Coronary heart disease mortality is decreasing in Argentina, and Colombia, but keeps increasing in Mexico: a time trend study.

BACKGROUND: Mortality rates due to coronary heart disease (CHD) have decreased in most countries, but increased in low and middle-income countries. Few studies have analyzed the trends of coronary heart disease mortality in Latin America, specifically the trends in young-adults and the effect of correcting these comparisons for nonspecific causes of death (garbage codes). The objective of this study was to describe and compare standardized, age-specific, and garbage-code corrected mortality trends for coronary heart disease from 1985 to 2015 in Argentina, Colombia, and Mexico. METHODS: Deaths from coronary heart disease were grouped by country, year of registration, sex, and 10-year age bands to calculate age-adjusted and age and sex-specific rates for adults aged ≥25. We corrected for garbage-codes using the methodology proposed by the Global Burden of Disease. Finally, we fitted Joinpoint regression models. RESULTS: In 1985, age-standardized mortality rates per 100,000 population were 136.6 in Argentina, 160.6 in Colombia, and 87.51 in Mexico; by 2015 rates decreased 51% in Argentina and 6.5% in Colombia, yet increased by 61% in Mexico, where an upward trend in mortality was observed in young adults. Garbage-code corrections produced increases in mortality rates, particularly in Argentina with approximately 80 additional deaths per 100,000, 14 in Colombia and 13 in Mexico. CONCLUSIONS: Latin American countries are at different stages of the cardiovascular disease epidemic. Garbage code correction produce large changes in the mortality rates in Argentina, yet smaller in Mexico and Colombia, suggesting garbage code corrections may be needed for specific countries. While coronary heart disease (CHD) mortality is falling in Argentina, modest falls in Colombia and substantial increases in Mexico highlight the need for the region to propose and implement population-wide prevention policies.

[Biometric analysis of the Spanish studies on neurorehabilitation in cases of stroke indexed in Medline (2008-2017)]. / Analisis bibliometrico de las investigaciones españolas sobre neurorrehabilitacion en el ictus indizadas en Medline (2008-2017).

TITLE: Analisis bibliometrico de las investigaciones españolas sobre neurorrehabilitacion en el ictus indizadas en Medline (2008-2017).

Results of a multi-faceted educational intervention to prevent peripheral venous catheter-associated bloodstream infections.

Peripheral venous catheter-associated bloodstream infections (PVC-BSIs) lead to prolonged hospitalization, morbidity and increased costs. The impact of infection-prevention measures on the rate of PVC-BSIs in a university hospital in Spain was assessed. An active surveillance programme was initiated in 2015, which revealed a high PVC-BSI incidence ratio (0.48/1000 patient-days). A bundle aimed at nurses, medical staff and patients was implemented, and a Catheter Infection Team (CIT) was set up. The intervention achieved a decrease in PVC-BSI rate: 0.34 in 2016, 0.29 in 2017, and 0.17 in 2018. The decline was greatest for Gram-negative PVC-BSIs (67.6% in 2015, 35.3% in 2018).

Experimental models in traumatic brain injury: from animal models to in vitro assays. / Principales modelos experimentales de traumatismo craneoencefálico: de la preclínica a los modelos in vitro.

Traumatic brain Injury (TBI) is a major public healthcare concern, affecting people of all ages. Despite advances in the diagnosis, monitoring and clinical management of TBI, many unresolved questions remain regarding its physiopathology. In an attempt to understand the pathological features of TBI and to evaluate single potential therapeutic strategies, various animal models have been developed to simulate the mechanisms of action and the clinical manifestations of TBI patients. In turn, each model represents a specific type of trauma and evaluates a specific physiopathological aspect of the cascade triggered as a result of TBI. This review describes the main experimental models currently available referred to TBI and their possible application to the clinical setting.

