EEF1A1 transcription cofactor gene polymorphism is associated with muscle gene expression and residual feed intake in Nelore cattle.

Cis-acting effects of noncoding variants on gene expression and regulatory molecules constitute a significant factor for phenotypic variation in complex traits. To provide new insights into the impacts of single-nucleotide polymorphisms (SNPs) on transcription factors (TFs) and transcription cofactors (TcoF) coding genes, we carried out a multi-omic analysis to identify cis-regulatory effects of SNPs on these genes' expression in muscle and describe their association with feed efficiency-related traits in Nelore cattle. As a result, we identified one SNP, the rs137256008C > T, predicted to impact the EEF1A1 gene expression (ß = 3.02; P-value = 3.51E-03) and the residual feed intake trait (ß = - 3.47; P-value = 0.02). This SNP was predicted to modify transcription factor sites and overlaps with several QTL for feed efficiency traits. In addition, co-expression network analyses showed that animals containing the T allele of the rs137256008 SNP may be triggering changes in the gene network. Therefore, our analyses reinforce and contribute to a better understanding of the biological mechanisms underlying gene expression control of feed efficiency traits in bovines. The cis-regulatory SNP can be used as biomarker for feed efficiency in Nelore cattle.

Aspects Towards the Anastomotic Healing in Crohn's Disease: Clinical Approach and Current Gaps in Research.

Anastomotic leakage is a major complication in gastrointestinal and colorectal surgery and its occurrence increases morbidity and mortality. Its incidence is even higher in Crohn's disease surgeries. Several authors have identified factors involved in the pathophysiology of anastomotic leak in the literature, aiming to reduce its occurrence and, therefore, improve its surgical treatment. Surgical technique is the most discussed topic in studies on guiding the performance of side-to-side stapled anastomosis. Preoperative nutritional therapy also has been shown to reduce the risk of anastomotic leakage. Other factors remain controversial - immunomodulator use and biologic therapy, antibiotics, and gut microbiota - with studies showing a reduction in the risk of complication while other studies show no correlation. Although mesenteric adipose tissue has been related to disease recurrence, there is no evidence in the literature that it is related to a higher risk of anastomotic leakage. Further exploration on this topic is necessary, including prospective research, to support the development of techniques to prevent anastomotic leakage, in this way benefiting the inflammatory bowel disease patients who have to undergo a surgical procedure.

Genetic identification of a rabies virus from an insectivorous bat in an urban area of Rio Grande do Sul, Brazil.

In Latin America, hematophagous bats are the main reservoirs of rabies virus (RABV) to livestock, to other mammals and, occasionally, to human. Nonetheless, reports of exposure of human and pets to RABV upon aggression by non-hematophagous bats are increasing, possibly facilitated by the synanthropic habits of these bats. We, herein, report the detection and genetic identification of a RABV recovered from an insectivorous bat found sick in a student housing building at the Federal University of Santa Maria, Southern Brazil. Taxonomic characterization identified the captured bat as a member of the genus Nyctinomops, family Molossidae, the group of insectivorous bats. Brain fragments of the bat were positive for RABV antigens by fluorescent antibody test (FAT) and for sequences of the nucleoprotein (N) gene by RT-PCR. The N amplicon was submitted to nucleotide sequencing and analysis, showing that the consensus sequences (SV 33/19) had high identity with RABV sequences of insectivorous bats deposited in GenBank. At phylogenetic tree, the N gene sequences of SV 33/19 clustered with RABV recovered from Nyctinomops laticaudatus, Molossus molossus, and Tadarida lauticaudata bats, and a part of RABV variant 3, 4, and 6, that correspond to Desmodus rotundus, Tadarida brasiliensis, and Lasiurus cinereus, respectively. Although no direct human or domestic animal exposure has been reported, this case strengthens the need for a continuous rabies vaccination in pets in the surrounding areas, since non-hematophagous bats may serve as source of infection for these animals. These findings also call attention for continuous monitoring of populations of synanthropic bats to avoid/prevent human exposure.

