months. In consonance, better tissue repair was observed in the animals treated with cells attached to MPs, which presented thicker left ventricles than the animals treated with ADSCs alone. Moreover, the presence of NRG in the system promoted a more complete regeneration, reducing the infarct size and stimulating cardiomyocyte proliferation. Regarding vasculogenesis, the presence of ADSCs and NRG-MPs alone stimulated vessel formation when compared to the control group, but the combination of both induced the largest vasculogenic effect, promoting the formation of both arterioles and capillaries. Importantly, only when ADSCs were administered adhered to MPs, they were incorporated into newly formed vessels. Collectively, these findings demonstrate that the combination of ADSCs, MPs and NRG favored a synergy for inducing a greater and more complete improvement in heart regeneration and provided strong evidence to move forward with preclinical studies with this strategy.

Malondialdehyde as a Prognostic Factor in Alcoholic Hepatitis.

AIMS: Alcoholic hepatitis is a severe complication of alcoholism, associated with high short-term mortality. Although pathogenesis remains obscure, it is generally accepted that lipopolysaccharide-induced cytokine secretion with further generation of reactive oxygen species (ROS) play outstanding roles. Prognosis is uncertain, and the usually employed prognostic scores do not include variables related to ROS generation. Therefore, this study was performed to assess short-term prognostic value of cytokines, nutritional status, different scores [Maddrey, model for end-stage liver disease (MELD), albumin, bilirubin, INR, creatinine index (ABIC), Lille, Glasgow, MELD-Na, Child-Pugh] and malondialdehyde (MDA, as an indicator of lipid peroxidation) at admission and after 1 week, among patients affected by severe acute alcoholic hepatitis (Maddrey index >32). METHODS: Sixty-two patients affected by severe acute alcoholic hepatitis, for whom we calculated Maddrey, MELD, ABIC, Lille, Glasgow, MELD-Na, Child-Pugh, and determined serum MDA and interleukin (IL)-6, IL-8, IL-4, tumor necrosis factor alpha and interferon gamma levels at admission and after 1 week. RESULTS: Twenty-four patients died during the follow-up period. MDA showed a better prognostic accuracy than the aforementioned scores, both at admission and after 1 week. CONCLUSION: Our study supports the importance of including MDA assessment in the prognostic evaluation of patients with alcoholic hepatitis. SHORT SUMMARY: Alcoholic hepatitis is associated with high short-term mortality. Although not included in prognostic scores, lipid peroxidation plays an outstanding role in its pathogenesis. We found that malondialdehyde levels showed a better prognostic accuracy than the usually employed scores. Therefore, it should be included in the prognostic evaluation of these patients.

Brain delivery of microencapsulated GDNF induces functional and structural recovery in parkinsonian monkeys.

Glial cell line-derived neurotrophic factor (GDNF) remains the most potent neurotrophic factor for dopamine neurons. Despite its potential as treatment for Parkinson's disease (PD), its clinical application has been hampered by safety and efficacy concerns associated with GDNF's short in vivo half-life and with significant brain delivery obstacles. Drug formulation systems such as microparticles (MPs) may overcome these issues providing protein protection from degradation and sustained drug release over time. We therefore sought to evaluate the efficacy and safety of GDNF delivered via injectable biodegradable MPs in a clinically relevant model of PD and to investigate the mechanism contributing to their beneficial effects. MPs were injected unilaterally into the putamen of parkinsonian monkeys with severe nigrostriatal degeneration. Notably, a single administration of the microencapsulated neurotrophic factor achieved sustained GDNF levels in the brain, providing motor improvement and dopaminergic function restoration. This was reflected by a bilateral increase in the density of striatal dopaminergic neurons 9 months after treatment. Moreover, GDNF was retrogradely transported to the substantia nigra increasing bilaterally the number of dopaminergic and total neurons, regardless of the severe degeneration. GDNF-MP injection within the putamen elicited no adverse effects such as immunogenicity, cerebellar degeneration or weight loss. MPs are therefore a safe, efficient vehicle for sustained protein delivery to the brain, supporting the therapeutic benefit of GDNF when encapsulated within MPs for brain repair. Overall, these findings constitute important groundwork for GDNF-MP clinical development.

Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

AIMS: Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. METHODS: We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. RESULTS: A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. CONCLUSION: Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. SHORT SUMMARY: Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis. We studied 59 patients and found that liver function derangement, vitamin B12 and homocysteine levels are all independently related to brain atrophy assessed by computed tomography, although we found no association between these parameters and cognitive alterations.

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion.

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

Biocompatible polymer-metal-organic framework composite patches for cutaneous administration of cosmetic molecules.

Despite increasing interest in metal-organic frameworks (MOFs) in the biomedical field, developing specific formulations suitable for different administration routes is still a main challenge. Here, we propose a simple, fast and bio-friendly press-molding method for the preparation of cutaneous patches based on composites made from the drug nanocarrier MIL-100(Fe) and biopolymers. The physicochemical properties of the patches (structure, hydration, bioadhesive and swelling properties), as well as their encapsulation and release capabilities (both in ex vitro and ex vivo models), were evaluated using active ingredients such as the challenging cosmetic liporeductor, caffeine, and the model analgesic and anti-inflammatory drug, ibuprofen. In particular, very high caffeine loadings were entrapped within these cutaneous devices with progressive releases under simulated cutaneous physiological conditions as a consequence of the swelling of the hydrophilic patches. Despite the absence of any cutaneous bioadhesive character, these patches provided progressive and suitable permeation of their cosmetic cargo through the skin, interestingly reaching the targeted adipose tissue. This makes these cosmetic-containing composite MOF-based patches promising candidates for new cutaneous devices in cosmetic applications.

Neumotórax espontáneo y parto: a propósito de un caso / Spontaneous pneumothorax and delivery: a case report

La aparición de un neumotórax espontáneo durante la gestación es infrecuente. Sin embargo, debido a los cambios fisiológicos del sistema respiratorio durante el embarazo, cualquier entidad que provoque una alteración en la ventilación afecta gravemente tanto a la gestante como al feto, por lo que ante una gestante que presente disnea y dolor torácico debería excluirse el diagnóstico de neumotórax. Se expone el caso de una mujer multípara con 39 semanas de amenorrea que presentó un neumotórax espontáneo; tras su ingreso en la UCI y la colocación de tubo pleural con válvula de Heimlich, se inicia trabajo de parto, con nacimiento de un niño sano tras parto instrumentado con analgesia epidural. Posparto de evolución normal; a los dos días se retira el tubo torácico y se remite para tratamiento quirúrgico definitivo

The onset of spontaneous pneumothorax during pregnancy is uncommon. However, due to the physiological changes of the respiratory system during pregnancy, any entity that causes an alteration in the ventilation, seriously affects both the pregnant woman and fetus. Pneumothorax should be excluded when presented with a pregnant woman with dyspnea and chest pain. We report the case of a multiparous woman with 39 weeks of amenorrhea who presented spontaneous pneumothorax. After admission to the ICU and placement of a pleural tube with a Heimlich valve, labour began. Epidural analgesia was used, and a healthy child was born after instrumental delivery. Postpartum had a normal evolution; Two days later, the Thoracic tube was removed and the mother referred for definitive surgical treatment

Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity.

Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms. With the aim of overcoming these drawbacks, lipid nanoparticles (LN) have been proposed as an alternative, since excipients are biocompatible and also a large amount of surfactants and organic solvents can be avoided. CsA was successfully incorporated into LN using the method of hot homogenization followed by ultrasonication. Three different formulations were optimized for CsA oral administration, using different surfactants: Tween(®) 80, phosphatidylcholine, taurocholate and Pluronic(®) F127 (either alone or mixtures). Freshly prepared Precirol nanoparticles showed mean sizes with a narrow size distribution ranging from 121 to 202 nm, and after freeze-drying were between 163 and 270 nm, depending on the stabilizer used. Surface charge was negative in all LN developed. High CsA entrapment efficiency of approximately 100% was achieved. Transmission electron microscopy was used to study the morphology of the optimized LN. Also, the crystallinity of the nanoparticles was studied by X-ray powder diffraction and differential scanning calorimetry. The presence of the drug in LN surfaces was confirmed by X-ray photoelectron spectroscopy. The CsA LN developed preserved their physicochemical properties for 3 months when stored at 4°C. Moreover, when the stabilizer system was composed of two surfactants, the LN formulations were also stable at room temperature. Finally, the new CsA formulations showed in vitro dose-dependent immuno-suppressive effects caused by the inhibition of IL-2 levels secreted from stimulated Jurkat cells. The findings obtained in this paper suggest that new lipid nanosystems are a good alternative to produce physicochemically stable CsA formulations for oral administration.

Glucose homeostasis changes and pancreatic ß-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus.

BACKGROUND: Switching to cyclosporine A may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown. METHODS: Obese Zucker rats were used as a model for tacrolimus-induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus for 11 days (0.3mg/kg/day) until diabetes development; then: (a)22 rats were euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and (b)22 rats on tacrolimus were shifted to cyclosporin (2.5mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and were used as a control group. All animals underwent an intraperitoneal glucose tolerance test at the end of the study. RESULTS: ß-cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed a significant improvement in blood glucose levels in all assessment points in intraperitoneal glucose tolerance test. Diabetes decreased from 100% in tacrolimus-day 12 group to 50% in tacrolimus-cyclosporin group. Compared to tacrolimus-day 12 group, rats in tacrolimus-cyclosporin group showed an increased ß-cell proliferation, but such an increase was lower than in rats receiving the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and rats receiving the vehicle were comparable. CONCLUSION: An early switch from tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an increased ß-cell proliferation and reversion of diabetes in 50% of cases.

[Prognostic value of serum homocysteine levels in elderly hospitalized patients]. / VALOR PRONÓSTICO DE LA HOMOCISTEÍNA SÉRICA EN ENFERMOS ANCIANOS HOSPITALIZADOS EN UN SERVICIO DE MEDICINA INTERNA.

BACKGROUND AND OBJECTIVES: Increased serum homocysteine levels are related to vascular disease and increased mortality. The decrease of homocysteine is also associated with a worse prognosis in patients on hemodialysis; however, this relationship has not been well studied in other patients. Our goal is to study the prognosis of increased and decreased serum homocysteine levels in elderly patients admitted to a general internal medicine unit. PATIENTS AND METHODS: We included 239 patients (121 women and 118 men; mean age, 78 years) in which we determined serum homocysteine levels and study its relationship with vascular risk factors, vascular disease: ischemic heart disease, ischemic stroke and peripheral arterial disease, nutritional status, creatinine, albumin, folate and B12 vitamin. RESULTS: Mortality during hospitalization of patients with homocysteine levels below 9 µmol/l was 33%, 9% for those with levels between 9 and 20 µmol/l and 17% for those with levels above 20 µmol/l. Low homocysteine values were related to increased comorbidity, higher degree of weight loss and decreased serum albumin levels. In a survival analysis using Kaplan-Meier curves, increased homocysteine was associated with increased mortality especially in patients with vascular disease. CONCLUSION: In elderly patients with multiple comorbidities, both decreased and increased serum homocysteine levels are associated with increased mortality.