Estado nutricional, factores sociodemográficos y de salud en estudiantes de nuevo ingreso a la UAZ / Nutritional status and social-demographical and health factors among newly enrolled students at UAZ / Estado nutricional, fatores sociodemográficos e de saúde em estudantes de novo ingresso à UAZ

Introducción El sobrepeso y obesidad son factores de riesgo para desarrollar complicaciones a corto y largo plazo. La población de nuevo ingreso a la universidad se considera un colectivo, especialmente, vulnerable desde el punto de vista nutricional. Objetivo Describir el estado nutricional, factores sociodemográficos y de salud en estudiantes de nuevo ingreso a la UAZ. Metodología Estudio de tipo observacional, transversal y descriptivo, que se realizó a 3,972 estudiantes universitarios de nuevo ingreso. Se logró el consentimiento verbal de los alumnos. Se capacitaron y estandarizaron a los pasantes de enfermería, medicina y nutrición, para llevar a cabo las mediciones. Se obtuvo información del estado nutricional, factores sociodemográficos y salud, así como mediciones antropométricas. Resultados Los hombres tienen mayor prevalencia de sobrepeso (24.1%) y obesidad (9.2%) que las mujeres (p < 0.001). Los hombres realizan mayor actividad física (73.6% vs 51.1%), consumen más alcohol (58.3% vs 34.3%) y tabaco (20.8% vs 9.5%) (p < 0.000). Se encontró una asociación positiva en los momios de sobrepeso en relación con los hombres (RM=1.22, IC 95% 1.02-1.45), edad de 19 años (RM=1.36, IC 95% 1.02-1.45), en las áreas de ciencias de la salud (RM=1.88, IC 95% 1.05-3.35), ciencias sociales (RM=1.93, IC 95% 1.06-3.48), humanidades y educativas (RM=1.90, IC 95% 1.01-3.53), ingenierías y tecnologías (RM=1.83, IC 95% 1.01-3.30). Discusión y conclusión Se puede contribuir a reducir las prevalencias de sobrepeso y obesidad de los estudiantes, a través de intervenciones dirigidas a modificar las conductas de riesgo durante la estancia universitaria, mejorar la alimentación y promover estilos de vida saludables.

Introduction Obesity and overweight are risk factors to developing short and long-term health-related complications; and newly enrolled university students are considered a vulnerable group in terms of their nutritional progression status. Objective To describe the nutritional status, and social-demographical and health factors among newly enrolled students at UAZ. Methodology This is an observational, transversal, and descriptive study on a sample of 3,972 newly enrolled university students who verbally consented on their participation. Nursing, medicine, and nutrition intern students were trained to carry out diverse assessments related to the nutritional status, social-demographical and health factors, and anthropometric data on the sample. Results Newly enrolled male students showed a higher prevalence of overweight (24.1%) and obesity (9.2%) in comparison to their female counterparts (p < .001). Male students showed having more physical activity (73.6% vs 51.1%) but also consuming more alcohol (58.3% vs 34.3%) and tobacco (20.8% vs 9.5%) (p < .000). Positive associations were found between the overweight numbers and, being male (RM=1.22, CI 95% 1.02-1.45), being 19 years old (RM = 1.36, CI 95% 1.02-1.45), being in the areas of health sciences (RM=1.88, CI 95% 1.05-3.35), being in the areas of social sciences (RM=1.93, CI 95% 1.06-3.48), being in the areas of humanities and education (RM=1.90, CI 95% 1.01-3.53), and being in the areas of engineering and technology (RM=1.83, CI 95% 1.01-3.30). Discussion and conclusion It is necessary to address to obesity and overweight problems among university students through interventions aimed at modifying risky behaviors during their university stay, improving the quality of nutrition, and promoting healthy life-styles.