Evidence of macrophage modulation in the mouse pubic symphysis remodeling during the end of first pregnancy and postpartum.

In mouse pregnancy, pubic symphysis (PS) remodels into an elastic interpubic ligament (IpL) in a temporally regulated process to provide safe delivery. It restores at postpartum to assure reproductive tract homeostasis. Recently, macrophage localization in the IpL and dynamic changes in the expression of inflammatory mediators observed from the end of pregnancy (D18, D19) to early days postpartum (1dpp, 3dpp) highlighted the necessity of the identification of the key molecules involved in innate immune processes in PS remodeling. Therefore, this study uses morphological and high-sensitivity molecular techniques to identify both macrophage association with extracellular matrix (ECM) remodeling and the immunological processes involved in PS changes from D18 to 3dpp. Results showed macrophage association with active gelatinases and ECM components and 25 differentially expressed genes (DEGs) related to macrophage activities in interpubic tissues from D18 to 3dpp. Additionally, microarray and proteomic analysis showed a significant association of interpubic tissue DEGs with complement system activation and differentially expressed proteins (DEPs) with phagocytosis, highlighting the involvement of macrophage-related activities in mouse PS remodeling. Therefore, the findings suggest that PS ECM remodeling is associated with evidence of macrophage modulation that ensures both IpL relaxation and fast PS recovery postpartum for first labor.

Exploring the mechanism of PPARγ phosphorylation mediated by CDK5.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor with a key role in metabolic processes and is target of CDK5 kinase phosphorylation at S245 (S273 in PPARγ isoform 2), thereby inducing insulin resistance. A remarkable effort has been addressed to find PPARγ ligands that inhibit S245 phosphorylation, but the poor understanding in this field challenges the design of such ligands. Here, through computational and biophysical methods, we explored an experimentally validated model of PPARγ-CDK5 complex, and we presented K261, K263 or K265, which are conserved in mammals, as important anchor residues for this interaction. In addition, we observed, from structural data analysis, that PPARγ ligands that inhibit S245 phosphorylation are not in direct contact with these residues; but induce structural modifications in PPARγ:CDK5/p25 interface. In summary, our PPARγ and CDK5/p25 interaction analyses open new possibilities for the rational design of novel inhibitors that impair S245 phosphorylation.

Ketoprofen-loaded rose hip oil nanocapsules attenuate chronic inflammatory response in a pre-clinical trial in mice.

This study aimed to develop nanocapsules containing ketoprofen using rose hip oil (Keto-NC) as oil core, and to evaluate their anti-inflammatory activity in acute and chronic ear edema models in mice. Physicochemical characterization, drug release, photostability and cytotoxicity assays were performed for the developed Keto-NC formulations and compared to ketoprofen-loaded nanocapsules using medium chain triglycerides as oil core (Keto-MCT-NC). Anti-inflammatory activity of orally delivered KP (Ketoprofen-free; 10 mg.kg-1) or Keto-NC (2.5; 5; 10 mg.kg-1) was assessed in mouse acute and chronic ear edema induced by croton oil (CO). Edema histological characteristics were determined by H&E stain, and redox parameters were analyzed in blood plasma and erythrocytes. Keto-MCT-NC and Keto-NC did not exhibit differences regarding physicochemical parameters, including size diameters, polydispersity index, pH, Ketoprofen content, and encapsulation efficiency. However, Keto-NC, which contains rose hip oil as lipid core, decreased drug photodegradation under UVC radiation when compared to Keto-MCT-NC. KP or Keto-NC were not cytotoxic to keratinocyte cultures and produced equal edema inhibition in the acute protocol. Conversely, in the chronic protocol, Keto-NC was more effective in reducing edema (~60-70% on 7-9th days of treatment) when compared to KP (~40% on 8-9th days of treatment). This result was confirmed by histological analysis, which indicated reduction of edema and inflammatory infiltrate. A sub-therapeutic dose of Keto-NC (5 mg.kg-1) significantly reduced edema when compared to control. Finally, KP and Keto-NC exhibited similar effects on redox parameters, suggesting that the advantages associated with Ketoprofen nanoencapsulation did not involve oxidative stress pathways. The results showed that Keto-NC was more efficient than KP in reducing chronic inflammation. These data may be important for the development of strategies aiming treatment of chronic inflammatory diseases with fewer adverse effects.

