Development of a Bmi1+ Cardiac Mouse Progenitor Immortalized Model to Unravel the Relationship with Its Protective Vascular Endothelial Niche.

The adult mammalian heart has been demonstrated to be endowed with low but real turnover capacity, especially for cardiomyocytes, the key functional cell type. The source, however, of that turnover capacity remains controversial. In this regard, we have defined and characterized a resident multipotent cardiac mouse progenitor population, Bmi1+DR (for Bmi1+ Damage-Responsive cells). Bmi1+DR is one of the cell types with the lowest ROS (Reactive Oxygen Species) levels in the adult heart, being particularly characterized by their close relationship with cardiac vessels, most probably involved in the regulation of proliferation/maintenance of Bmi1+DR. This was proposed to work as their endothelial niche. Due to the scarcity of Bmi1+DR cells in the adult mouse heart, we have generated an immortalization/dis-immortalization model using Simian Vacuolating Virus 40-Large Antigen T (SV40-T) to facilitate their in vitro characterization. We have obtained a heterogeneous population of immortalized Bmi1+DR cells (Bmi1+DRIMM) that was validated attending to different criteria, also showing a comparable sensitivity to strong oxidative damage. Then, we concluded that the Bmi1-DRIMM population is an appropriate model for primary Bmi1+DR in vitro studies. The co-culture of Bmi1+DRIMM cells with endothelial cells protects them against oxidative damage, showing a moderate depletion in non-canonical autophagy and also contributing with a modest metabolic regulation.

First report of the beech leaf disease nematode Litylenchus crenatae mccannii (Nematoda: Anguinidae) in Michigan.

The North American beech leaf disease (BLD) nematode, Litylenchus crenatae mccannii Handoo, Li, Kantor, Bauchan, McCann, Gabriel, Yu, Reed, Koch, Martin and Burke, 2020, is recognized as a newly emergent nematode species that causes BLD in beech trees (Fagus spp.) in North America (Carta et al. 2020; Kantor et al. 2022a). Since the first report of BLD on American beech (Fagus grandifolia Ehrh) within the Lake County, located at the north-eastern corner of the state of Ohio in 2012 (Carta et al. 2020), the disease has rapidly spread to other US states and a province in Canada (Erwing et al. 2018; Carta et al 2020; Marra and LaMondia 2020; Reed et al 2020; Kantor et al. 2022b). Currently, besides Ohio, this nematode has been reported in Pennsylvania, New York, Connecticut, Massachusetts, Maine, Rhode Island, New Jersey, West Virginia, and Virginia, as well as Ontario, Canada. Different life stages of L. crenatae mccannii were isolated from symptomatic American beech leaves from an isolated natural maple-beech stand in rural Saint Clair Cty., Michigan, US; presenting typical symptoms of beech leaf disease, i.e., swelling and darkening of interveinal leaf tissues. Samples were taken to the Forest Pathology Laboratory at Michigan State University where L. crenatae mccannii presence was confirmed in the leaves after which samples were sent to the Mycology and Nematology Genetic Diversity and Biology Laboratory (USDA-ARS) in Beltsville, Maryland for official confirmation. Nematodes were identified based on morphology and sequence analysis of the internal transcribed spacer (ITS), and the D2D3 region of the 28S large subunit ribosomal DNA. To validate the morphological identification two different ribosomal DNA loci were amplified, sequenced and the phylogenetic relationships were generated. The amplification yielded fragments of 784 and 741 bp flanked by the ITS (GenBank accession no. OP689654) and D2D3 (GenBank accession no. OP689710) primers, respectively. The sequences obtained for the specimens collected in Michigan revealed 100% similarity to L. crenatae mccannii sequences obtained from specimens collected from other geographical areas in the US, and therefore validating the morphological analyses as well. The ITS sequence shared a 99.75% similarity with the subspecies L. crenatae (GenBank accession no. LC383724.1), and 90.53% similarity to L. coprosma Zhao, Davies, Alexander and Riley, 2011 (GU727548.1). While the D2D3 sequences of both L. crenatae subspecies revealed a 100% similarity (versus LC383725.1), they revealed 95.35% similarity to L. coprosma (KY679564.1). Since the first confirmed detection of BLD in June 2022 in St. Clair Cty, BLD has been reported in Oakland and Wayne Ctys (7 reports total across the three counties), suggesting BLD spread in the SE of Michigan. BLD confirmation was based on either physical symptoms (leaf banding), and/or the presence of the beech leaf nematode by morphological or molecular confirmation. The presence of the beech leaf nematode in symptomatic leaves follow the results obtained by Carta et al. (2020) after inoculation of beech seedlings with L. crenatae mccannii. Based on both morphological and molecular analyses the specimens collected in the state of Michigan were identified as L. crenatae mccannii. To our knowledge, this is the first report of this species in conjunction with symptomatic F. grandifolia leaves in this state.

