Liver injury after an aggressive encounter in male mice

Acute and intense psychological stressors induce cell damage in several organs, including the heart and the liver. Much less is known about social stress. In male mice, aggressive behavior is the most common social stressor. It is remarkable that upon fighting, submandibular salivary glands release a number of peptides into the bloodstream including epidermal growth factor (EGF). We showed previously that released EGF protects the heart from cell damage in this particular stressful situation. Here, we studied the effect of an aggressive encounter on the liver and whether EGF has a similar effect on this organ. An aggressive encounter in male mice caused inflammatory response and a transient increase in plasma alanine and aspartate transaminase activities. At 3 h, focal infiltration of neutrophils was observed in liver parenchyma. These cells accumulate on eosinophilic hepatocytes, which may correspond to dying cells. A few hours later, evidence of necrotic lesion was observed. Surgical excision of submandibular glands, sialoadenectomy, did not prevent the rise in plasma EGF concentration and did not affect the increase in plasma transaminase activities. Neither did the administration of tyrphostin AG-1478 (inhibitor of EGF receptor kinase) alter the increase in plasma alanine transaminase activity. However, it did enhance the rise in both aspartate transaminase and creatine kinase activity, suggesting heart damage. We conclude that an aggressive encounter causes mild liver damage and that released EGF does not protect this organ, in contrast to its effect on the heart.     

Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa

To compare the efficacy of meropenem, ceftazidime, tobramycin and ceftazidime+tobramycin in a guinea-pig model of P. aeruginosa meningitis. After anesthesia, the atlanto-occipital membrane was punctured with a butterfly needle and 100 microl of a solution containing 10(6)CFU/ml of P. aeruginosa were injected directly into the cisterna magna. Four h later, therapy was initiated with saline or antibiotics given im for 48 h in doses that obtained CSF levels as in human meningitis: ceftazidime 200 mg/kg/8h, meropenem 200 mg/kg/8h, tobramycin 30 mg/kg/24h. Tobramycin was also given intracisternally. Animals were sacrificed at different time points. CSF and blood samples were collected and a meningeal swab was performed. Four hours after inoculation, bacterial concentration in CSF was 4 to 5log10CFU and mean WBC was 16,000/-l. All control animals died in 24h with a 12% increase in cerebral edema. All blood-cultures were negative. Ceftazidime, ceftazidime+tobramycin and meropenem reduced the CSF bacterial concentration at 8h by 2.5log10. At 48 h all CSF cultures were sterile but meningeal swab cultures remained positive in 30%. Our results suggest that meropenem may be at least as effective as ceftazidime and that the addition of tobramycin to ceftazidime may improve its efficacy.     

Reproductive cycle and trophic ecology in deep versus shallow populations of the Mediterranean gorgonian Eunicella singularis (Cap de Creus,northwestern Mediterranean Sea)

Coral Reefs - The annual gonad development of a shallow (20 m depth) population of the Mediterranean gorgonian Eunicella singularis was found to be closely synchronized with that of a deep...     

A survey of porcine kidneys and chicken liver for ochratoxin A in Spain

Contamination studies by ochratoxin A on pork kidney and chicken liver has been carried out in Catalonia (Spain). 73% of the pork kidney samples analyzed did not contain an amount of ochratoxin A over our detection limit (0.5 ng/g) whereas only 7% had contamination higher than 1 ng/g. None of the chicken samples analyzed were contaminated by this toxin above the detection limit. All contamination levels found are below the maximum levels accepted by several countries for this kind of material. A confirmative test is necessary before discarding false positive samples.     

Influence of age on ergosterol content in mycelium of Aspergillus ochraceus

Ergosterol has been suggested as a paramoter for studying the content and evolution of fungal infestation in different products. Important differences in this parameter have been described for different genera and species. A study of the relationship between ergosterol content and dry mass in a strain of Aspergillus ochraceus , which is able to produce an antifungal agent, has therefore been carried out in order to use this parameter to accurately evaluate the fungal mass of this strain. We report herein our research work to determine the ergosterol content of the mycelial mass of our mould and how it changes with the fungal age.     