Phrixotrix luciferase and 6'-aminoluciferins reveal a larger luciferin phenolate binding site and provide novel far-red combinations for bioimaging purposes.

How the unique luciferase of Phrixothrix hirtus (PxRE) railroad worm catalyzes the emission of red bioluminescence using the same luciferin of fireflies, remains a mystery. Although PxRE luciferase is a very attractive tool for bioanalysis and bioimaging in hemoglobin rich tissues, it displays lower quantum yield (15%) when compared to green emitting luciferases (>40%). To identify which parts of PxRE luciferin binding site (LBS) determine bioluminescence color, and to develop brighter and more red-shifted emitting luciferases, we compared the effects of site-directed mutagenesis and of larger 6'-substituted aminoluciferin analogues (6'-morpholino- and 6'-pyrrolidinyl-LH) on the bioluminescence properties of PxRE and green-yellow emitting beetle luciferases. The effects of mutations in the benzothiazolyl and thiazolyl parts of PxRE LBS on the KM and catalytic efficiencies, indicated their importance for luciferin binding and catalysis. However, the absence of effects on the bioluminescence spectrum indicated a less interactive LBS in PxRE during light emission. Mutations at the bottom of LBS of PxRE blue-shifted the spectra and increased catalytic efficiency, suggesting that lack of interactions of this part of LBS with excited oxyluciferin phenolate underlie red light emission. The much higher bioluminescence activity and red-shifted spectra of PxRE luciferase with 6'-morpholino- (634 nm) and 6'-pyrrolidinyl-luciferins (644 nm), when compared to other beetle luciferases, revealed a larger luciferin phenolate binding pocket. The size and orientation of the side-chains of L/I/H348 are critical for amino-analogues accommodation and modulate bioluminescence color, affecting the interactions and mobility of excited oxyluciferin phenolate. The PxRE luciferase and 6'-aminoluciferins provide potential far-red combinations for bioimaging applications.

Impact of root canal preparation performed by ProTaper Next or Reciproc on the quality of life of patients: a randomized clinical trial.

AIM: To compare the impact of the two different root canal preparation systems on the quality of life of patients and correlate postoperative pain with the impact on quality of life. METHODOLOGY: A randomized clinical trial was conducted with 58 patients allocated into two groups based on the root canal preparation system employed: ProTaper Next (PN) or Reciproc (R). Data collection involved the administration of a questionnaire addressing demographic and clinical characteristics, the OHIP-14 (quality of life) and a visual analog scale (pain). The latter two were the outcomes of interest and were administered in the first 24 h after root canal treatment. The data were submitted to descriptive analysis, bivariate analysis, Poisson univariate and multiple regression, and Spearman's correlation test, with a 5% significance level. RESULTS: A greater frequency of impact after treatment was found for the items 'uncomfortable to eat food' and 'felt self-conscious'. No significant difference between groups was found regarding the severity of impact for total OHIP-14 score or any of the domain scores. CONCLUSIONS: The two root canal preparation systems exerted a similar impact on quality of life. Postoperative pain was correlated with impact on quality of life, affecting chewing function, self-consciousness and stress. Thus, it is important for dentists to provide care capable of preventing or treating the negative consequences of such therapy.

The proton and metal binding sites responsible for the pH-dependent green-red bioluminescence color tuning in firefly luciferases.

