Endotoxin administration increases hypothalamic somatostatin mRNA through nitric oxide release

Acute inflammation induced by endotoxin (LPS) administration inhibits insulin-like growth factor (IGF-I) and growth hormone (GH) secretion. The aim of this study was to elucidate the role of glucocorticoids and nitric oxide (NO) in the effect of LPS on hypothalamic somatostatin gene expression. Adult male Wistar rats were injected with different doses of LPS (5, 10 and 100 microg/kg). Rats received two i.p. injections of LPS (at 17:30 and 8:30 h the following day) and were killed 4 h after the second injection. LPS administration at the dose of 100 microg/kg increased the hypothalamic somatostatin mRNA content, as well as the serum concentrations of corticosterone. Glucocorticoids do not seem to be involved in LPS-induced increase in hypothalamic somatostatin mRNA since adrenalectomy did not prevent this effect. In order to analyze the possible effect of NO, aminoguanidine, an inducible nitric oxide synthase inhibitor, was injected (100 mg/kg s.c.) simultaneously with LPS injection. Aminoguanidine administration did not modify somatostatin mRNA in saline injected rats, but it prevented LPS-induced increase in hypothalamic somatostatin mRNA. These data suggest that the stimulatory effect of endotoxin on hypothalamic somatostatin gene expression is not mediated by glucocorticoids, but instead by the increase in NO release.     

Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats

Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 microg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin (P < 0.01) and a decrease in serum concentrations of leptin (P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 +/- 0.8 vs. 13.42 +/- 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels (P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10(-7) M) and ghrelin (10(-7) M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells.     

Ghrelin receptor agonist GHRP-2 prevents arthritis-induced increase in E3 ubiquitin-ligating enzymes MuRF1 and MAFbx gene expression in skeletal muscle

Chronic arthritis is a catabolic state associated with an inhibition of the IGF system and a decrease in body weight. Cachexia and muscular wasting is secondary to protein degradation by the ubiquitin-proteasome pathway. The aim of this work was to analyze the effect of adjuvant-induced arthritis on the muscle-specific ubiquitin ligases muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx) as well as on IGF-I and IGF-binding protein-5 (IGFBP-5) gene expression in the skeletal muscle. We also studied whether the synthetic ghrelin receptor agonist, growth hormone releasing peptide-2 (GHRP-2), was able to prevent arthritis-induced changes in the skeletal muscle. Arthritis induced an increase in MuRF1, MAFbx (P < 0.01), and tumor necrosis factor (TNF)-alpha mRNA (P < 0.05) in the skeletal muscle. Arthritis decreased the serum IGF-I and its gene expression in the liver (P < 0.01), whereas it increased IGF-I and IGFBP-5 gene expression in the skeletal muscle (P < 0.01). Administration of GHRP-2 for 8 days prevented the arthritis-induced increase in muscular MuRF1, MAFbx, and TNF-alpha gene expression. GHRP-2 treatment increased the serum concentrations of IGF-I and the IGF-I mRNA in the liver and in the cardiac muscle and decreased muscular IGFBP-5 mRNA both in control and in arthritic rats (P < 0.05). GHRP-2 treatment increased muscular IGF-I mRNA in control rats (P < 0.01), but it did not modify the muscular IGF-I gene expression in arthritic rats. These data indicate that arthritis induces an increase in the activity of the ubiquitin-proteasome proteolytic pathway that is prevented by GHRP-2 administration. The parallel changes in muscular IGFBP-5 and TNF-alpha gene expression with the ubiquitin ligases suggest that they can participate in skeletal muscle alterations during chronic arthritis.     

Resolution of binary mixtures of rifamycin SV and rifampicin by UV/VIS spectroscopy and partial least-squares method (PLS)

A procedure is proposed for the joint determination of rifamycin SV and rifampicin by UV/VIS spectroscopy. A partial least-squares regression (PLS) was used for the resolution of the overlapping spectrophotometric signals from mixtures of the two drugs. The application of a genetic algorithm to select some of the predictor variables allows one to considerably reduce the number of experimental variables, as well as to improve the prediction capacity of the PLS model constructed with these selected potentials. Finally, the methods were applied to the determination of these drugs in biological samples.     

Chemical and structural evolution of humic acids during organic waste composting

The effects of the composting process on the chemical and structural properties of humic acids have been studied in seven different organic waste mixtures from different origin. Only slight changes in elemental composition have been found in the humic acids after the composting process pointing to a more aromatic structure with higher proportions of oxygen and nitrogen. Functional groups were the most sensitive to the changes caused by the composting process showing a marked increase in the total acidity and phenolic, carboxyl and carbonyl groups. Gel permeation chromatography showed a slight increase in the average molecular weight of the humic acids. Infrared spectroscopy did not show important differences in humic acid structure but a clear decrease in the intensity of the bands in the region 3000–2850 cm^-1 corresponding to the aliphatic fractions. As a general result, the composting process yields humic acids in which the elemental and functional composition are closer to that of the more humified soil humic acids.     

