Osteoglycin, a novel coordinator of bone and glucose homeostasis.

OBJECTIVE: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. METHODS: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. RESULTS: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. CONCLUSIONS: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

Central RANK signalling in NPY neurons alters bone mass in male mice.

RANKL signalling known to be important for the control of bone mass, has recently also been implicated in the brain to control thermoregulation, however, it is not known which neuronal pathways are involved and whether other aspects of energy homeostasis are also affected. Here we show that selective deletion of RANK from NPY neurons down-regulated NPY mRNA expression in the hypothalamus. While comprehensive phenotyping of germline-induced NPY neuron specific RANK deficient mice revealed no significant changes in physical or metabolic parameters, adult onset deletion of RANK from NPY neurons led to a significant increase in fat mass and a decrease in whole body bone mineral content and bone mineral density. Intriguingly, when these conditional knockout mice were placed on a high fat diet, body weight and fat mass did not differ to control mice. However, they were able to significantly increase their bone mass to match their increased body weight, an ability that was lacking in control mice. Taken together, results from this study demonstrate that RANK signalling in NPY neurons is involved in modulating NPY levels and through that matching bone mass to body weight.

Comparison of gene expression in post-smolt Atlantic salmon challenged by LF-89-like and EM-90-like Piscirickettsia salmonis isolates reveals differences in the immune response associated with pathogenicity.

Piscirickettsiosis is the main bacterial disease affecting the Chilean salmon farming industry and is responsible for high economic losses. The aim of this study was to describe and comparatively quantify the immune response of post-smolt Atlantic salmon infected by cohabitation with fish bearing LF-89-like and EM-90-like Piscirickettsia salmonis. The expression of 17 genes related to the immune response was studied in head kidney from cohabitant fish by RT-qPCR. Our results at the transcriptomic level suggest that P. salmonis is able to manipulate the kinetics of cytokine production in a way that might constitute a virulence mechanism that promotes intracellular bacterial replication in cells of Atlantic salmon. This strategy involves the creation of an ideal environment for the microorganism based on induction of the inflammatory and IFN-mediated response, modulation of Th1 polarization, reduced antigen processing and presentation, modulation of the evasion of the immune response mediated by CD8+ T cells and promotion of the CD4+ T-cell response during the late stage of infection as a mechanism to escape host defences. This response was significantly exacerbated in fish infected by PS-EM-90 compared with fish infected by PS-LF-89, a finding that is probably associated with the higher pathogenicity of PS-EM-90.

Comparative pathogenesis of piscirickettsiosis in Atlantic salmon (Salmo salar L.) post-smolt experimentally challenged with LF-89-like and EM-90-like Piscirickettsia salmonis isolates.

Piscirickettsiosis (SRS) is the most prevalent bacterial disease in Chilean salmon aquaculture and is responsible for high economic losses. The aim of this study was to comparatively characterize the pathogenesis of SRS in post-smolt Atlantic salmon during the early and late stages of infection with Piscirickettsia salmonis LF-89-like (PS-LF-89) and EM-90-like (PS-EM-90) using a cohabitation challenge. The pathogenesis of cohabitant fish infected with the two isolates was relatively different due to cohabitant fish infected with PS-EM-90 showing higher cumulative mortality and shorter time until death compared with PS-LF-89 fish. PS-LF-89 caused an SRS infection characterized by kidney and liver lesions, whereas PS-EM-90 caused systemic and haemorrhagic disease characterized by kidney, liver, heart, brain, skeletal muscle and intestine lesions. Decreased serum concentration of total proteins and albumin as well as increased serum ALT, AST and creatinine levels in fish infected with both isolates confirmed that changes in liver and kidney function occurred during infection. Tissue damage, expressed as an SRS histoscore, showed a strong positive correlation with the bacterial load expressed as abundance of P. salmonis 16S rRNA transcripts in the livers and kidneys of fish affected with either isolate, but the correlation was significantly higher in fish infected with PS-EM-90. The results contribute to improving the understanding of the bacteria-host interaction.

[Obstetric hysterectomy in patients with accreta, increta and percreta placentae: comparison of two surgical techniques]. / Histerectomía obstétrica en pacientes con placenta acreta, increta y percreta: comparación de dos técnicas quirúrgicas.