Firefly luciferases produce yellow-green light under physiological and alkaline conditions, however at acidic pH, higher temperatures or in the presence of heavy metals the color changes to red, a property called pH-sensitivity. Despite many decades of studies, the proton and metal binding sites responsible for pH-sensitivity remain enigmatic. Previously we suggested that the salt bridge E311/R337 keeps a closed conformation of the luciferin phenolate binding site. Here we further investigated the effect of this salt bridge and mutations of the neighbor residues H310 and E/N354, on metal and pH-sensitivity of firefly luciferases emitting distinct bioluminescence colors (Cratomorphus distinctus: 548 nm; Macrolampis sp2: 569 nm). The substitutions of H310 and E/N354 modulate metal sensitivity, whereas the carboxylate of E311 may work as the catalytic base essential for green bioluminescence and pH-sensitivity. Modeling studies showed that H310, E311 and E354 side-chains coordinate Zinc, constituting the metal binding site and the pH-sensor. Electrostatic potential and pKa calculations suggest that the external couple H310/E354 is affected by pH, whereas E311/R337 make a stabilized internal pair which retains excited oxyluciferin ejected proton near its phenolate group into a high energy state, promoting yellow-green bioluminescence. Protonation or metal binding weaken these electrostatic gates and their ability to retain the excited oxyluciferin released proton near its phenolate, promoting red light emission.

The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L.

Myosin Va (MyoVa) is an actin-based molecular motor abundantly found at the centrosome. However, the role of MyoVa at this organelle has been elusive due to the lack of evidence on interacting partners or functional data. Herein, we combined yeast two-hybrid screen, biochemical studies and cellular assays to demonstrate that MyoVa interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning. MyoVa binds to the C2 domains of RPGRIP1L via residues located near or in the Rab11a-binding site, a conserved site in the globular tail domain (GTD) from class V myosins. According to proximity ligation assays, MyoVa and RPGRIP1L can interact near the cilium base in ciliated RPE cells. Furthermore, we showed that RPE cells expressing dominant-negative constructs of MyoVa are mostly unciliated, providing the first experimental evidence about a possible link between this molecular motor and cilia-related processes.

Allele- and parent-of-origin-specific effects on expression of the KCNJ11 gene: A candidate for meat tenderness in cattle.

In contrast to the Mendelian inheritance model, parental alleles can contribute unequally to gene expression, which may result in phenotypic variance among individuals and bias in the predicted additive effect of molecular markers associated with production traits. Given the need to understand the effects of allelic variation and parent-of-origin effects on the expression of genes with a commercial interest in cattle, we analyzed the expression of KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), which was previously described as a functional candidate gene for meat tenderness. Allele-specific and parent-of-origin-dependent expression of this gene were assessed in bovine muscle using the rs379610823 single nucleotide polymorphism as a reference. Biallelic expression was observed; however, the T allele was expressed at significantly higher levels than the C allele. Furthermore, increased expression of KCNJ11 was found in animals harboring the maternal T allele. This study is the first to describe the differential allelic expression of bovine KCNJ11. Our findings are important for understanding the mechanisms that underlie the pattern of KCNJ11 expression and its potential impact on the phenotypic variation of meat tenderness in Nelore beef cattle. This reinforces the need for further investigation of allelic- and parent-of-origin expression deviation in genetic markers eligible for the selection of target traits.

Implant-Abutment Contact Surfaces and Microgap Measurements of Different Implant Connections Under 3-Dimensional X-Ray Microtomography.

PURPOSE: The presence of a microgap between implant and abutment could produce a bacterial reservoir which could interfere with the long-term health of the periimplant tissues. The aim of this article was to evaluate, by x-ray 3-dimensional microtomography, implant-abutment contact surfaces and microgaps at the implant-abutment interface in different types of implant-abutment connections. MATERIALS AND METHODS: A total of 40 implants were used in this in vitro study. Ten implants presented a screw-retained internal hexagon abutment (group I), 10 had a Morse Cone taper internal connection (group II), 10 another type of Morse Cone taper internal connection (group III), and 10 had a screwed trilobed connection (group IV). RESULTS: In both types of Morse Cone internal connections, there was no detectable separation at the implant-abutment in the area of the conical connection, and there was an absolute congruity without any microgaps between abutment and implant. No line was visible separating the implant and the abutment. On the contrary, in the screwed abutment implants, numerous gaps and voids were present. CONCLUSIONS: The results of this study support the hypothesis that different types of implant-abutment joints are responsible for the observed differences in bacterial penetration.