PII T-loop mutations affecting signal transduction to NtrB also abolish yeast two-hybrid interactions

Mutations A49P and Delta47-53 at the T loop of the Escherichia coli GlnB (PII) protein impair regulatory interactions with the two-component sensor regulator NtrB (P. Jiang, P. Zucker, M. R. Atkinson, E. S. Kamberov, W. Tirasophon, P. Chandran, B. R. Schepke, and A. J. Ninfa, J. Bacteriol. 179: 4342-4353, 1997). We show here that these mutations also impair interactions between PII and NtrB in the yeast two-hybrid system, indicating that defects in NtrB regulation closely reflect binding impairment. The reported results underline the strength of two-hybrid assays for analysis of interactions involving the T loop of PII proteins.     

Fitting and Calibrating a Multilevel Mixed-Effects Stem Taper Model for Maritime Pine in NW Spain

Stem taper data are usually hierarchical (several measurements per tree, and several trees per plot), making application of a multilevel mixed-effects modelling approach essential. However, correlation between trees in the same plot/stand has often been ignored in previous studies. Fitting and calibration of a variable-exponent stem taper function were conducted using data from 420 trees felled in even-aged maritime pine (Pinus pinaster Ait.) stands in NW Spain. In the fitting step, the tree level explained much more variability than the plot level, and therefore calibration at plot level was omitted. Several stem heights were evaluated for measurement of the additional diameter needed for calibration at tree level. Calibration with an additional diameter measured at between 40 and 60% of total tree height showed the greatest improvement in volume and diameter predictions. If additional diameter measurement is not available, the fixed-effects model fitted by the ordinary least squares technique should be used. Finally, we also evaluated how the expansion of parameters with random effects affects the stem taper prediction, as we consider this a key question when applying the mixed-effects modelling approach to taper equations. The results showed that correlation between random effects should be taken into account when assessing the influence of random effects in stem taper prediction.     

Impact of an Educational Program to Reduce Healthcare Resources in Community-Acquired Pneumonia: The EDUCAP Randomized Controlled Trial

Background

Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge.

Methods

A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed.

Results

We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003).

Conclusions

The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP.

Trial Registration

Controlled-Trials.com ISRCTN39531840     

Nasopharyngeal mucoepidermoid carcinoma: A case report and review of literature

Background

Salivary gland-type tumors originating in the nasopharynx are rare, and only a few articles about mucoepidermoid carcinomas (MEC) in this location have been reported. We describe one case of nasopharyngeal MEC and, based on a review of the literature, discuss different therapeutic approaches that can be taken regarding the result of histological findings, radiological tests and extent of disease.

Case presentation

A 47-year-old woman diagnosed with mucoepidermoid carcinoma of nasopharynx, T1 N3 M0 (stage IV-B) was treated in 2007 with a combination of radiotherapy and chemotherapy to a maximum dose of 70 Gy and concomitant Cisplatin during the radiation. One year later, with the head and neck disease under control, mediastinal nodes relapse appeared which were treated with exclusive radiotherapy to a maximum dose of 65 Gy. One year after the first relapse, a second relapse was detected in the right lung, next to the previously treated mediastinal regions, and the patient initiated a treatment with exclusive chemotherapy based on TPF scheme.

Conclusion

For limited or resectable MEC, combined surgery with radiotherapy, or radiochemotherapy, should be considered the main treatment policy. On the other hand, in poorly differentiated, unresectable tumors or nasopharyngeal MEC, radiochemotherapy could be currently the main treatment approach.     

Circadian Rhythm of Salivary Cortisol in Asian Elephants (Elephas maximus): A Factor to Consider During Welfare Assessment

Elevated glucocorticoid levels during an extended time period might be a stress indicator in nonhuman animals. Therefore, knowledge of the circadian pattern of cortisol secretion is very important to correctly interpret data obtained for welfare assessment of animals in captivity through salivary cortisol. In order to define the circadian rhythm of salivary cortisol secretion in the Asian elephant (Elephas maximus), morning and evening saliva samples of 3 Asian elephants were collected and analyzed by radioimmunoassay. Significantly higher salivary cortisol concentrations were found in the morning than in the evening in all individuals. These results show that salivary cortisol of Asian elephants follows a diurnal pattern of secretion, which could be taken into account when using this methodology to assess welfare in captive Asian elephants.