Introdução O sobrepeso e a obesidade são fatores de risco para desenvolver complicações a curto e longo prazo. A população de novo ingresso à universidade considera-se um coletivo, especialmente, vulnerável desde o ponto de vista nutricional. Objetivo Descrever o estado nutricional, fatores sociodemográficos e de saúde em estudantes de novo ingresso à UAZ. Metodologia Estudo de tipo observacional, transversal e descritivo, que se realizou a 3,972 estudantes universitários de novo ingresso. Conseguiu-se o consentimento verbal dos alunos. Capacitaram-se e padronizaram os formados de enfermagem, medicina e nutrição, para levar a cabo as medições. Obteve-se informação do estado nutricional, fatores sociodemográficos e saúde, assim como medições antropométricas. Resultados Os homens de novo ingresso têm maior prevalência de sobrepeso (24.1%) e obesidade (9.2%) quanto as mulheres (p < 0.001). Homens realizam mais atividade física que mulheres (73.6% vs. 51.1%), consomem mais álcool (58.3% vs. 34.3%) e tabaco (20.8% vs. 9.5%) (p < 0.000). Encontrou-se uma associação positiva nas chances de sobrepeso em relação com aos homens (RM = 1.22, IC 95% 1.02-1.45), ter 19 anos de idade (RM = 1.36, IC 95% 1.02-1.45) nas áreas de ciências da saúde (RM = 1.88, IC 95% 1.05-3.35), ciências sociais (RM = 1.93, IC 95% 1.06-3.48), humanidades e educativas (RM = 1.90, IC 95% 1.01-3.53), engenharias e tecnologias (RM = 1.83, IC 95% 1.01-3.30). Discussão e conclusão Pode-se contribuir a reduzir as prevalências de sobrepeso e obesidade dos estudantes, a través de intervenções dirigidas a modificar as condutas de risco durante a permanência universitária, melhorar a alimentação e promover estilos de vida saudáveis.

[APACHE II and SAPS II as predictors of brain death development in neurocritical care patients]. / APACHE II y SAPS II como predictores de evolucion a muerte encefalica en pacientes neurocriticos.

AIM: To assess the prognostic value of APACHE II and SAPS II scales to predict brain death evolution of neurocritical care patients. PATIENTS AND METHODS: Retrospective observational study performed in a tertiary hospital. Include 508 patients over 16 years old, hospitalized in ICU for at least 24 hours. The variables of interest were: demographic data, risk factors, APACHE II, SAPS II and outcome. RESULTS: Median age: 41 years old (IR: 25-57). Males: 76.2%. Most frequent reason for admission: trauma (55.3%). Medians: Glasgow Coma Scale (GCS), 10 points; APACHE II, 13 points; SAPS II, 31 points; and ICU stay, 5 days. Mortality in the ICU was 28.5% (n = 145) of whom 44 (8.7%) evolved to brain death. Univariate logistic regression analysis showed that GCS, APACHE II and SAPS II scores, as well as ICU stay days behaved as predictors of brain death evolution. However, the multivariate analysis performed including APACHE II and SAPS II scores showed that only APACHE II maintained statistical significance, despite the good discrimination of both scores. CONCLUSION: Transplant coordinators might use the APACHE II score as a tool to detect patients at risk of progression to brain death, minimizing the loss of potential donors.

TITLE: APACHE II y SAPS II como predictores de evolucion a muerte encefalica en pacientes neurocriticos.Objetivo. Evaluar si las escalas pronosticas APACHE II (Acute Physiology and Chronic Health Evaluation II) y SAPS II (Simplified Acute Physiology Score II) son capaces de predecir la evolucion a muerte encefalica en pacientes neurocriticos. Pacientes y metodos. Estudio retrospectivo, observacional, realizado en un hospital de tercer nivel. Se incluyo a 508 pacientes mayores de 16 años, ingresados con patologia neurocritica aguda, con estancia en la unidad de cuidados intensivos de al menos 24 horas. Las variables de interes fueron: datos demograficos, factores de riesgo, APACHE II, SAPS II y resultado pronostico. Resultados. Mediana de edad: 41 años (rango intercuartilico: 25-57). Varones: 76,2%. Motivo de ingreso mas frecuente: traumatismo (55,3%). Medianas: escala de coma de Glasgow (GCS), 10 puntos; APACHE II, 13 puntos; SAPS II, 31 puntos; y estancia en cuidados intensivos, cinco dias. La mortalidad en la unidad de cuidados intensivos fue de 145 (28,5%). De ellos, 44 (8,7%) evolucionaron a muerte encefalica. El analisis de regresion logistica univariante mostro que la GCS, las escalas APACHE II y SAPS II, y los dias de estancia en la unidad de cuidados intensivos se comportaron como variables predictoras de evolucion a muerte encefalica. Sin embargo, en el analisis multivariante realizado con APACHE II y SAPS II, se evidencio que solo APACHE II mantiene significacion estadistica, a pesar de la buena discriminacion de ambas escalas. Conclusion. Los coordinadores de trasplantes podrian usar la escala APACHE II como una herramienta para detectar pacientes con riesgo de evolucion a muerte encefalica, minimizando la perdida de potenciales donantes.