A single nucleotide polymorphism in NEUROD1 is associated with production traits in Nelore beef cattle.

Feed efficiency and carcass characteristics are late-measured traits. The detection of molecular markers associated with them can help breeding programs to select animals early in life, and to predict breeding values with high accuracy. The objective of this study was to identify polymorphisms in the functional and positional candidate gene NEUROD1 (neurogenic differentiation 1), and investigate their associations with production traits in reference families of Nelore cattle. A total of 585 steers were used, from 34 sires chosen to represent the variability of this breed. By sequencing 14 animals with extreme residual feed intake (RFI) values, seven single nucleotide polymorphisms (SNPs) in NEUROD1 were identified. The investigation of marker effects on the target traits RFI, backfat thickness (BFT), ribeye area (REA), average body weight (ABW), and metabolic body weight (MBW) was performed with a mixed model using the restricted maximum likelihood method. SNP1062, which changes cytosine for guanine, had no significant association with RFI or REA. However, we found an additive effect on ABW (P ≤ 0.05) and MBW (P ≤ 0.05), with an estimated allele substitution effect of -1.59 and -0.93 kg0.75, respectively. A dominant effect of this SNP for BFT was also found (P ≤ 0.010). Our results are the first that identify NEUROD1 as a candidate that affects BFT, ABW, and MBW. Once confirmed, the inclusion of this SNP in dense panels may improve the accuracy of genomic selection for these traits in Nelore beef cattle as this SNP is not currently represented on SNP chips.

Genetic variants in glucocorticoid and mineralocorticoid receptors are associated with concentrations of plasma cortisol, muscle glycogen content, and meat quality traits in male Nellore cattle.

The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are key components in the regulation of the hypothalamic-pituitary-adrenal neuroendocrine axis and coordinate the physiological response to stress agents to reestablish homeostasis. Genetic variations of GR (NR3C1) and MR (NR3C2) genes could explain the alterations in animals to adapt to challenges, and therefore, their influence on production traits. The present study aimed to identify single-nucleotide polymorphisms (SNPs) in the bovine NR3C1 and NR3C2 genes and explore their associations to relevant traits of beef cattle production. Genotypes and phenotypes were collected from 241 male Nellore cattle (119 noncastrated and 122 castrated surgically) with an average of 24 ± 1.2 mo of age and live weight of 508 ± 39 kg. The traits evaluated were concentrations of plasma adrenocorticotropic hormone (ACTH) and cortisol, muscle glycogen and lactate content, and pH, color, cooking loss, and shear force of longissimus thoracis measured on the 1st, 7th, and 14th days postmortem. Five SNPs were identified, 2 in the NR3C1 gene and 3 in the NR3C2 gene. There was an associative relationship between the SNP NR3C1_1 g.3293A>G and postmortem plasma concentration of cortisol (P = 0.0008). The SNPs NR3C2_1 g.115T>C and NR3C2_2 g.570T>C were associated with muscle glycogen content (P = 0.0306 and P = 0.0158), postmortem plasma concentration of ACTH (P = 0.0118 and P = 0.0095), and cooking loss of the steak aged 1 d (P = 0.0398 and P = 0.0423). Haplotype analysis showed associations of GR haplotypes with postmortem plasma concentrations of cortisol and MR haplotypes with meat color, cooking losses, muscle glycogen content, and plasma concentrations of ACTH. The associations observed in the present study show that SNPs in GR and MR genes are related with changes of hypothalamic-pituitary-adrenal axis activity and metabolic profile in cattle, leading to individual variation in meat quality traits.

Hyperbaric oxygen therapy induces kidney protection in an ischemia/reperfusion model in rats.

Ischemia/reperfusion (I/R) injury remains a major cause of graft dysfunction, which impacts short- and long-term follow-up. Hyperbaric oxygen therapy (HBO), through plasma oxygen transport, has been currently used as an alternative treatment for ischemic tissues. The aim of this study was to analyze the effects of HBO on kidney I/R injury model in rats, in reducing the harmful effect of I/R. The renal I/R model was obtained by occluding bilateral renal pedicles with nontraumatic vascular clamps for 45 minutes, followed by 48 hours of reperfusion. HBO therapy was delivered an hypebaric chamber (2.5 atmospheres absolute). Animals underwent two sessions of 60 minutes each at 6 hours and 20 hours after initiation of reperfusion. Male Wistar rats (n = 38) were randomized into four groups: sham, sham operated rats; Sham+HBO, sham operated rats exposed to HBO; I/R, animals submitted to I/R; and I/R+HBO, I/R rats exposed to HBO. Blood, urine, and kidney tissue were collected for biochemical, histologic, and immunohistochemical analyses. The histopathological evaluation of the ischemic injury used a grading scale of 0 to 4. HBO attenuated renal dysfunction after ischemia characterized by a significant decrease in blood urea nitrogen (BUN), serum creatinine, and proteinuria in the I/R+HBO group compared with I/R alone. In parallel, tubular function was improved resulting in significantly lower fractional excretions of sodium and potassium. Kidney sections from the I/R plus HBO group showed significantly lower acute kidney injury scores compared with the I/R group. HBO treatment significantly diminished proliferative activity in I/R (P < .05). There was no significant difference in macrophage infiltration or hemoxygenase-1 expression. In conclusion, HBO attenuated renal dysfunction in a kidney I/R injury model with a decrease in BUN, serum creatinine, proteinuria, and fractional excretion of sodium and potassium, associated with reduced histological damage.

Pedigree analysis and inbreeding depression on growth traits in Brazilian Marchigiana and Bonsmara breeds.

The study of population structure by pedigree analysis is useful to identify important circumstances that affect the genetic history of populations. The intensive use of a small number of superior individuals may reduce the genetic diversity of populations. This situation is very common for the beef cattle breeds. Therefore, the objectives of the present study were to analyze the pedigree and possible inbreeding depression on traits of economic interest in the Marchigiana and Bonsmara breeds and to test the inclusion of the individual inbreeding coefficient (F(i)) or individual increases in inbreeding coefficient (ΔF(i)) in the genetic evaluation model for the quantification of inbreeding depression. The complete pedigree file of the Marchigiana breed included 29,411 animals born between 1950 and 2003. For the Bonsmara breed, the pedigree file included 18,695 animals born between 1988 and 2006. Only animals with at least 2 equivalent generations of known pedigree were kept in the analyses of inbreeding effect on birth weight, weaning weight measured at about 205 d, and BW at 14 mo in the Marchigiana breed, and on birth weight, weaning weight, and scrotal circumference measured at 12 mo in the Bonsmara breed. The degree of pedigree knowledge was greater for Marchigiana than for Bonsmara animals. The average generation interval was 7.02 and 3.19 for the Marchigiana and Bonsmara breed, respectively. The average inbreeding coefficient was 1.33% for Marchigiana and 0.26% for Bonsmara. The number of ancestors explaining 50% of the gene pool and effective population size computed via individual increase in coancestry were 13 and 97.79 for Marchigiana and 41 and 54.57 for Bonsmara, respectively. These estimates indicate reduction in genetic variability in both breeds. Inbreeding depression was observed for most of the growth traits. The model including ΔF(i) can be considered more adequate to quantify inbreeding depression. The inclusion of F(i) or ΔF(i) in the genetic evaluation model may not result in better fit to the data. A genetic evaluation with simultaneous estimation of inbreeding depression can be performed in Marchigiana and Bonsmara breeds, providing additional information to producers and breeders.