Characterization of Diaporthe spp. Associated With Spruce Decline on Colorado Blue Spruce in Michigan.

Since 2006 there has been a decline in Colorado blue spruce (CBS; Picea pungens) planted as landscape trees and for Christmas tree production throughout the Lower Peninsula of Michigan. This decline is characterized by a slow loss of needles in the lower portion of the tree starting at branch tips, followed by entire branch dieback, which progresses upward over several years. This dieback has been linked to shallow branch cankers visible in the phloem when the bark layer is removed. Isolates in the fungal genus Diaporthe have been consistently isolated from lesion margins on symptomatic branches. Before the initial reports of declining CBS in landscape and Christmas trees, Diaporthe was known only as a nursery disease of CBS. To determine the species of Diaporthe linked to the decline of CBS in Michigan, seven gene regions were sequenced from a collection of Diaporthe isolates collected in 2011 through 2018 from CBS and other coniferous hosts. Subsequent phylogenetic analyses indicated that Diaporthe eres and a novel Diaporthe clade were present on symptomatic CBS in Michigan. The new species D. brevicancria nov. is described, and Koch's postulates were confirmed for D. brevicancria nov. and D. eres. D. brevicancria nov. produced the largest cankers in greenhouse pathogenicity trials, and dual inoculations of D. brevicancria nov. and D. eres produced intermediate cankers.

Osteoprotegerin Is the Strongest Predictor for Progression of Arterial Calcification in Peritoneal Dialysis Patients.

BACKGROUND: Arterial calcification (AC) is frequent in patients with end stage renal disease and is also considered a risk factor for later morbidity and mortality. However, long-term factors associated with the process are not well known. We analyzed the trends over time of biomarkers related with development and progression of AC in incident patients on peritoneal dialysis (PD). METHODS: We performed a prospective study with 186 patients on PD followed up for 1 year. We analyzed the progression of AC in the abdominal aorta and pelvic vessels by calcification score (CaSc), using16-cut computerized multidetector tomography at baseline and 1 year. Variables related with PD treatment, inflammation, and mineral metabolism were measured at baseline, 6, and 12 months of follow-up. Changes in biochemical variables were analyzed for their relationship with changes in AC. RESULTS: Over 1 year, the number of patients with AC increased from 47 to 56%, and CaSc from 355 (interquartile range [IQR] 75-792) to 529 (IQR 185-1632). A total of 43.5% of patients remained free of calcification, 11.7% had new calcifications, and 44.8% had progression of calcification. Older age, diabetes, high systolic blood pressure, body mass index, cholesterol, and osteoprotegerin (OPG), as well as lower levels of albumin, serum creatinine, and osteocalcin, were associated with development of new, and rapid progression of, calcification. In multivariate logistic analysis, OPG remained the most significant (OR 1.27, 95% CI 1.11-1.47, p < 0.001). CONCLUSION: OPG was the strongest risk factor associated with new development and rapid progression of AC in incident PD patients.

Public communication of science in Mexico: past, present and future of a profession.