Antecedentes y objetivos: el aumento de la homocisteína se relaciona con la enfermedad vascular y un incremento de la mortalidad. La disminución de la homocisteína se asocia también con un peor pronóstico en enfermos en hemodiálisis; sin embargo, esta relación no ha sido bien estudiada en otro tipo de pacientes. El objetivo del estudio fue analizar el valor pronóstico de los niveles de homocisteína en enfermos ancianos pluripatológicos ingresados en un servicio general de medicina interna Pacientes y métodos: estudiamos a 239 pacientes (121 mujeres y 118 varones; edad media: 78 años) en los que determinamos la homocisteína sérica y la relacionamos con los factores de riesgo vascular, enfermedad vascular: cardiopatía isquémica, ACV isquémico y arteriopatía periférica, estado de nutrición, creatinina, albúmina, ácido fólico y vitamina B12. Resultados: la mortalidad durante el ingreso de los enfermos con homocisteína menor de 9 mol/l fue del 33%, del 9% cuando estaba entre 9 y 20 mol/l y del 17% si era superior a 20 mol/l. La disminución de la homocisteína se relacionó con mayor comorbilidad, pérdida de peso y disminución de la albúmina. A largo plazo, el aumento de la homocisteína se relacionó con mayor mortalidad, especialmente en los pacientes con enfermedad vascular. Conclusión: en los pacientes ancianos pluripatológicos tanto la disminución como el aumento de la homocisteína se asocian con una mayor mortalidad.

Cambios en la homeostasis de la glucosa y la proliferación de la célula beta pancreática tras el cambio a ciclosporina en la diabetes inducida por tacrolimus / Glucose homeostasis changes and pancreatic beta-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus

Antecedentes: El cambio a ciclosporinaA podría revertir la diabetes inducida por tacrolimus. Sin embargo, los mecanismos de esta reversibilidad se desconocen. Métodos: Usamos como modelo de diabetes inducida por tacrolimus las ratas Zucker obesas. Un grupo de 44 ratas Zucker obesas fue tratado con tacrolimus durante 11 días (0,3mg/kg/día) hasta que desarrollaron diabetes; posteriormente, a)22 fueron sacrificadas a día 12 como grupo referencia (tacrolimus-d12), y b)en otras 22 el tacrolimus fue reemplazado por ciclosporina (2,5mg/kg/día) durante 5 días (tacrolimus-ciclosporina). Veintidós ratas Zucker obesas recibieron vehículo durante 17 días (grupo control). A todos los animales se les realizó una sobrecarga intraperitoneal de glucosa al final del experimento. Resultados: Se analizó la proliferación de la célulaβ, la apoptosis y la expresión del gen Ins2. En el grupo tacrolimus-ciclosporina, los niveles de glucemia mejoraron significativamente en cada punto del test intraperitoneal de glucosa comparados con el grupo tacrolimus-d12. La diabetes se redujo del 100% en los tacrolimus-d12 hasta el 50% en tacrolimus-ciclosporina. La proliferación de las células β en tacrolimus-ciclosporina se incrementó en comparación con tacrolimus-d12, pero fue menor que en los tratados con vehículo. La expresión génica de Ins2en tacrolimus-ciclosporina fue comparable a los tratados con el vehículo. Conclusión: El cambio temprano de tacrolimus por ciclosporina en la diabetes inducida por tacrolimus incrementa la proliferación de la célulaβ y revierte la diabetes en un 50% de los casos (AU)