Orthotopic Liver Transplantation: Preliminary Analysis of Complications With Grafts From Elderly Donors.

OBJECTIVE: This study aims to determine if donor grafts of patients older than 65 years develop more post-transplantation complications than those of younger patients. DESIGN: This is a retrospective, observational study of liver transplant recipients during 12 months in Virgen del Rocio University Hospital. We compare incidence rates of reperfusion syndrome, acute kidney injury, and need for intra- and postoperative red blood cell transfusions in two donor age groups in which group A is <65 years old and group B is ≥65 years old. RESULTS: Sixty cases were included. Reperfusion syndrome, acute kidney injury, and both intra- and postoperative red blood cell transfusion were more frequent in group A than group B (11.4% vs. 4%, P = .390; 44% vs. 32%, P = .423; 68.8% vs. 48%, P = .120; and 70.6% vs. 64%, P = .779, respectively). Six recipients (17.1%) died at 12 months from group A whereas there were no deaths register in group B during that time (P = .036). CONCLUSION: Our results showed that including elderly donors does not aggravate incidence of complications, emphasizing that advanced age should not be an exclusion criteria for liver transplantation.

Deciphering Tacrolimus-Induced Toxicity in Pancreatic ß Cells.

ß Cell transcription factors such as forkhead box protein O1 (FoxO1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), pancreatic and duodenal homeobox 1, and neuronal differentiation 1, are dysfunctional in type 2 diabetes mellitus (T2DM). Posttransplant diabetes mellitus resembles T2DM and reflects interaction between pretransplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors (CNIs). We evaluated the effect of tacrolimus (TAC), cyclosporine A (CsA), and metabolic stressors (glucose plus palmitate) on insulinoma ß cells in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for 5 days with 100 µM palmitate and 22 mM glucose; CsA (250 ng/mL) or TAC (15 ng/mL) were added in the last 48 h. Glucose plus palmitate increased nuclear FoxO1 and decreased nuclear MafA. TAC in addition to glucose plus palmitate magnified these changes in nuclear factors, whereas CsA did not. In addition to glucose plus palmitate, both drugs reduced insulin content, and TAC also affected insulin secretion. TAC withdrawal or conversion to CsA restored these changes. Similar results were observed in pancreata of obese animals on CNIs. TAC and CsA, in addition to glucose plus palmitate, induced comparable inhibition of calcineurin and nuclear factor of activated T cells (NFAT); therefore, TAC potentiates glucolipotoxicity in ß cells, possibly by sharing common pathways of ß cell dysfunction. TAC-induced ß cell dysfunction is potentially reversible. Inhibition of the calcineurin-NFAT pathway may contribute to the diabetogenic effect of CNIs but does not explain the stronger effect of TAC compared with CsA.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

[Usefulness of biomarkers in the prognosis of severe head injuries]. / Utilidad de los biomarcadores en el pronóstico del traumatismo craneoencefálico grave.

Severe head injuries have a great socioeconomic and public health impact. Despite progress in diagnosis and treatment, no sufficiently reliable predictive models have been established for developing clinical trials and promoting effective therapeutic strategies capable of improving the prognosis. In the last decades, several brain damage biomarkers have been studied as potential diagnostic and prognostic tools in traumatic brain injury. However, all of them have limitations that preclude their universalized application. The properties of the known biomarkers -both those traditionally shown to correlate with severity and prognosis, and those recently announced as promising options- should be analyzed. New studies are needed to define their properties, both isolatedly and in combined use.