In this article, we offer an analysis of the evolution of the professional field of public communication of science in Mexico, particularly at the National Autonomous University of Mexico, the influences it has received from other countries, the impact it has on Mexican society and some of its relationships with other Latin American countries. We present examples of successful programmes in different mass media and an analysis of the evolution and diversification of science communicators over the last four decades.

Endoscopically assisted removal of ectopic teeth in the floor of the orbit. Case report and latest literature review.

Ectopic sinonasal third molar is a rare condition characterized by the aberrant position of the third molar in the maxillar sinus. The etiology of the teeth in the maxillary sinus is commonly associated to trauma and iatrogenic dental procedures. We present the clinical case of a 33-year-old man who presents an ectopic tooth in the right maxillary sinus, located in the orbital floor, who requires endoscopic control through a maxillary approach when performing the extraction. The endoscopic technique is being increasingly used in the maxillofacial field. Thanks to the endoscopic control for complex extractions like the descibed case, complications such as injuries of the infraorbital nerve or fractures of the different walls of the sinus could be avoided. In conclusion, endoscopic control to perform tooth extractions in the maxillary sinus is a safe option that helps to avoid complications such as fracture of the maxillary sinus walls or fracture of the orbital floor. Key words:Endoscopic, ectopic tooth, caldwell luc, maxillary sinus.

Participants' Bias in Disability Research on Family Quality of Life during the 0-6 Years Stage.

BACKGROUND: Over the past two decades, various research teams have designed and applied instruments to measure the quality of life of families with a member who has a disability. A recent systematic review on the state of the Family Quality of Life in early care identified that many of these studies collected data only from the mothers. The present study aimed to investigate whether there is a bias in participant selection in these types of studies. METHOD: A systematic review of the scientific literature was conducted in three databases-Scopus, Web of Science, Eric-from 2000 to 2022. A total of 72 empirical studies were identified. RESULTS: The findings indicate that most studies examining the Family Quality of Life were based on the information of a single informant per family unit. The profiles of participants according to the research objective are quite similar. In one-third of studies, the authors reported that family members who participate cannot be represented by only mothers or one participant per household. CONCLUSIONS: Given the dynamic and collective nature of the construct, the application of a systemic approach is necessary.

Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress.

Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miRSEL). Proteomics demonstrated a highly significant representation of cardiovascular development functions and angiogenesis in CPC exosomes, and RNAseq analysis yielded about 350 different miRNAs; among the exo-miRSEL population, miR-935 was confirmed as the miRNA most significantly up-regulated; interestingly, miR-935 was also found to be preferentially expressed in mouse primary cardiac Bmi1+high CPC, a population highly enriched in progenitors. Furthermore, it was found that transfection of an miR-935 antagomiR combined with oxidative stress treatment provoked a significant increment both in apoptotic and necrotic populations, whereas transfection of a miR-935 mimic did not modify the response. Conclusion. miR-935 is a highly differentially expressed miRNA in exo-miRSEL, and its expression reduction promotes oxidative stress-associated apoptosis. MiR-935, together with other exosomal miRNA members, could counteract oxidative stress-related apoptosis, at least in CPC surroundings.

The Vascular Niche for Adult Cardiac Progenitor Cells.

Research on cardiac progenitor cell populations has generated expectations about their potential for cardiac regeneration capacity after acute myocardial infarction and during physiological aging; however, the endogenous capacity of the adult mammalian heart is limited. The modest efficacy of exogenous cell-based treatments can guide the development of new approaches that, alone or in combination, can be applied to boost clinical efficacy. The identification and manipulation of the adult stem cell environment, termed niche, will be critical for providing new evidence on adult stem cell populations and improving stem-cell-based therapies. Here, we review and discuss the state of our understanding of the interaction of adult cardiac progenitor cells with other cardiac cell populations, with a focus on the description of the B-CPC progenitor population (Bmi1+ cardiac progenitor cell), which is a strong candidate progenitor for all main cardiac cell lineages, both in the steady state and after cardiac damage. The set of all interactions should be able to define the vascular cardiac stem cell niche, which is associated with low oxidative stress domains in vasculature, and whose manipulation would offer new hope in the cardiac regeneration field.