OBJECTIVE: To analyze the maternal-fetal surgical complications techniques utilizing two obstetric hysterectomy in patients with placenta accreta, increta or percreta, in the Hospital General de Occidente, Jalisco, Mexico during the period 2011 to 2014. MATERIAL AND METHODS: observational, descriptive, cross-sectional study, analyzing maternal and fetal complications in all patients diagnosed with placenta accreta, increta or percreta, intervened with two surgical techniques obstetric hysterectomy, during the period January 2011 to December 2014, using clinical records to identify the study variables. The data were analyzed on Epi-Info 7 calculating frequencies, percentages, measures of central tendency and dispersion, also resorting to the use of a hypothesis test for mean difference bleeding. RESULTS: There were 71 obstetric hysterectomies, 47.88% were identified by placenta accreta, increta or percreta, of which 47.05% were operated with modified technique (group 1) and 52.95% with the conventional technique (group 2). The mean ages of the groups were 31.56 in group 1 and 29.44 in group 2. Statistically the bleeding with the modified surgical technique it is less than the bleeding conventional technique. CONCLUSIONS: The results serves two main purposes: to save the life of the patient and cause the least amount of side morbidity are placental problems, both the mother and the newborn, highlighting minor bleeding from a technique to another.

Anatomical Variations of the Thoracic Duct: A Preliminary Report in Adult and Fetal Specimens.

The study aim is to evaluate anatomical variations of the thoracic duct using a specialized sequential injection procedure. The different types, frequencies, and anatomical topography were recorded and evaluated using 12 adult and 16 fetus specimens. By employing a perfusion pump device, cadavers were sequentially perfused with acrylic colored latex first through the internal marginal vein, then the thoracic duct at the interazygous-aortic recess, and finally through the posterior tibial artery. After perfusion, thoracic ducts were identified, partially dissected, and cadavers fixed by soaking in an aqueous solution of 5% formalin (v/v). Finally, further dissection and detailed photography were performed. Plexus shapes at different levels were clearly evident in 80% of the adult specimens. Whereas the presence of the cisterna chyli was detected in 100% of fetuses as an ampule dilatation at the beginning of the thoracic duct, in only one adult specimen was a dilatation found at the lumbar lymphatic trunk level. Functionally it is not known whether these modified anatomical features (plexus shapes) have served to compensate (as a derivative pathway) for lymphatic hypertension in life as a reflection of lymphatic system challenges and subsequent growth in the adult specimens.

Establishment and characterization of a new cell line (SSP-9) derived from Atlantic salmon Salmo salar that expresses type I ifn.

In the present work, the establishment and biological characterization of a new cell line, SSP-9, derived from the pronephros of the Atlantic salmon Salmo salar, are reported. These cells grew well in Leibovitz's (L15) medium supplemented with 10% foetal calf serum at temperatures from 15 to 25° C, and they have been sub-cultured over 100 passages to produce a continuous cell line with an epithelial-like morphology. The SSP-9 cells attached and spread efficiently at different plating densities, retaining 80% of cell viability after storage in liquid nitrogen. When karyotyped, the cells had 40-52 chromosomes, with a modal number of 48. Viral susceptibility tests showed that SSP-9 cells were susceptible to infectious pancreatic necrosis virus and infectious haematopoietic necrosis virus, producing infectious virus and regular cytopathic effects. Moreover, these cells could be stimulated by poly I:C, showing significant up-regulation in the expression of the genes that regulate immune responses, such as ifn and mx-1. SSP-9 cells constitutively express genes characteristic of macrophages, such as major histocompatibility complex (mhc-II) and interleukin 12b (il-12b), and flow cytometry assays confirmed that SSP-9 cells can be permanently transfected with plasmids expressing a reporter gene. Accordingly, this new cell line is apparently suitable for transgenic manipulation, and to study host cell-virus interactions and immune processes.

Neuropeptide y attenuates stress-induced bone loss through suppression of noradrenaline circuits.

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress-induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress-induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6-week restraint, or cold-stress protocol, Npy-null mice exhibit three-fold greater bone loss compared to wild-type mice, owing to suppression of osteoblast activity. This stress-protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin-releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy-null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy-null mice blocks the increase in circulating noradrenaline and the stress-induced bone loss. Thus, NPY protects against excessive stress-induced bone loss, through Y2 receptor-mediated modulation of central and peripheral noradrenergic neurons.

Piscirickettsiosis and Piscirickettsia salmonis in fish: a review.

The bacterium Piscirickettsia salmonis is the aetiological agent of piscirickettsiosis a severe disease that has caused major economic losses in the aquaculture industry since its appearance in 1989. Recent reports of P. salmonis or P. salmonis-like organisms in new fish hosts and geographical regions have increased interest in the bacterium. Because this gram-negative bacterium is still poorly understood, many relevant aspects of its life cycle, virulence and pathogenesis must be investigated before prophylactic procedures can be properly designed. The development of effective control strategies for the disease has been limited due to a lack of knowledge about the biology, intracellular growth, transmission and virulence of the organism. Piscirickettsiosis has been difficult to control; the failure of antibiotic treatment is common, and currently used vaccines show variable long-term efficacy. This review summarizes the biology and characteristics of the bacterium, including its virulence; the infective strategy of P. salmonis for survival and evasion of the host immune response; the host immune response to invasion by this pathogen; and newly described features of the pathology, pathogenesis, epidemiology and transmission. Current approaches to the prevention of and treatment for piscirickettsiosis are discussed.

Spirotetramat induce cambios histológicos y bioquímicos en rata Wistar / Spirotetramat induces histological and biochemical changes in Wistar rats

Spirotetramat, comercialmente conocido como Movento®, es derivado del ácido tetrámico, empleado en el cultivo de la vid y de algunos vegetales para el control de parásitos chupadores. Los estudios toxicológicos in vivo solo publican una descripción general de su metabolismo. El objetivo de este estudio fue conocer los cambios en el comportamiento, en indicadores bioquímicos séricos e histológicos en ratas Wistar macho. Se realizó los siguientes tratamientos: a) intoxicación aguda con Spirotetramat (BY108330, 15.3%) vía oral con 1⁄4 DL50 (625 mg kg-1) y 1⁄2 DL50 (1250 mg kg-1), y b) control. Se obtuvieron muestras de sangre mediante punción cardíaca los días 1, 3 y 7; las muestras se evaluaron por cambios en indicadores bioquímicos (triglicéridos, colesterol, albúmina, proteína total, actividad de transaminasas, urea y creatinina), y cambios histológicos en hígado, riñón y páncreas. Se presentó la muerte en el 35% de los animales tratados. Se observaron signos de toxicidad como: salivación, ataxia, convulsiones, sangrado nasal y diarrea. El peso corporal y el peso relativo del hígado en promedio fueron constantes, sin diferencias entre tratamientos, ni entre días. El perfil lipídico y las transaminasas presentaron una tendencia al incremento en relación al control. En la evaluación histológica los hepatocitos mostraron degeneración balonoide en el 25% (8 de 32) y colestasis en el 72% (23 de 32) de las ratas intoxicadas, sin embargo en bazo y riñón no se observaron cambios visibles en relación al control (AU)

Spirotetramat, derived from tetramic acid, and commercially known as Movento®, is applied in grapevine orchards and other vegetable for the control of sucking pests. Published in vivo toxicological studies report only a general description of its metabolism. The objective of this study was to detect changes in the behavior, in blood biochemical markers, and in histological liver cells on male Wistar rats treated with spirotetramat. The following treatments were applied: a) acute poisoning with spirotetramat (BY108330, 15.3%) oral route with 1⁄4 DL50 (625 mg kg- 1) and 1⁄2 DL50 (1250 mg kg-1), and b) control. Blood samples were obtained by heart punction on days 1, 3 and 7; the samples were evaluated for changes of biochemical indicators (triglycerides, cholesterol, albumin, total protein, transaminase activity, urea and creatinine), and by histological changes in liver, kidney and pancreas. Death occurred in 35% of the treated animals. Some signs of toxicity were observed: nasal running, diarrhea, salivation, ataxia, convulsions, and bleeding. The average body weight and the liver relative weight were stable during the experiment, without differences between treatments, nor between days. The lipid profile and transaminases showed a clear tendency to increase in relation to the control. In the histological evaluation the hepatocytes showed balloonoide degeneration in 25% (8 of 32) and cholestasis in 72% (23 of 32) of the exposed rats; however, there were not visible changes in spleen and kidney in relation to the control (AU)

Nephrotic syndrome and AA amyloidosis revealing adult-onset cryopyrin-associated periodic syndrome.

Cryopyrin-associated periodic syndrome (CAPS) is due to gain-of-function mutations in the cryopyrin gene, which determines an overactive inflammatory response. AA amyloidosis is a complication of this syndrome. A 53-year-old man was referred to us because of lower limb edema. Past history: at the age of 20, he complained of arthralgia/arthritis and bilateral hypoacusis. At the age of 35, he presented posterior uveitis, several episodes of conjunctivitis, and progressive loss of visual acuity. Laboratory tests disclosed nephrotic syndrome, and renal biopsy showed AA amyloidosis. He was given anakinra with improvement of arthritis. A genetic study revealed the p.D303N mutation in the cryopyrin gene, and he was diagnosed as having AA amyloidosis due to CAPS. Twenty-one months after starting anakinra, the arthritis has disappeared, although nephrotic-range proteinuria persisted. It is important to be aware of cryopyrin-associated periodic syndrome because it can cause irreversible complications, and there is effective therapy.

Tocilizumab treatment for nephrotic syndrome due to amyloidosis in Behcet's disease.

Renal involvement is an unusual but significant Behcet´s disease (BD) complication and AA amyloidosis appears to be the most common etiology. IL-6 is a pro-inflammatory cytokine with an important role in AA amyloidosis development. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that has emerged as an effective and specific treatment in AA amyloidosis secondary to chronic inflammatory disorders. We report on a patient diagnosed with BD who developed nephrotic syndrome caused by renal AA amyloidosis with an excellent response to TCZ therapy.

Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice.

BACKGROUND: Estrogen deficiency increases body weight or total and central adiposity and decreases energy expenditure. Hypothalamic neuropeptide Y (NPY) expression is altered by estrogen deficiency in rodents, but the long-term consequences on energy homeostasis are unknown. OBJECTIVE: To investigate the role of NPY in the changes in energy expenditure and physical activity, as well as the associated changes in body weight and composition in response to short-term and long-term estrogen deficiency. DESIGN: Sham and ovariectomy (OVX) operations were performed at 8 weeks of age in wild-type (WT) and NPY(-/-) mice. Energy expenditure, physical activity, body composition and weight, as well as food intake were measured at 10-18 days (short-term) and 46-54 days (long-term) after OVX. RESULTS: OVX influences energy homeostasis differently at early compared with later time-points. At the early but not the late time point, OVX in WT mice reduced oxygen consumption and energy expenditure and tended to reduce resting metabolic rate. Interestingly, these effects of short-term estrogen deficiency were ablated by NPY deletion, with NPY(-/-) mice exhibiting significant increases in energy expenditure and resting metabolic rate. In addition to these hypermetabolic effects, OVX NPY(-/-) mice exhibited significantly lower body weight and whole-body fat mass relative to OVX WT controls at the short-term but not the long-term time point. Food intake and physical activity were unaltered by OVX, but NPY(-/-) mice exhibited significant reductions in these parameters relative to WT. CONCLUSION: The effects of estrogen deficiency to reduce energy metabolism are transient, and NPY is critical to this effect as well as the early OVX-induced obesity.

Broth medium for the successful culture of the fish pathogen Piscirickettsia salmonis .

Piscirickettsiosis or salmonid rickettsial septicaemia (SRS) caused by Piscirickettsia salmonis constitutes one of the main problems in farmed salmonid and marine fishes. Since the first reports of the disease, it has been successfully isolated and maintained in eukaryotic cell--culture systems, but these systems are time-consuming, the media are costly, and eliminating heavily contaminated host cell debris is difficult. In this report, we describe a marine-based broth supplemented with L-cysteine, named AUSTRAL-SRS broth, that facilitates superior growth of P. salmonis strains. Strains reached an optical density of approximately 1.8 when absorbance was measured at 600 nm after 6 d incubation at 18°C. Several passages (n = 6) did not alter the culture kinetics. We report for the first time the purification of DNA, lipopolysaccharide (LPS) and whole membrane protein obtained from P. salmonis grown in this liquid medium, and thus provide a suitable platform to simplify the preparation of P. salmonis cells for genetic and serological studies. Moreover, the results of the cytopathic effect test showed that P. salmonis grown in AUSTRAL-SRS broth maintained their virulence properties, inducing apoptosis after 3 d. This makes the medium a good candidate for the successful growth of P. salmonis and an excellent basis for the development of low cost vaccines.

NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.

AIMS: Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. METHODS: To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. RESULTS: PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. CONCLUSIONS: These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis.

[Non compaction cardiomyopathy: a series of 15 cases]. / Miocardiopatía no compactada: una serie de 15 casos.

BACKGROUND: Non compaction cardiomyopathy is a rare disorder caused by the arrest of myocardial compaction during embryogenesis, leading to a non compacted endocardial layer with marked hypertrabeculation and deep recesses. AIM: To report the clinical and echocardiographic characteristics of a series of 15 adult patients with non-compaction cardiomyopathy. PATIENTS AND METHODS: We included a total of 15 patients aged 52 ± 17 years (40% males) diagnosed at our echocardiography laboratory between January 2001 and July 2010. RESULTS: The form of presentation was heart failure in 53% of subjects, syncope in 20%o, ventricular arrhythmias in 13%o and stroke in 7%>. Left ventricular end-diastolic diameter was 66 ± 11 mm and estimated ejection fraction was 27 ± 10%>. Apical and/or mid-ventricular segments of the left ventricle were involved in all the cases. Pulmonary hypertension was present in 40%o. The average follow-up was 19 months and no patient died during this period. Sixty seven percent of the patients had manifestations of heart failure, 27%o presented sustained ventricular arrhythmias and 20%> had atrial fibrillation or flutter, whereas 13%o had cerebral embolic events. An automated internal cardioverter defibrillator was implanted in 47%o of patients. CONCLUSIONS: Non-compaction cardiomyopathy is associated with high cardiovascular morbidity. The diagnosis is made in advanced stages of the disease, with significant dilation and ventricular dysfunction.

Hepatotoxicidad tras tratamiento con ciclofosfamida en un paciente con vasculitis MPO-ANCA / Hepatotoxicity following cyclophosphamide treatment in a patient with MPO-ANCA vasculitis

No disponible

Miocardiopatía no compactada: una serie de 15 casos / Non compaction cardiomyopathy: a series of 15 cases

Background: Non compaction cardiomyopathy is a rare disorder caused by the arrest of myocardial compaction during embryogenesis, leading to a non compacted endocardial layer with marked hypertrabeculation and deep recesses. Aim: To report the clinical and echocardiographic characteristics of a series of 15 adult patients with non-compaction cardiomyopathy. Patients and Methods: We included a total of 15 patients aged 52 ± 17 years (40 percent males) diagnosed at our echocardiography laboratory between January 2001 and July 2010. Results: Theform of presentation was heart failure in 53 percent of subjects, syncope in 20 percento, ventricular arrhythmias in 13 percento and stroke in 7 percent>. Left ventricular end-diastolic diameter was 66 ±11 mm and estimated ejection fraction was 27 ± 10 percent>. Apical and/or mid-ventricular segments of the left ventricle were involved in all the cases. Pulmonary hypertension was present in 40 percento. The average follow-up was 19 months and no patient died during this period. Sixty seven percent ofthe patients had manifestations of heart failure, 27 percento presented sustained ventricular arrhythmias and 20 percent> had atrial fibrillation orflutter, whereas 13 percento had cerebral embolic events. An automated internal cardioverter defibrillator was implanted in 47 percento of patients. Conclusions: Non-compaction cardiomyopathy is associated with high cardiovascular morbidity. The diagnosis is made in advanced stages of the disease, with significant dilation and ventricular dysfunction.