Background: Switching to cyclosporinA may result in a reversion of tacrolimus-induced diabetes mellitus. However, mechanisms underlying such a reversion are still unknown. Methods: Obese Zucker rats were used as a model for tacrolimus-induced diabetes mellitus. A cohort of 44 obese Zucker rats received tacrolimus for 11 days (0.3mg/kg/day) until diabetes development; then: (a)22 rats were euthanized at day 12 and were used as a reference group (tacrolimus-day 12), and (b)22 rats on tacrolimus were shifted to cyclosporin (2.5mg/kg/day) for 5 days (tacrolimus-cyclosporin). An additional cohort of 22 obese Zucker rats received the vehicle for 17 days and were used as a control group. All animals underwent an intraperitoneal glucose tolerance test at the end of the study. Results: β-cell proliferation, apoptosis and Ins2 gene expression were evaluated. Compared to rats in tacrolimus-day 12 group, those in tacrolimus-cyclosporin group showed a significant improvement in blood glucose levels in all assessment points in intraperitoneal glucose tolerance test. Diabetes decreased from 100% in tacrolimus-day 12 group to 50% in tacrolimus-cyclosporin group. Compared to tacrolimus-day 12 group, rats in tacrolimus-cyclosporin group showed an increased β-cell proliferation, but such an increase was lower than in rats receiving the vehicle. Ins2 gene expressions in rats receiving tacrolimus-cyclosporin and rats receiving the vehicle were comparable. Conclusion: An early switch from tacrolimus to cyclosporin in tacrolimus-induced diabetes mellitus resulted in an increased β-cell proliferation and reversion of diabetes in 50% of cases (AU)

Valor pronóstico de la homocisteína sérica en enfermos ancianos hospitalizados en un servicio de medicina interna / Prognostic value of serum homocysteine levels in elderly hospitalized patients

Antecedentes y objetivos: el aumento de la homocisteína se relaciona con la enfermedad vascular y un incremento de la mortalidad. La disminución de la homocisteína se asocia también con un peor pronóstico en enfermos en hemodiálisis; sin embargo, esta relación no ha sido bien estudiada en otro tipo de pacientes. El objetivo del estudio fue analizar el valor pronóstico de los niveles de homocisteína en enfermos ancianos pluripatológicos ingresados en un servicio general de medicina interna Pacientes y métodos: estudiamos a 239 pacientes (121 mujeres y 118 varones; edad media: 78 años) en los que determinamos la homocisteína sérica y la relacionamos con los factores de riesgo vascular, enfermedad vascular: cardiopatía isquémica, ACV isquémico y arteriopatía periférica, estado de nutrición, creatinina, albúmina, ácido fólico y vitamina B12. Resultados: la mortalidad durante el ingreso de los enfermos con homocisteína menor de 9 μmol/l fue del 33%, del 9% cuando estaba entre 9 y 20 μmol/l y del 17% si era superior a 20 μmol/l. La disminución de la homocisteína se relacionó con mayor comorbilidad, pérdida de peso y disminución de la albúmina. A largo plazo, el aumento de la homocisteína se relacionó con mayor mortalidad, especialmente en los pacientes con enfermedad vascular. Conclusión: en los pacientes ancianos pluripatológicos tanto la disminución como el aumento de la homocisteína se asocian con una mayor mortalidad (AU)

Background and objectives: increased serum homocysteine levels are related to vascular disease and increased mortality. The decrease of homocysteine is also associated with a worse prognosis in patients on hemodialysis; however, this relationship has not been well studied in other patients. Our goal is to study the prognosis of increased and decreased serum homocysteine levels in elderly patients admitted to a general internal medicine unit. Patients and methods: we included 239 patients (121 women and 118 men; mean age, 78 years) in which we determined serum homocysteine levels and study its relationship with vascular risk factors, vascular disease: ischemic heart disease, ischemic stroke and peripheral arterial disease, nutritional status, creatinine, albumin, folate and B12 vitamin. Results: mortality during hospitalization of patients with homocysteine levels below 9 µmol/l was 33%, 9% for those with levels between 9 and 20 µmol/l and 17% for those with levels above 20 µmol/l. Low homocysteine values were related to increased comorbidity, higher degree of weight loss and decreased serum albumin levels. In a survival analysis using Kaplan-Meier curves, increased homocysteine was associated with increased mortality especially in patients with vascular disease. Conclusion: in elderly patients with multiple comorbidities, both decreased and increased serum homocysteine levels are associated with increased mortality (AU)

Esclerostina y grasa corporal / Sclerostin and body fat

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