Osteoprotegerin Is a Better Predictor for Cardiovascular and All-Cause Mortality than Vascular Calcifications in a Multicenter Cohort of Patients on Peritoneal Dialysis.

The purpose of this study was to compare vascular calcification (VC), serum osteoprotegerin (OPG) levels, and other biochemical markers to determine their value as available predictors of all-cause and cardiovascular (CV) mortality in patients on peritoneal dialysis (PD). A total of 197 patients were recruited from seven dialysis centers in Mexico City. VC was assessed with multi-slice computed tomography, measured using the calcification score (CaSc). OPG, albumin, calcium, hsC-reactive protein, phosphorous, osteocalcin, total alkaline phosphatase, and intact parathormone were also analyzed. Follow-up and mortality analyses were assessed using the Cox regression model. The mean age was 43.9 ± 12.9 years, 64% were males, and 53% were diabetics. The median OPG was 11.28 (IQR: 7.6−17.4 pmol/L), and 42% of cases had cardiovascular calcifications. The median VC was 424 (IQR:101−886). During follow-up (23 ± 7 months), there were 34 deaths, and 44% were cardiovascular in origin. In multivariable analysis, OPG was a significant predictor for all-cause (HR 1.08; p < 0.002) and CV mortality (HR 1.09; p < 0.013), and performed better than VC (HR 1.00; p < 0.62 for all-cause mortality and HR 1.00; p < 0.16 for CV mortality). For each mg/dL of albumin-corrected calcium, there was an increased risk for CV mortality, and each g/dL of albumin decreased the risk factor for all-cause mortality. OPG levels above 14.37 and 13.57 pmol/L showed the highest predictive value for all-cause and CV mortality in incident PD patients and performed better than VC.

Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells.

Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.

Independent Evolution Has Led to Distinct Genomic Signatures in Dutch Elm Disease-Causing Fungi and Other Vascular Wilts-Causing Fungal Pathogens.

Vascular wilts are important diseases caused by plant pathogenic fungi that result in the rapid death of their plant hosts. This is due to a systemic defense mechanism whereby the plant induces the compartmentalization of the infected vascular system in order to reduce the propagation of the fungus. The ascomycete class Sordariomycetes contains several species that cause vascular wilts in diverse plant hosts, and they can be classified into four taxonomic orders. The genetic mechanisms of pathogenesis have already been investigated in Fusarium and Verticillium species, but they have not yet been compared with other well-known wilt-causing species, especially fungi causing oak wilt or Dutch elm disease (DED). Here we analyzed 20 whole genome assemblies of wilt-causing fungi together with 56 other species using phylogenetic approaches to trace expansions and contractions of orthologous gene families and gene classes related to pathogenicity. We found that the wilt-causing pathogens evolved seven times, experiencing the largest fold changes in different classes of genes almost every time. However, some similarities exist across groups of wilt pathogens, particularly in Microascales and Ophiostomatales, and these include the common gains and losses of genes that make up secondary metabolite clusters (SMC). DED pathogens do not experience large-scale gene expansions, with most of the gene classes, except for some SMC families, reducing in number. We also found that gene family expansions in the most recent common ancestors of wilt pathogen groups are enriched for carbohydrate metabolic processes. Our study shows that wilt-causing species evolve primarily through distinct changes in their repertoires of pathogenicity-related genes and that there is the potential importance of carbohydrate metabolism genes for regulating osmosis in those pathogens that penetrate the plant vascular system.

Vitamin D receptor gene, biochemical bone markers and bone mineral density in Mexican women on dialysis.

