Uniendo esfuerzos frente a la hipertensión arterial / Joining forces against arterial hypertension

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Influence of single nucleotide polymorphisms in the myostatin and myogenic factor 5 muscle growth-related genes on the performance traits of Marchigiana beef cattle.

The Marchigiana is famous for its large body size and favorable dressing percentage. A myostatin (MSTN) gene mutation (a G to T transversion) was identified in the breed. The homozygote "GG" yields a "normal" phenotype, the homozygote "TT" yields a double muscled body shape but sometimes causes survival problems, and the heterozygote genotype produces an extremely muscled body without defects. In practice, Marchigiana "TT" homozygotes are culled from reproduction, but the heterozygotes are chosen as sires. The objective of this study was to assess genes involved in Marchigiana muscle development to improve selection procedures. The effects of the MSTN and myogenic factor 5 (MYF5) genes on the growth and muscle traits in the Marchigiana breed were assessed. The effects of MSTN together with the genotype of the causative mutation (g.874G > T) and the effects of the two SNP in the promoter were studied (g.-371T > A and g.-805G > C). The SNP effects were evaluated in a comparison between the means of the several genotypes or for the average gene substitution and dominance effect. Two hundred forty-nine bullocks were evaluated using a performance test. At the beginning and end of the trial, the animals were weighed and their bodies were measured every 21 d up to 12 mo of age. In addition to these observations, morphological scores and the BLUP indices were estimated at the end of the performance test. The obtained results suggested that the MSTN g.874G > T and MYF5 SNP could be considered in the selection program of the Marchigiana breed. A MSTN g.874G > T genotyping service for the breeders could help to avoid the "TT" genotype and to select for the "GT" genotype. The "AA" MYF5 SNP genotype could also be selected for even if good muscle development yields a certain size reduction.

Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies.

OBJECTIVE: To compare maternal and perinatal outcomes in twin pregnancies conceived via assisted reproductive techniques (ART) compared with spontaneous twin pregnancies. STUDY DESIGN: This retrospective study examined 345 dichorionic, di-amniotic twin pregnancies (207 conceived spontaneously and 138 conceived via ART), delivered between January 2007 and June 2011 at the San Pietro Fatebenefratelli Hospital, Rome, a tertiary medical centre. Maternal and perinatal outcomes were compared. A multiple logistic regression analysis was performed to calculate risk estimates as odds ratios (OR) adjusted for maternal age, parity and systemic diseases. Patient data were obtained from a computerized database and analyzed using Statistical Package for the Social Sciences Version 17. RESULTS: Gestational age and birth weight were lower in the ART group, and preterm delivery, gestational diabetes and placental abruption were higher in the ART group compared with the spontaneous conception group. The incidence rates of respiratory complications, patent ductus arteriosus and admission to the neonatal intensive care unit were higher among ART newborns. Length of hospital stay for mothers and newborns was longer in the ART group. No differences in mode of delivery, Apgar score at 5min, congenital anomalies, perinatal mortality, and other considered pregnancy and neonatal complications were found between the two groups. Multivariate analysis adjusted for maternal age, parity and systemic diseases revealed that only the rates of placental abruption [OR 7.45, 95% confidence interval (CI) 2.05-26.98] and patent ductus arteriosus (OR 3.39, 95% CI 1.01-11.46) were significantly higher for the ART group. CONCLUSIONS: Twin pregnancies conceived via ART are at greater risk of poorer outcomes than spontaneous twin pregnancies. This may be related to the type of conception and specific negative features of subfertile patients undergoing infertility treatment.

Genomic characterization and chromosomal mapping of 5 river buffalo skeletal muscle differentiation master genes.

River buffalo (Bubalus bubalis, 2n = 50, BBU) is a species of economic relevance in a number of countries. This species shows a very peculiar biology and a great capacity for environmental adaptation. There has been an increasing economic interest as well as a growing demand for a more detailed knowledge of molecular features in this species. From this perspective we report a genomic, transcriptional and cytogenetic analysis of 5 master genes involved in skeletal muscle development. Of these 5 genes, MYOD1, MYF5, MYF6 and MYOG belong to the basic helix-loop helix protein family while MSTN belongs to the TNF-B protein family. In mammals, these genes are involved in the early stages of skeletal muscle differentiation, development and regeneration. These pivotal biological functions are finely regulated in a tissue- and temporal-specific manner. We used a comparative genomic approach to obtain the buffalo specific sequences of MYOD1 and MYF6. The nucleotide sequence similarity and the protein domain conservation of the newly obtained sequences are analysed with respect to bovine and other mammalian species showing sequence similarity. The presence of a polymorphism in MYOD1 coding sequence is described and its possible effect discussed. Using a quantitative PCR approach, we compared the level of the 5 transcripts in adult and fetal muscle. These genes were physically localised on river buffalo R-banded chromosomes by FISH using bovine genomic BAC-clones. Here, we present a genomic and cytogenetic analysis which could offer a background to better characterise the buffalo genes involved in muscle function and which may be responsible for buffalo-specific meat features.