Brain injury biomarkers in the setting of cardiac surgery: Still a world to explore.

BACKGROUND: Brain injury is an important, potentially devastating, complication in cardiac surgery. A significant number of patients suffer perioperative complications involving the central nervous system. Clinical manifestations of brain injury are associated with significantly increased mortality, morbidity and health resource utilization. Serum biomarkers have been studied in cardiac surgery to measure the degree and incidence of brain injury and to improve patient management. METHODS: All relevant studies were identified by computerized searches of PubMed using the following Medical Subject Headings and keywords term: biomarker, cardiac surgery, brain injury and neurological complication. RESULTS: The biomarkers that appear to be better indicators of brain injury severity in cardiac surgery and its consequences are S100B protein, neuron-specific enolase, glial fibrillary acidic protein, tau protein, matrix metalloproteinase-9, ubiquitin C terminal hydroxylase-L1 and neurofilaments. CONCLUSIONS: These biomarkers, independently of clinical and radiological findings, show global cerebral situation at the cellular level and the degree of brain dysfunction. However, up to date, there is no biomarker entirely suitable for the detection of brain injury after cardiac surgery.

Entheseal changes and sexual division of labor in a North-African population: The case of the pre-Hispanic period of the Gran Canaria Island (11th-15th c. CE).

The aim of this paper is to investigate the relationship between entheseal changes and sexual division of labor in the pre-Hispanic population of Gran Canaria Island (Spain). Ethnohistorical records from the period of contact between Europeans and the Canarian indigenous population provide rich information about the different activities performed by men and women. For this purpose, entheseal changes in a sample of 138 individuals (82 males and 56 females) buried in ten pre-Hispanic cemeteries (11th and 15th centuries cal. CE) were analyzed. Forty-one entheses located in the clavicle, humerus, ulna and radius were analyzed (fibrous and fibro-cartilaginous attachment sites). Entheses were graded using a visual and descriptive standard which summarized the entheseal changes. This method interprets the changes as a sign of robustness on a scale from low to high development and includes enthesopathies. The intra- and inter-observer error of this method was minimal. Sex differences in the degree of robustness, bilateral asymmetry, sexual dimorphism and principal components analyses were tested in this sample. The results indicate significant variance in the entheseal robustness between males and females. They also suggest the impact of certain biomechanical chains (pronosupination, shoulder rotation, etc.) in entheseal changes. These results contribute to an interdisciplinary approach to the study of the sexual division of labor in the pre-Hispanic society of Gran Canaria.

[An experimental model of mass-type brain damage in the rat: expression of brain damage based on neurospecific enolase and protein S100B]. / Modelo experimental de lesión cerebral tipo masa en rata: expresión del daño cerebral mediante enolasa neuroespecífica y proteína S100B.

OBJECTIVE: To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the induced brain injury. DESIGN: An experimental study with a control group. SETTING: Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: Fourteen adult Wistar rats. INTERVENTIONS: Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 µl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation. PRIMARY STUDY VARIABLES: Weight, early mortality, serum NSE and S100B concentration. RESULTS: Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker. CONCLUSIONS: Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat.

Serologic behavior of S100B protein in patients who are brain dead: preliminary results.