BACKGROUND: The influence of the Bsm1 polymorphism of the vitamin D receptor (VDR) gene on mineral and bone disorders in chronic kidney disease (CKD) is still under discussion. The aim of this study was to analyse the relationship between VDR polymorphism, bone mineral density (BMD), biochemical bone markers and clinical factors in women on peritoneal dialysis (PD) and haemodialysis (HD). METHODS: In a cross-sectional study, 197 women (42 +/- 10 years; 25% with diabetes mellitus (DM); body mass index (BMI) 25.26 +/- 4.77 kg/m(2)) treated by PD (72%) or HD (28%) underwent measurements of BMD (measured at the calcaneus by quantitative ultrasound; expressed as T- and Z-scores) and plasma total calcium (tCa), intact parathyroid hormone 1-84 (iPTH), phosphorus, albumin, glucose, osteoprotegerin (OPG), fetuin-A, intact osteocalcin-49 and N-MID fragment 1-43 aa (N-MID osteocalcin) N-terminal propeptide of type 1 procollagen (PINP) and C-terminal telopeptide-beta aspartic acid (BCL). DNA was extracted from peripheral blood. PCR products were digested with Bsm1 to analyse VDR polymorphism. RESULTS: The Z-score of BMD was -1.1 +/- 1.03. According to the values of osteopenia (T-score = -1.0), patients with higher BMD were younger, had lower frequency of amenorrhoea and diabetes and had higher serum creatinine and fetuin levels as well as lower levels of PINP. In a stepwise multivariate logistics analysis, osteopenia was associated with presence of genotype BB+Bb (OR = 3.26, P < or = 0.003) and age (OR = 0.95, P = 0.050). According to the B allele, bb: n = 126 (64%) and BB+Bb: n = 71(36%), group bb had significantly higher mean Z-scores (-0.97 +/- 1.0 vs -1.3+/-0.92; P < or = 0.021). CONCLUSIONS: The high frequency of osteopenia observed in female CKD patients on dialysis is associated with age and genetic predisposition as revealed by its association to the Bsm1 VDR polymorphism.

State of the Art of Family Quality of Life in Early Care and Disability: A Systematic Review.

Background: In recent years, there has been a growing international interest in family quality of life The objective of this systematic review is to understand and analyze the conceptualization of the quality of life of families with children with disabilities between 0 and 6 years of age, the instruments for their measurement and the most relevant research results. Method: A bibliographic search was conducted in the Web of Science, Scopus and Eric databases of studies published in English and Spanish from 2000 to July 2019 focused on "family quality of life" or "quality of family life" in the disability field. A total of 63 studies were selected from a total of 1119 and analyzed for their theoretical and applied contributions to the field of early care. Results: The functional conceptualization of family quality of life predominates in this area, and a nascent and enriching holistic conceptualization is appreciated. There are three instruments that measure family quality of life in early care, although none of them is based on unified theory of FQoL; none of them focus exclusively on the age range 0-6 nor do they cover all disabilities. Conclusions: The need to deepen the dynamic interaction of family relationships and to understand the ethical requirement that the methods used to approach family quality of life respect the holistic nature of the research is noted.

The role of services content for manufacturing competitiveness: A network analysis.

This paper explores the phenomenon of international servicification of manufacturing from the period 1995 to 2011. By applying empirical techniques of Social Network Analysis and graph theory, we find that the network of flows of intermediate services embodied in manufacturing exports is still slightly dense and would not correspond to a traditional centre-periphery structure. The mapping shows a numerous, highly cohesive group of countries, with China, the USA and Germany as central economies and an increasing leading role of Asian economies, which would indicate their commitment to upgrading within global value chains. We go a step further by empirically analysing the impact of the countries' centrality in the global network of intermediate services on manufacturing competitiveness. Our findings reveal that, together with the level of embodiment of intermediate services into manufacturing exports, who the providers of those services inputs are is a key determining factor for manufacturing competitiveness.

Pathogenic perspectives for the role of inflammation in diabetic nephropathy.