Beneficial effects of melatonin on nicotine-induced vasculopathy.

Tobacco smoking is responsible for death of many people each year and increases the risk of developing numerous disorders, particularly cardiovascular disease and cancer. Among the components of cigarette smoke, nicotine is known to excert proatherosclerotic, prothrombotic and proangiogenic effects on vascular endothelial cells. The current study was designed to investigate the mechanisms by which nicotine induces endothelial dysfunction and further to examine whether melatonin protects against nicotine-induced vasculopathy. Four groups of male rats (controls, melatonin-treated, nicotine treated [100 microg/mL in drinking water], and nicotine plus melatonin [5 mg/kg/day] treated) were used in this study. After 28 days all the animals were killed by decapitation and the aorta was removed. We evaluated the hydroxyproline content, and the different expression of proteins involved in several types of stress (ERK1/2), in fibrosis (TGF-beta1, NF-kappaB) and in recruitment of circulating leukocytes onto the vessel wall, including intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1). These metabolic pathways are important in the development of nicotine-induced atherosclerosis and hypertension. Our results show that nicotine induces marked structural and functional alterations in the aorta. Nicotine receptor binding results in activation and phosphorylation of ERK 1/2. This enzyme, in turn, activates both TGF-beta1 and NF-kappaB; they stimulate respectively the synthesis of type I collagen, responsible of fibrosis, and moreover ICAM-1, VCAM-1 and reactive oxygen species. Based on these findings, melatonin is able to minimize the negative effects of nicotine by blocking the activation of ERK and the other signalling pathways in which this enzyme is involved.

Red wine polyphenols prevent cyclosporine-induced nephrotoxicity at the level of the intrinsic apoptotic pathway.

Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether Provinols flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with Provinols, or with CsA and Provinols simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. Provinols restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms.

Relationship between profitability and type traits and derivation of economic values for reproduction and survival traits in Chianina beef cows.

The objectives of this study were 1) to propose a profit function for Italian Chianina beef cattle; 2) to derive economic values for some biological variables in beef cows, specifically, production expressed as the number of calves born alive per year (NACY), age at the insemination that resulted in the birth of the first calf (FI), and length of productive life (LPL); and 3) to investigate the relationship between the phenotypic profit function and type traits as early predictors of profitability in the Chianina beef cattle population. The average profit was 196 Euros/(cow.yr) for the length of productive life (LPL) and was obtained as the difference between the average income of 1,375 Euros/(cow.yr) for LPL and costs of 1,178 Euros/(cow.yr) of LPL. The mean LPL was equal to 5.97 yr, so the average total phenotypic profit per cow on a lifetime basis was 1,175 Euros. A normative approach was used to derive the economic weights for the biological variables. The most important trait was the number of calves born alive (+4.03.cow(-1).yr(-1) and +24.06 Euros/cow). An increase of 1 d in LPL was associated with an increase of +0.19 Euros/(cow.yr) and +1.65 Euros/cow on a lifetime basis. Increasing FI by 1 d decreased profit by 0.42 Euros/(cow.yr) and 2.51 Euros/cow. Phenotypic profit per cow had a heritability of 0.29. Heritabilities for eight muscularity traits ranged from 0.16 to 0.23, and for the seven body size traits between 0.21 and 0.30. The conformation trait final score can be used as an early predictor of profitability. The sale price of the animal and differences in the revenue and costs of offspring due to muscularity should be included in a future profit function.

Evaluación de alteraciones hemorreológicas en pacientes hipertensos / Hemorheological alterations in hypertensive patients

El objetivo de este trabajo fue investigar el perfil de viscosidad sanguínea y evaluar la influencia de factores plasmáticos ( fibrinógeno) y celulares ( agregación eritrocitaria ) en un grupo de pacientes hipertensos comparados con un grupo de paciente normotensos. Se trabajó con sangre anticoagulada de pacientes hipertensos no diabéticos (n=3) e indivíduos sanos (n=40). La viscosidad plasmática y de sangre entera se determinaron con un viscosímetro cono-plato. La agregación eritrocitaria se estudió por observación microscopia de los agregados y cuantificación a través de un parâmetro de forma denominado ASP ( Aggregation Shape Parameter), definido como la relación de área proyectada respecto al perímetro. El fibrinógeno se determino con un coagulómetro por el método de Clauss. Los valores de viscosidad de sangre entera resultaron significativamente aumentados en los pacientes hipertensos respecto de los normales para todas las velicidades estudiadas. Los valores de viscosidad plasmática solo presentaron diferencia significativas a bajas velocidades de corte (1.15 a 11.56 seg •1) . Los pacientes hipertensos presentaron agregados amorfos e irregulares, lo que se refleja en los valores alterados de ASP, significativamente mayores (p<0.001) en paciente hipertensos (0.69± 0.11) respecto de los indivíduos normales ( 0.25± 0.12). Los valores de fibrinógeno resultaron ligeramente superiores en los pacientes hipertensos respecto del grupo control (p< 0.01). Numerosos parámetros hemorreológicos juegan un papel importante en la patogénesis de la hipertensión. Entre estos factores hemorreológicos, valores parâmetros podrían estar en la hipertensión ( hematrocito, fibrinógeno plasmático, deformabilidad y agragación eritrocitaria , viscosidad sanguínea y plasmática). En este trabajo, se pudo demostrar anormalidades en la agregación eritrocitaria, detectada por los valores de ASP que podría estar involucrado en las complicaciones vasculares de la hipertensión.

Evaluación de alteraciones hemorreológicas en pacientes hipertensos / Hemorheological alterations in hypertensive patients

El objetivo de este trabajo fue investigar el perfil de viscosidad sanguínea y evaluar la influencia de factores plasmáticos ( fibrinógeno) y celulares ( agregación eritrocitaria ) en un grupo de pacientes hipertensos comparados con un grupo de paciente normotensos. Se trabajó con sangre anticoagulada de pacientes hipertensos no diabéticos (n=3) e indivíduos sanos (n=40). La viscosidad plasmática y de sangre entera se determinaron con un viscosímetro cono-plato. La agregación eritrocitaria se estudió por observación microscopia de los agregados y cuantificación a través de un parÔmetro de forma denominado ASP ( Aggregation Shape Parameter), definido como la relación de área proyectada respecto al perímetro. El fibrinógeno se determino con un coagulómetro por el método de Clauss. Los valores de viscosidad de sangre entera resultaron significativamente aumentados en los pacientes hipertensos respecto de los normales para todas las velicidades estudiadas. Los valores de viscosidad plasmática solo presentaron diferencia significativas a bajas velocidades de corte (1.15 a 11.56 seg ò1) . Los pacientes hipertensos presentaron agregados amorfos e irregulares, lo que se refleja en los valores alterados de ASP, significativamente mayores (p<0.001) en paciente hipertensos (0.69± 0.11) respecto de los indivíduos normales ( 0.25± 0.12). Los valores de fibrinógeno resultaron ligeramente superiores en los pacientes hipertensos respecto del grupo control (p< 0.01). Numerosos parámetros hemorreológicos juegan un papel importante en la patogénesis de la hipertensión. Entre estos factores hemorreológicos, valores parÔmetros podrían estar en la hipertensión ( hematrocito, fibrinógeno plasmático, deformabilidad y agragación eritrocitaria , viscosidad sanguínea y plasmática). En este trabajo, se pudo demostrar anormalidades en la agregación eritrocitaria, detectada por los valores de ASP que podría estar involucrado en las complicaciones vasculares de la hipertensión. (AU)

Phenotypic relationships between longevity, type traits, and production in Chianina beef cattle.

Longevity is an increasingly important trait in beef cattle. Increased longevity decreases costs for the farmer and increases revenue. The objective of this research was to investigate the phenotypic relationship between type traits and longevity in Chianina beef cattle, and the relationship between production and longevity, to analyze the effect of voluntary culling. Data included records on reproductive, productive, and type traits provided by the National Association of Italian Beef Cattle Breeders from 6,395 Chianina cows. The average length of productive life was 1,829 d. The herd-year had a strong effect on the risk of culling. The effects of 22 type traits were analyzed. All the muscularity traits analyzed were highly significant (P < 0.01) and as a group had the largest effect on longevity, followed by dimension, refinement, and leg traits. Cows that calved before 35 mo of age had a lower probability of being culled than cows calving after 35 mo of age. Variation in herd size had a strong effect on risk ratio, with lower risk for intermediate classes. Cows with approximately one calf per year remained in the herd longer than did cows with fewer calves. Straight-legged animals had a 59% greater probability of being replaced than cows with a moderate angle to the hock, whereas sickle-legged animals had only a 3% higher probability of being culled than average cows. Udder conformation had no effect on longevity. In summary, results of this study indicate that herd-year effects and muscularity traits were the most important factors for longevity for Chianina cows among the factors studied.

MECP2 gene mutation analysis in the British and Italian Rett Syndrome patients: hot spot map of the most recurrent mutations and bioinformatic analysis of a new MECP2 conserved region.

Rett syndrome (RTT) is an X-linked dominant neurological disorder, which appears to be the most common genetic cause of profound combined intellectual and physical disability in Caucasian females. This syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of unknown target genes. We report a detailed mutational analysis of a large cohort of RTT patients from the UK and Italy. This study has permitted us to produce a hot spot map of the mutations identified. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, conserved among brain-specific regulatory factors.

Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.

X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with almost five distinct loci on the X chromosome. So far, only two XLRP genes have been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and 10% of the XLRP patients. Clinically there is no clearly significative difference between RP3 and RP2 phenotypes. In the attempt to assess the degree of involvement of the RP2 gene, we performed a complete mutation analysis in a cohort of patients and we identified five novel mutations in five different XLRP families. These mutations include three missense mutations, a splice site mutation, and a single base insertion, which, because of frameshift, anticipates a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a founder effect. Our mutation analysis confirms the percentage of RP2 mutations detected so far in populations of different ethnic origin. In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putative functional domains, and that some novel mutations identify RP2 amino acid residues which are evolutionary conserved, hence possibly crucial to the RP2 function.

Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain.

This article describes the discovery of a novel SNARE domain that might be involved in the regulation of membrane fusion. This domain is shared by a novel family of VAMPs called long VAMPs or longins. Members of this family are more conserved among eukaryotes than are classical VAMPs, possibly because of their underlying basic SNARE function.

Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females.

Rett syndrome is an X-linked dominant neurological disorder, which appears to be the commonest genetic cause of profound combined intellectual and physical disability in Caucasian females. Recently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed. We review the literature on MECP2 mutations in Rett syndrome. This analysis has permitted us to produce a map of the recurrent mutations identified in this and previous studies. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, which is conserved among brain-specific regulatory factors.

Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use.

The biocompatibility of two cyanoacrylate surgical glues (Glubran and Glubran 2), supplied by General Enterprise Marketing, Viareggio, Lucca, Italy, was tested through cytotoxicity and blood compatibility tests and the evaluation of antimicrobial activity. Cytotoxicity and blood compatibility tests were performed on the polymerized glues. Using the neutral red uptake test, the extracts from Glubran and Glubran 2 after polymerization were non-toxic to L929 cells only when diluted 1: 10 with culture medium. Glubran and Glubran 2 induced a significant decrease of activated partial thromboplastin time (APTT), which is favourable with regard to the desired haemostasis. The APTT shortening determines a haemostatic effect and therefore contribute to the tissue adhesion induced by the glues. Otherwise, no significant variation of prothrombin activity, fibrinogen, platelet number, total and differential leukocyte count was induced by the glues, which, in addition, did not show haemolytic effect. There was no difference between Glubran and Glubran 2 regarding haemocompatibility. The antimicrobial ability of the unpolymerized glues was tested onto Bacillus subtilis var. niger for 3 weeks: neither Glubran nor Glubran 2 were found effective in this respect. In conclusion, we can assume that cytotoxicity was severe with the undiluted glues, but was acceptable when glues were diluted. On the contrary, blood compatibility was acceptable for the intended use of the glues. No difference was found between Glubran and Glubran 2 after polymerization.

Modulation of pro- and anti-apoptotic genes in lymphocytes exposed to bone cements.

The ability of bone cements to modify the apoptotic program in activated immune cells and the mechanisms by which they act were evaluated. Mononuclear cells were collected from healthy individuals, cultured for 4 and 24 h with phytohemoagglutinina-P and cement extracts and then tested to assess: (a) cell viability; (b) early apoptotic events, by Annexin V/propidium iodide staining; and (c) the expression of pro- (p53, c-myc, ICE) and anti-apoptotic (bcl-2) genes. After 4 h three cements were able to increase significantly the percentage of apoptotic cells, while after 24 h no differences were found. The proportion of dead cells was not significantly changed at either culture time. The simultaneous expression of both pro-apoptotic (ICE, c-myc, p53) and antiapoptotic genes (bcl-2) was investigated only with regard to the materials which induced significant changes in apoptosis: two cements induced the p53 expression, while the third down-regulated bcl-2. As apoptosis regulates the balance of immune response, the authors recommend that the interaction between materials and immune cells should be assessed, so that the use of pro-apoptotic materials may be avoided in patients with immune defects.

The long styloid process syndrome or Eagle's syndrome.

Eleven cases of Eagle's syndrome or long styloid process syndrome are presented. It is a rare entity, which is not commonly suspected in clinical practice. Symptoms were dull and persistent pharyngeal pain, dysphagia, and facial pain. In addition to careful clinical examination, the use of plain radiographs, orthopantomograms or CT scan has allowed accurate preoperative diagnosis of this syndrome. Surgical treatment has positively resolved the symptoms in these cases. The International literature is discussed regarding anatomy, symptoms and treatment of the long styloid process syndrome.

Expression of the CD69 activation antigen on lymphocytes of patients with hip prosthesis.

The aim of the study was to evaluate the sensitization to metals in patients with Co-Cr hip prosthesis. Peripheral blood mononuclear cells (PBMC) were collected from 14 healthy donors and three groups of patients: 10 candidates for primary total joint replacements, 11 patients with well-fixed implant and 13 patients with aseptic loosening of the hip prosthesis. PBMCs were cultured with the metal ions employed for implant manufacturing and the expression of CD69 activation antigen on CD3/T lymphocytes was detected by flow cytometry. Chromium extract increased significantly the expression of CD3/CD69 phenotype in patients with loosening of hip prosthesis. The chromium-induced 'activation index' was higher in patients with loosening of hip prosthesis than in healthy donors and in pre-implant patients. The cobalt-stimulated PBMC of patients with either well-fixed or loosened prosthesis had an 'activation index' significantly higher than healthy donors. The activation index values were used to graduate the PBMC-response as 'normal' (> or = 0.9 and < 2), 'low' (< 0.9) and 'high' (> or = 2): an high-activation index was observed only in chromium-exposed PBMC of patients with prosthesis. Our data show that chromium released from orthopedic implants could be responsible for the lymphocyte sensitization and flow cytometry is an easy and reliable method for monitoring the hypersensitivity state in patients with metal prostheses. Activated lymphocytes in the peri-implant tissue are likely to elicit a localized immune response and contribute to maintain the inflammatory process evolving in the implant failure.

In vitro cytokine production by mononuclear cells exposed to bone cement extracts.

The authors evaluated the ability of bone cement to modify the profile of pro-inflammatory cytokines secreted by the immune cells. Peripheral blood mononuclear cells (PBMC) collected from healthy individuals were cultured with cement extracts and tested to assess the release of IL-1beta, TNFalpha, GM-CSF and IL-6 in both unstimulated and PHA-stimulated PBMC. The cytokine release of unstimulated PBMC was very poor, and in particular the IL-1beta was undetectable: the addition of cement extract increased both TNFalpha and GM-CSF release and decreased IL-6, sometimes significantly. The most recurrent observation in PHA-stimulated PBMCs exposed to bone cement extract was the increase in both IL-1beta and IL-6 release, while both the mean concentration and the index of release of TNFalpha and GM-CSF were changeable. In conclusion our results showed that leachable components of some bone cements can induce in vitro the release of pro-inflammatory cytokines which are known to be involved in the bone resorption associated with aseptic loosening of hip prostheses. These findings allowed us to identify materials endowed with the highest inflammatory power.

Identification and characterization of an 18-kilodalton, VAMP-like protein in suspension-cultured carrot cells.

Polyclonal antibodies raised against rat vesicle associated membrane protein-2 (VAMP-2) recognized, in carrot (Daucus carota) microsomes, two major polypeptides of 18 and 30 kD, respectively. A biochemical separation of intracellular membranes by a sucrose density gradient co-localized the two polypeptides as resident in light, dense microsomes, corresponding to the endoplasmic reticulum-enriched fractions. Purification of coated vesicles allowed us to distinguish the subcellular location of the 18-kD polypeptide from that of 30 kD. The 18-kD polypeptide is present in the non-clathrin-coated vesicle peak. Like other VAMPs, the carrot 18-kD polypeptide is proteolyzed by tetanus toxin after separation of coatomers. Amino acid sequence analysis of peptides obtained by digestion of the 18-kD carrot polypeptide with the endoproteinase Asp-N confirms it to be a member of the VAMP family, as is suggested by its molecular weight, vesicular localization, and toxin-induced cleavage.