OBJECTIVE: The objective of this study is to assess the S100B protein serum concentrations from brain dead (BD) donors to understand whether its level could provide clinical information during BD diagnosis as a potential confirmatory test. METHODS: During 12 months, 26 patients declared BD were prospectively included in this study. Once the diagnosis of BD was achieved, serum S100B protein levels were measured using an electrochemiluminescence assay. For analytical purposes, we selected the maximum S100B serum value reached during the first 5 days of evolution from a historical cohort of 124 survived patients after a severe brain injury (SBI), as well as from 18 healthy donors (HD) and a subgroup of patients who had severe traumatic brain injuries (TBIs) without extracranial injuries. RESULTS: Mean age was 53.48 years (SD, 18.91 years). The BD group had significantly higher S100B serum levels (1.44 µg/L; interquartile ratio [IR], 0.63-3.68) than the SBI (0.34 µg/L; IR, 0.21-0.60) and HD groups (0.06 µg/L; IR, 0.03-0.07; P < .001). Analysis of S100B levels depending on the main cause responsible for BD development showed significant differences between subgroups (P = .012). S100B serum levels were higher in the isolated TBI BD group (P = .004). The S100B value showed an odds ratio for BD diagnosis of 8.38 (95% confidence interval [CI], 1.16-60.45; P = .035). Reciever operating characteristic analysis revealed an area under the curve of 0.92 (95% CI, 0.79-1.00; P = .007). We set a cut-off value of 2 µg/L in S100B serum concentrations. At this level, the diagnostic properties of S100B would reach 100% of specificity and positive predictive value (PPV), and sensitivity and negative predictive value (NPV) of 60% and 86.7%, respectively. CONCLUSION: This preliminary analysis shows for the very first time that BD is associated with higher S100B serum levels, compared with other neurocritical care patients. We also found that the cause of BD development must be considered. Specifically, S100B serum levels in severe isolated TBI patients-with clinical exploration compatible with BD-could be used in a future as confirmatory test.

The higher diabetogenic risk of tacrolimus depends on pre-existing insulin resistance. A study in obese and lean Zucker rats.

Insulin resistance may interact with calcineurin inhibitors, enhancing the diabetogenic effect of tacrolimus compared with cyclosporine-A. We studied both drugs in insulin-resistant animals: obese Zucker rats (n = 45), and insulin-sensitive animals: lean Zucker rats (n = 21). During 11 days, animals received saline-buffer, cyclosporine-A (2.5 mg/kg/day) or tacrolimus (0.3 mg/kg/day). At Days 0 and 12 animals underwent intraperitoneal glucose tolerance test (0-30-60-120 min). Islet morphometry, beta-cell proliferation, apoptosis and Ins2 gene expression were analyzed. By Day 12, no lean animal had developed diabetes, while all obese animals on tacrolimus and 40% on cyclosporine-A had. In obese animals, tacrolimus reduced beta-cell proliferation and Ins2 gene expression compared with cyclosporine-A. Five days after treatment discontinuation, partial recovery was observed, with only 10% and 60% of the animals on cyclosporine and tacrolimus remaining diabetic respectively. Beta-cell proliferation increased in animals on tacrolimus while Ins2 gene expression remained unaltered. In conclusion, insulin resistance exacerbated the diabetogenic effect of tacrolimus compared with cyclosporine-A. This may be explained by greater inhibition of Ins2 gene and beta-cell proliferation by tacrolimus in the insulin resistant state. Discontinuation of the drugs may allow the recovery of the metabolic alterations.

Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy.

BACKGROUND: The aim of this experimental study was to analyze the histomorphometric changes observed when using different doses of estradiol, calcitriol and both treatments combined, in rats with both chronic kidney disease (CKD) and ovariectomy (OVX). METHODS: Six groups of rats with CKD+OVX were treated for 8 weeks with placebo, with different doses of 17beta-estradiol (E2), with calcitriol or with both treatments combined (E2+calcitriol). Histomorphometric studies were carried out at the proximal tibia segment. RESULTS: All groups that received active treatments showed a trabecular bone volume similar to those of rats with normal ovarian function. Treatment with E2 was effective, E2-10 diminished osteoid and eroded surfaces, and E2-30 was able to achieve a bone remodeling similar to that of the normal group. Calcitriol proved to have a positive effect on bone microarchitecture, achieving normal trabecular connectivity. The combined treatment with E2-30+calcitriol was the most effective treatment as it was not only capable of achieving normal trabecular remodeling and connectivity, but also normal trabecular bone volume. CONCLUSIONS: E2 and calcitriol seem to have independent effects on cancellous bone turnover in rats with CKD+OVX. In rats with chronic kidney disease and ovariectomy, these two agents are able to produce additive effects on bone and offer additional advantages as opposed to the use of both drugs independently.