Diabetes and its complications have become a public health problem. One of the most important complications is diabetic nephropathy, which is nowadays the main cause of chronic renal failure. In spite of our greater understanding of this complication, the intimate mechanisms leading to the development and progression of renal injury are not well understood. New perspectives in activated innate immunity and inflammation appear to be relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including adipokines, Toll-like receptors, chemokines, adhesion molecules and pro-inflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy.

Association of tumor necrosis factor-alpha with early target organ damage in newly diagnosed patients with essential hypertension.

OBJECTIVES: To investigate the relationship between inflammatory parameters [high-sensitivity C-reactive protein (hs-CRP), serum tumor necrosis factor-alpha (TNF-alpha) and urinary TNF-alpha] with subclinical cardiac and renal markers of early target organ damage (TOD) in essential hypertension. METHODS: Preclinical TOD [left ventricular hypertrophy (LVH) and microalbuminuria (MAB)] was evaluated in 40 newly diagnosed never-treated patients with essential hypertension. Serum and urinary TNF-alpha and hs-CRP were measured as inflammatory parameters. Twenty-one BMI-matched and sex-matched normotensive, healthy individuals were included as control group. RESULTS: The serum levels of hs-CRP and the urinary TNF-alpha excretion were higher in hypertensive patients with MAB, whereas patients with LVH presented higher levels of urinary TNF-alpha. The only difference between hypertensive patients without TOD and healthy controls was the higher urinary excretion of TNF-alpha. Partial correlation analysis showed a significant association between urinary albumin excretion (UAE) and systolic blood pressure (r=0.62, P<0.0001), hs-CRP (r=0.64, P<0.001), urinary TNF-alpha (r=0.55, P=0.001) and Cornell product (r=0.33, P<0.05), whereas the Cornell product was related to UAE (r=0.34, P<0.05), urinary TNF-alpha (r=0.45, P<0.01), and hs-CRP (r=0.32, P<0.05). Multiple regression analysis demonstrated that the parameters independently correlated with UAE were mean blood pressure, Cornell product, hs-CRP and urinary TNF-alpha (adjusted R2=0.77, P<0.001), whereas UAE, urinary TNF-alpha and hs-CRP were independently correlated with Cornell product (adjusted R2=0.66, P<0.001). Multiple logistic regression analysis with TOD as the dependent variable showed that hs-CRP [2.24 (1.17-4.28), P<0.05] and urinary TNF-alpha [1.21 (1.02-1.44), P<0.05] were independently related to TOD. CONCLUSION: Urinary TNF-alpha is independently correlated with UAE and Cornell product in essential hypertension, suggesting that inflammation may participate in the development of TOD. In addition, urinary excretion of TNF-alpha might be an early marker of preclinical TOD in hypertensive patients. Finally, these results may be a basis to study the effect of the blockade of TNF-alpha activity on the development and progression of TOD in essential hypertension.

Influence of renal involvement on peripheral blood mononuclear cell expression behaviour of tumour necrosis factor-alpha and interleukin-6 in type 2 diabetic patients.