Identical sequence patterns in the ends of exons and introns of human protein-coding genes

Intron splicing is one of the most important steps involved in the maturation process of a pre-mRNA. Although the sequence profiles around the splice sites have been studied extensively, the levels of sequence identity between the exonic sequences preceding the donor sites and the intronic sequences preceding the acceptor sites has not been examined as thoroughly. In this study we investigated identity patterns between the last 15 nucleotides of the exonic sequence preceding the 5' splice site and the intronic sequence preceding the 3' splice site in a set of human protein-coding genes that do not exhibit intron retention. We found that almost 60% of consecutive exons and introns in human protein-coding genes share at least two identical nucleotides at their 3' ends and, on average, the sequence identity length is 2.47 nucleotides. Based on our findings we conclude that the 3' ends of exons and introns tend to have longer identical sequences within a gene than when being taken from different genes. Our results hold even if the pairs are non-consecutive in the transcription order.

A safety and feasibility study of cell therapy in dilated cardiomyopathy

The aim of this study was to determine if bone marrow mononuclear cell (BMMC) transplantation is safe for moderate to severe idiopathic dilated cardiomyopathy (IDC). Clinical trials have shown that this procedure is safe and effective for ischemic patients, but little information is available regarding non-ischemic patients. Twenty-four patients with IDC, optimized therapy, age 46 ± 11.6 years, 17 males, NYHA classes II-IV, and left ventricular ejection fraction <35 percent were enrolled in the study. Clinical evaluation at baseline and 6 months after stem cell therapy to assess heart function included echocardiogram, magnetic resonance imaging, cardiopulmonary test, Minnesota Quality of Life Questionnaire, and NYHA classification. After cell transplantation 1 patient showed a transient increase in enzyme levels and 2 patients presented arrhythmias that were reversed within 72 h. Four patients died during follow-up, between 6 and 12 weeks after therapy. Clinical evaluation showed improvement in most patients as reflected by statistically significant decreases in Minnesota Quality of Life Questionnaire (63 ± 17.9 baseline vs 28.8 ± 16.75 at 6 months) and in class III-IV NYHA patients (18/24 baseline vs 2/20 at 6 months). Cardiopulmonary exercise tests demonstrated increased peak oxygen consumption (12.2 ± 2.4 at baseline vs 15.8 ± 7.1 mL·kg-1·min-1 at 6 months) and walked distance (377.2 ± 85.4 vs 444.1 ± 77.9 m at 6 months) in the 6-min walk test, which was not accompanied by increased left ventricular ejection fraction. Our findings indicate that BMMC therapy in IDC patients with severe ventricular dysfunction is feasible and that larger, randomized and placebo-controlled trials are warranted.

A safety and feasibility study of cell therapy in dilated cardiomyopathy.

The aim of this study was to determine if bone marrow mononuclear cell (BMMC) transplantation is safe for moderate to severe idiopathic dilated cardiomyopathy (IDC). Clinical trials have shown that this procedure is safe and effective for ischemic patients, but little information is available regarding non-ischemic patients. Twenty-four patients with IDC, optimized therapy, age 46 ± 11.6 years, 17 males, NYHA classes II-IV, and left ventricular ejection fraction <35% were enrolled in the study. Clinical evaluation at baseline and 6 months after stem cell therapy to assess heart function included echocardiogram, magnetic resonance imaging, cardiopulmonary test, Minnesota Quality of Life Questionnaire, and NYHA classification. After cell transplantation 1 patient showed a transient increase in enzyme levels and 2 patients presented arrhythmias that were reversed within 72 h. Four patients died during follow-up, between 6 and 12 weeks after therapy. Clinical evaluation showed improvement in most patients as reflected by statistically significant decreases in Minnesota Quality of Life Questionnaire (63 ± 17.9 baseline vs 28.8 ± 16.75 at 6 months) and in class III-IV NYHA patients (18/24 baseline vs 2/20 at 6 months). Cardiopulmonary exercise tests demonstrated increased peak oxygen consumption (12.2 ± 2.4 at baseline vs 15.8 ± 7.1 mL·kg⁻¹·min⁻¹ at 6 months) and walked distance (377.2 ± 85.4 vs 444.1 ± 77.9 m at 6 months) in the 6-min walk test, which was not accompanied by increased left ventricular ejection fraction. Our findings indicate that BMMC therapy in IDC patients with severe ventricular dysfunction is feasible and that larger, randomized and placebo-controlled trials are warranted.