Customized Treatment in Non-Small-Cell Lung Cancer Based on EGFR Mutations and BRCA1 mRNA Expression

Background

Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin. RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1. In order to further examine the effect of EGFR mutations and BRCA1 mRNA levels on outcome in advanced NSCLC, we performed a prospective non-randomized phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. In an exploratory analysis, we also examined the effect of RAP80 and Abraxas mRNA levels.

Methodology/Principal Findings

We treated 123 metastatic non-squamous cell lung carcinoma patients using a customized approach. RNA and DNA were isolated from microdissected specimens from paraffin-embedded tumor tissue. Patients with EGFR mutations received erlotinib, and those without EGFR mutations received chemotherapy with or without cisplatin based on their BRCA1 mRNA levels: low, cisplatin plus gemcitabine; intermediate, cisplatin plus docetaxel; high, docetaxel alone. An exploratory analysis examined RAP80 and Abraxas expression. Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. RAP80 was a significant factor for survival in patients treated according to BRCA1 levels (hazard ratio, 1.3 [95% CI, 1–1.7]; P = 0.05).

Conclusions/Significance

Chemotherapy customized according to BRCA1 expression levels is associated with excellent median and 2-year survival for some subsets of NSCLC patients , and RAP80 could play a crucial modulating effect on this model of customized chemotherapy.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00883480","term_id":"NCT00883480"}}NCT00883480     

From “Shrinks” to “Urban Shamans”: Argentine Immigrants’ Therapeutic Eclecticism in New York City

This article examines Argentine immigrants' reliance on informal networks of care that enable their access to a variety of health providers in New York City (NYC). These providers range from health brokers (doctors known on a personal basis) to urban shamans, including folk healers and fortunetellers of various disciplines. A conceptual framework, based on analysis of social capital categories, is proposed for the examination of immigrants' access to valuable health resources, which are based on relationships of reciprocity and trust among parties. Results revealed immigrants' diverse patterns of health-seeking practices, most importantly their reliance on health brokers, epitomized by Argentine and Latino doctors who provide informal health assistance on the basis of sharing immigrants' social fields and ethnic interests. While mental health providers constitute a health resource shared by Argentines' social webs, urban shamans represent a trigger for the activation of women's emotional support webs. Contrary to the familiar assumption that dense and homogenous networks are more beneficial to their members, this article underscores the advantages of heterogeneous and fluid social webs that connect immigrants to a variety of resources, including referrals to diverse health practitioners.     

Alterations in liver parenchyma after sialoadenectomy in mice: contribution of neutrophils and macrophages to the removal of damaged hepatocytes

Surgical excision of submandibular salivary glands (sialoadenectomy) alters cell turnover in mice liver. Here we show that the liver of adult mice contained scattered leukocyte infiltration foci whose size was in the range of the diameter of hepatocytes. The number of infiltration foci in the liver increased soon after sialoadenectomy and remained high for several weeks. Neutrophils were recruited on dying hepatocytes soon after the initiation of the apoptotic process. Kupffer cells appeared later in the process. Just 2 days after sialoadenectomy, the number of type I infiltration foci (corresponding to the first stage) had increased 5-fold. Since these alterations in liver structure are coincident with a transient decrease in plasma EGF concentration, we studied whether inhibition of EGF receptor by means of genistein injection produced a similar effect. After three days of genistein administration, the number of type I infiltration foci increased 3.5-fold. Sialoadenectomized mice were more susceptible than controls to endotoxin shock. While 90% of sham-operated mice survived a burst of 100 microg lipopolysaccharide/Kg (combined with D-galactosamine 750 mg/Kg), only 50% of sialoadenectomized mice survived. The surviving sialoadenectomized mice recovered more slowly than the controls, as indicated by the high plasma alanine transaminase activity a week after the burst. We conclude that (i) neutrophils and macrophages participate in the process of apoptotic hepatocyte removal in a sequential manner; (ii) although the alteration of liver structure induced by sialoadenectomy is mild, it has delayed consequences on the ability of the liver to deal with aggressive insults.