BACKGROUND: Type 2 diabetes is associated with a high cardiovascular risk, which is even increased if renal damage is superimposed. Peripheral blood mononuclear cells (PBMCs) and pro-inflammatory cytokines are key factors linking type 2 diabetes and atherosclerosis. We investigated the influence of renal damage on serum, urinary and PBMCs expression behavior of TNF-alpha and IL-6 in these patients. METHODS: PBMCs were isolated by density gradient centrifugation (Ficoll-Paque method) from fasting blood samples of 22 non-diabetic control subjects and 78 diabetic patients with normal renal function and different stages of diabetic nephropathy (18 with normoalbuminuria, 29 with microalbuminuria and 31 with macroalbuminuria). Expression levels of TNF-alpha and IL-6 were analyzed by real-time quantitative RT-PCR. Serum and urinary TNF-alpha and IL-6 concentrations were measured by a solid-phase, chemiluminescent immunometric assay. RESULTS: The mean percent increases in the serum and urinary levels of TNF-alpha and IL-6 in diabetic patients with respect to control subjects were 176% (P < 0.0001), 250% (P < 0.0001), 114% (P < 0.0001) and 39.6% (P = 0.01), respectively. The mRNA expression level of TNF-alpha was higher by 68.8% (P < 0.001) and IL-6 mRNA levels were higher by 64.1% (P < 0.001) with respect to non-diabetic controls. TNF-alpha mRNA expression in patients with macroalbuminuria was higher by 84.8% with respect to subjects with normalbuminuria (P < 0.001) and by 29% with respect to individuals with microalbuminuria (P < 0.05). Likewise, microalbuminuric patients showed a 44.5% increase in TNF-alpha mRNA expression compared to subjects with normoalbuminuria (P < 0.05). Concerning IL-6, the mRNA expression levels of this cytokine was higher by 63.1% with respect to normoalbuminuric subjects (P < 0.01), and by 23.1% with respect to patients with microalbuminuria (P < 0.05). However, with respect to controls, diabetic patients with normoalbuminuria had similar serum TNF-alpha and urinary excretion of IL-6, without any differences in the mRNA expression levels of these cytokines in PBMCs. Partial correlation and multiple regression analysis using TNF-alpha and IL-6 mRNA levels as the dependent variables showed that urinary albumin excretion (UAE) was direct and independently associated with the expression profile of these pro-inflammatory cytokines in PBMCs. CONCLUSIONS: These data show for the first time the relationship between inflammatory activation of PBMCs (reflected by enhanced mRNA expression of TNF-alpha and IL-6) and renal involvement (reflected by increased UAE) in type 2 diabetic patients. These results provide potential insights for the increased inflammation, accelerated atherosclerosis and cardiovascular risk associated with nephropathy in type 2 diabetes.

High Prevalence of Diastolic Dysfunction in Incident Patients on Peritoneal Dialysis: Association with Low Thyroid Hormones.

BACKGROUND/AIMS: Diastolic dysfunction (DD) and low levels of thyroid hormones (TH) are frequent found in chronic kidney disease; both are associated with all-cause and cardiovascular mortality. However, a link between them has not yet been established. The aim of this study was to analyze DD as a surrogate marker of fibrosis and its association with TH in incident patients on peritoneal dialysis (PD). METHODS: A cross-sectional study with 183 incident patients on PD with preserved ejection fraction was performed. Clinical and demographic data were registered. Serum total and free (t/f) triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone levels were determined by RIA kits, albumin and high-sensitivity C-reactive protein by conventional assays. Transthoracic 2D echocardiogram was performed for evaluation of left ventricular (LV) mass and ejection fraction. DD was evaluated using pulsed-wave tissue Doppler imaging. RESULTS: Patients were 43 ± 12, 42% with diabetes mellitus (DM). Some degree of DD was found in 62% of patients; 18% had grade I DD, 8% grade II DD and 36% grade III DD. Patients with grade III DD were more likely to have diabetes, older, high LV mass and low serum albumin, t/fT3 and tT4 levels. In logistic multivariate regression analysis, it was found that diabetes (B = -0.86, 95% CI 0.182-0.992, p < 0.05), hypertension (B = -0.95, 95% CI 0.184-0.817, p = 0.01) and tT3 (B = -1.94, 95% CI 0.023-0.876, p < 0.05) were associated with grade III DD. CONCLUSIONS: High prevalence of grade III DD was found in incident patients on PD. In addition to DM and hypertension, tT3 was found to be an independent risk factor for grade III DD and more studies are needed to understand the reasons as to why this association is present.

Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients. / La disminución de triyodotironina se asocia con la elevación del péptido natriurético cerebral N-terminal y con la mortalidad en pacientes en diálisis.

BACKGROUND: Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. MATERIAL AND METHODS: TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. RESULTS: Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. CONCLUSIONS: Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality.