Small fragments of hyaluronan are increased in individuals with obesity and contribute to low-grade inflammation through TLR-mediated activation of innate immune cells.

BACKGROUND AND AIM: Extracellular matrix (ECM) components released during excessive fat mass expansion are considered potential endogenous danger/alarm signals contributing to innate immune system activation. The aim of the current study was to specifically measure plasma levels of low molecular weight (LMW) hyaluronan (HA) and to evaluate its role as pro-inflammatory damage-associated molecular pattern (DAMP) on leukocyte response in the context of human obesity. SUBJECTS AND METHODS: Participants were selected according to their body mass index (BMI, kg/m2) as non-obese (BMI < 29.9, n = 18) and obese (BMI > 29.9, n = 33). Plasma samples were size-dependent fractionated using ion-exchange chromatography to specifically obtain LMW HA fractions that were subsequently quantified by ELISA. Cell incubation experiments with synthetic HA molecules were performed on freshly Ficoll-isolated neutrophils (PMN) and peripheral blood monocytes (PBMC). Leukocyte and adipose tissue gene expression was assessed by real-time PCR and NF-κB activation by western blot. Plasma cytokine levels were measured by fluorescent bead-based (Luminex) immunoassay. RESULTS: We observed a statistically significant increase in the circulating levels of HA fragments of LMW in individuals with obesity which were consistent with significant up-regulated expression of the LMW HA synthesizing enzyme hyaluronan synthase-1 (HAS-1) in obese adipose tissue. Gene expression assessment of HA receptors revealed up-regulated levels for TLR2 in both obese PMN and PBMC. Synthetic HA molecules of different sizes were tested on leukocytes from healthy donors. LMW HA fragments (15-40 kDa) and not those from intermediate molecular sizes (75-350 kDa) induced a significant up-regulation of the expression of major pro-inflammatory cytokines such as IL-1ß, MCP-1 and IL-8 in PBMC. Importantly, LMW HA was able to induce the phosphorylation of IKK α/ß complex supporting its pro-inflammatory role through NF-κB activation. CONCLUSION: Circulating LMW HA molecules are elevated in obesity and may play an important role in triggering low-grade inflammation and the development of metabolic complications.

Translational evidence of prothrombotic and inflammatory endothelial damage in Cushing syndrome after remission.

OBJECTIVE: Sustained evidence from observational studies indicates that after remission of Cushing syndrome (CS) a cardiovascular risk phenotype persists. Here, we performed a translational study in active CS and CS in remission (RCS) to evaluate the subclinical cardiometabolic burden and to explore the direct pro-inflammatory and prothrombotic potential of their sera on the endothelium in an in vitro translational atherothrombotic cell model. PATIENTS: Cross sectional study. The groups were (n = 9/group): I. RCS; II. Active CS (ACS) and III. Controls (CTR), all matched for age, body mass index, sex, without other hormonal deficits. DESIGN: We evaluated in vivo: cardiometabolic profile; endothelial markers (sVCAM-1, NO); endothelial dysfunction (FMD); intima-media thickness and body composition (DEXA). In vitro endothelial cells (EC) were exposed to sera taken from the different subjects to evaluate inflammatory EC response (tisVCAM) and thrombogenicity of the generated extracellular matrix (ECM): von Willebrand factor (VWF) and platelet reactivity. RESULTS: Three of the 9 RCS subjects were on glucocorticoid replacement therapy (GC-RT). Patients on GC-RT had a shorter period of time in stable remission. In vivo analysis ACS showed typically metabolic features, while cardiometabolic markers reached statistical significance for RCS only for Hs-CRP (P < .01). In vitro:EC exposed to ACS and RCS sera displayed increased tisVCAM-1 (P < .01 for ACS and P < .05 for RCS vs CTR), VWF (P < .01 for ACS and P < .05 for RCS vs CTR) and platelet adhesion on ECM (P < .01 for ACC and P < .05 for RCS vs CTR). No statistically significant differences were observed between GC-RT RSC and RCS without GC-RT. CONCLUSIONS: The sera of premenopausal women with CS in remission, without atherothrombotic disease, contain circulatory endothelial deleterious factors with a direct thrombogenic and pro-inflammatory endothelial effect that could increase cardiovascular risk.

Detection of early seeding of Richter transformation in chronic lymphocytic leukemia.

Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)high-B cell receptor (BCR)low-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.

Non-toxic doses of modified titanium dioxide nanoparticles (m-TiO2NPs) in albino CFW mice.

Modified titanium dioxide (m-TiO2NPs) is a novel photocatalytic nanomaterial. Its level of toxicity was evaluated to be used in photodynamic treatment for cervical cancer. In the toxicity studies (Irwin test, acute and repeated doses (10 days)), female albino Swiss Webster (CFW) mice, 28 days old were used; the m-TiO2NPs was administered in single 300, 600 and 5,000 mg/kg of body weight (b.w) doses injected in the peritoneal zone. No adverse events or mortality were produced. Daily intraperitoneal doses of 300 and 600 mg/kg b.w every 24 h for 10 days did not produce adverse effects or mortality. There were no abnormal clinical signs or behavioral changes (neurological or physiological) in any of the mice. All organs exhibited normal architecture, and histological studies determined that m-TiO2NPs does not produce changes in the cells or tissues. Based on the test results, it is concluded that the m-TiO2NPs has not a toxic effect in doses equal to or less than 5,000 mg/kg b.w.

List of bats register at high altitudes in Río Abiseo National Park

We present a list of bats collected above 2000 meters in Río Abiseo National Park. Sixteen bat species belonging to the Phyllostomidae and Vespertilionidae families were collected during four expeditions between 1987 and 1990. Twelve species were found within expected altitudinal ranges, but four exceeded their previously reported maximum altitudinal ranges. A comparison with other bat lists from other localities at similar altitudes is presented.

Se presenta una lista de murciélagos colectados por encima de los 2000 m en el Parque Nacional Río Abiseo. Dieciséis especies de murciélagos pertenecientes tanto a las familias Phyllostomidae y Vespertilionidae fueron colectadas durante cuatro expediciones realizadas entre 1987 y 1990. Doce especies fueron encontradas dentro de los rangos altitudinales esperados, pero cuatro excedieron su altitud máxima previamente reportada. Se presenta una comparación con otras listas de murciélagos de otras localidades a altitudes similares.

[The seeds of Campsiandra angustifolia (Fabaceae: Caesalpiniodeae) as a reflex of selective pressures on dispersal and establishment]. / La semilla de Campsiandra angustifolia (Fabaceae: Caesalpiniodeae) como un reflejo de las presiones selectivas sobre su dispersión y establecimiento.

We indirectly evaluated the selective pressures on dispersal and establishment of Campsiandra angustifolia, a common water-dispersed tree from the Peruvian Amazon, analyzing the variation in the relationship between the volume occupied by dispersal and establishment structures in a total of 535 seeds from 13 trees located at three different habitats. The seeds differed one order of magnitude in their total volume. However, independently of their size and the location of the maternal tree, the relationship between the volume occupied by dispersal and establishment structures was relatively constant (approximately 1) and showed a normal distribution with low skewness, indicating stabilizing selection. These results suggest that, in the habitats studied, dispersal and establishment processes may have similar importance to C. agustifolia. In species with seeds confined in pods, and therefore strongly space-limited, the relative volume of their seeds occupied by dispersal and establishment structures could be a better measure of the trade-off between these two processes than the variation in seed size.

Transient mesenteric ischemia leads to remodeling of rat mesenteric resistance arteries.

Mesenteric ischemia/reperfusion (I/R) is associated with high rates of morbidity and mortality. We studied the effect of mesenteric I/R on structural and mechanical properties of rat mesenteric resistance artery (MRA) that, once disrupted, might impact the outcome of this devastating clinical condition. Superior mesenteric artery from Wistar-Kyoto rats was occluded (90 min) and reperfused (24 h). The effect of tezosentan, a dual endothelin (ET)-receptor antagonist, was studied in ischemic (IO) and sham-operated (SO) animals. MRA structure and mechanics were assessed by pressure myography. Nuclei distribution, elastin content and organization, collagen I/III and ET-1 expression, ET-1 plasma levels, superoxide anion ([Formula: see text]) production, and mRNA levels of NAD(P)H-oxidase subunits were measured. To assess ET-1 effects on [Formula: see text] production, MRA from non-operated rats were incubated in culture medium with ET-1. Mesenteric I/R increased MRA wall thickness (P < 0.05) and cross-sectional area (P < 0.05) but decreased wall stiffness (P < 0.05). Arterial remodeling was paralleled by enhancement of: (i) collagen I/III expression (P < 0.01), ET-1 expression (P < 0.05), and [Formula: see text] formation (P < 0.01) in the vessel wall; (ii) number of internal elastic lamina (IEL) fenestrae (P < 0.05); and (iii) plasma levels of ET-1 (P < 0.05). Moreover, ET-1 increased [Formula: see text] (P < 0.05) production in cultured MRA. Tezosentan prevented hypertrophic remodeling and collagen I/III deposition, and enhanced [Formula: see text] production, but it did not affect the decreased wall stiffness after mesenteric I/R. These results indicate that 90 min occlusion/24 h reperfusion induces hypertrophic remodeling of MRA linked to ET-1-mediated increase of collagen and [Formula: see text]. Decreased stiffness may be associated with increased number of IEL fenestrae. The resulting MRA remodeling, initially adaptive, might become maladaptive contributing to the pathology and poor outcome of mesenteric I/R, and might be a valuable treatment target for mesenteric I/R.

Escasa presencia y grave amenaza para el “cortarramas peruano”, Phytotoma raimondii

En este artículo presentamos una actualización del estado de conservación del “cortarramas peruano”, indicando su escasa presencia dentro del área de distribución de la especie y sus amenazas. Desde Tumbes hasta Ancash se han identificado solo seis lugares donde existen poblaciones de más de 10 individuos y tres sitios en los que se reproduce. Los resultados indican que en total la población actual sería inferior a 500 individuos. Estos sitios contienen especies de flora representativa del matorral desértico peruano, varias de las cuales están amenazadas. Los sitios son muy pequeños (entre 5 y 150 ha), están muy fragmentados y se encuentran en inminente peligro de destrucción debido a la expansión urbana y agrícola, tala ilegal, sobre pastoreo e introducción de especies vegetales exóticas.

In this article, we present an update on the conservation statuts of the Peruvian Plantcutter. We find little presence of the species within its distribution area we catalog threats to the remaining populations. From Tumbes to Ancash only six sites have been identified with populations of more than 10 individuals and only three sites where the species is known to reproduce. Results indicate that the current total population is less than 500 individuals. These sites where the species is found contain floral species typical of the Peruvian desert scrub, several of which are threatened. Sites are very small (between 5 to 150 ha), highly fragmented and are under immediate threat of destruction due to agriculture, urban expansion, illegal logging, livestock foraging, and the introduction of exotic plant species.

Reproducción y alimentación de Phytotoma raimondii, cortarrama peruana en El Gramadal, Ancash

Se confirma la existencia de un buen hábitat con buena disponibilidad de alimento y de sitios para reproducción de la cortarrama peruana en El Gramadal (Huarmey). Las dos especies más importantes para su alimentación "algarrobo" (Prosopis pallida) y "palo negro" (Grabowskia boerhaviifolia), se encuentran en suficiente cantidad en el lugar. Esta última planta también es crucial para la reproducción, ya que todos los nidos hallados fueron construidos en esta especie. Hasta el momento se han encontrado nueve nidos entre los años 2010 y 2012 entre diciembre y abril: siete nidos activos, 2 el 2010 (abril), 4 el 2011, (marzo y diciembre) y uno el 2012 (enero). También se encontraron dos nidos vacíos el 2011 (marzo y junio), además de volantones e individuos juveniles desde diciembre a junio.

The occurrence of good habitat with suitable food and sites for reproduction for the Peruvian plantcutter at El Gramadal (Huarmey) is confirmed. The two most important species for food "algarrobo" (Prosopis pallida) and "palo negro" (Grabowskia boerhaviifolia) both occur in sufficient amount in this place. The last species is also crucial for the reproduction since all the nests found were in this species. To date 9 nests have been found during 2010 and 2012 and between December and April: seven active nests, 2 in 2010 (April) and 4 in 2011(March and December) and 1 in 2012 (January). In addition, two empty nests were found in 2011 (March and June), and fledglings and juveniles from December to June.

On the density-dependence of seed predation in Dipteryx micrantha, a bat-dispersed rain forest tree.

We studied the effect of seed density on seed predation by following the fate of bat-dispersed Dipteryx micrantha (Leguminosae) seeds deposited under bat feeding roosts. The study was conducted in Cocha Cashu biological station, Amazonian Peru, during the fruiting period of Dipteryx. Predation of Dipteryx seeds in the area is mainly by large to medium-sized rodents. Seed deposits beneath bat feeding roosts were monitored for a 13-week period in an 18-ha study area. A total of 210 seed deposits were found, and on average, seed predators encountered 22% of them during any one week. About one-third of the seed deposits escaped predation, and those deposits that had relatively few seeds were more likely to go unnoticed by rodents than were deposits with many seeds. The mean seed destruction rate was 8% per week; deposits with many seeds tended to lose a smaller proportion of their seeds to seed predators than did deposits with few seeds. Regression tests for the weekly data showed that, at the beginning of the observation period, seed predation was not density-dependent. Later, when the total seed crop beneath roosts was high, the number of seeds predated per deposit was positively density-dependent, while the proportion of seeds predated was negatively density-dependent, indicating predator satiation. Seed deposits that had been visited by seed predators once had a higher probability of being revisited the week after, especially if they contained many seeds when first encountered. This indicates that the foraging behavior of rodents may be affected by their remembering the location of seed-rich patches.

Blunt abdominal injury in the pregnant patient: detection with US.

PURPOSE: To determine the accuracy of ultrasonography (US) for the detection of blunt intraabdominal injury in pregnant patients and to compare differences between pregnant and nonpregnant patients of childbearing age. MATERIALS AND METHODS: A retrospective review of results of all consecutive emergency blunt trauma US examinations performed at a level I trauma center from January 1995 to June 2002 was conducted. Data on demographics, free fluid location, and patient outcome were collected. Injuries were determined on the basis of results of computed tomography and/or laparotomy. The Student t test was used to detect differences between continuous variables, and chi(2) analysis was used to evaluate differences between proportions. RESULTS: A total of 2319 US examinations for blunt trauma were performed in girls and women between the ages of 10 and 50 years. There were 328 pregnant patients, 23 of whom had intraabdominal injury. The mean age of the pregnant patients was 24.7 years +/- 6.1 (standard deviation) (age range, 14-42 years). In pregnant patients, the sensitivity of US was 61% (14 of 23 patients), the specificity was 94.4% (288 of 305 patients), and the accuracy was 92.1% (302 of 328 patients). Pregnant patients were significantly more likely to have sustained injuries from assault (odds ratio: 2.6, P < .001). The most common pattern of free fluid accumulation detected at US in pregnant patients was that of fluid in the left and right upper quadrants and pelvis (n = 4, 29%); the second most common pattern was one of isolated pelvic fluid (n = 3, 21%). CONCLUSION: For detection of intraabdominal injury, US was less sensitive in pregnant patients than in nonpregnant patients but was highly specific in both subgroups. The sensitivity of US was highest in pregnant patients during the first trimester.

La semilla de Campsiandra angustifolia (Fabaceae: Caesalpiniodeae)como un reflejo de las presiones selectivas sobre su dispersión y establecimiento / The seeds of Campsiandra angustifolia (Fabaceae: Caesalpiniodeae) as a reflex of selective pressures on dispersal and establishment

We indirectly evaluated the selective pressures on dispersal and establishment of Campsiandra angustifolia, a common water-dispersed tree from the Peruvian Amazon, analyzing the variation in the relationship between the volume occupied by dispersal and establishment structures in a total of 535 seeds from 13 trees located at three different habitats. The seeds differed one order of magnitude in their total volume. However, independently of their size and the location of the maternal tree, the relationship between the volume occupied by dispersal and establishment structures was relatively constant (~1) and showed a normal distribution with low skewness, indicating stabilizing selection. These results suggest that, in the habitats studied, dispersal and establishment processes may have similar importance to C.angustifolia. In species with seeds confined in pods, and therefore strongly space-limited, the relative volume of their seeds occupied by dispersal and establishment structures could be a better measure of the trade-off between these two processes than the variation in seed size

Evaluamos indirectamente las presiones selectivas sobre la dispersión y el establecimiento en Campsiandra angustifolia, un árbol de la Amazonía Peruana dispersado por agua, analizando variaciones de la relación entre el volumen ocupado por las estructuras de dispersión y de establecimiento en sus semillas. Medimos un total de 535 semillas de 13 árboles ubicados en tres hábitats diferentes, las cuales presentaron una gran variación en su volumen total. Independientemente del tamaño de la semilla y de la ubicación del árbol de origen, la relación entre el volumen asignado a estructuras de establecimiento y a estructuras de dispersión fue relativamente constante (~1) y presentó una distribución normal con baja asimetría, indicando selección estabilizante. Este resultado sugiere que los procesos de dispersión y establecimiento poseen una importancia relativa similar para C.angustifolia en los hábitats estudiados. En especies con semillas empaquetadas, el volumen relativo ocupado por estructuras relacionadas con la dispersión o el establecimiento podría ser una medida más adecuada de la solución de compromiso entre estos dos procesos que la variación del tamaño de la semilla