A Comparison of Palliative Stenting or Emergent Surgery for Obstructing Incurable Colon Cancer

Background  

Acute colonic obstruction because of advanced colonic malignancy is a surgical emergency. Our aim was to review our experience with self-expanding metal stents (SEMS) compared to emergent surgery as the initial therapy for the management of patients with incurable obstructing colon cancer.     

Polarization dictates iron handling by inflammatory and alternatively activated macrophages

Background

Macrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes.

Design and Methods

Inflammatory/M1 and alternatively activated/M2 macrophages were propagated in vitro from mouse bone-marrow precursors and polarized in the presence of recombinant interferon-γ or interleukin-4. We characterized and compared their ability to handle radioactive iron, the characteristics of the intracellular iron pools and the expression of molecules involved in internalization, storage and export of the metal. Moreover we verified the influence of iron on the relative ability of polarized macrophages to activate antigen-specific T cells.

Results

M1 macrophages have low iron regulatory protein 1 and 2 binding activity, express high levels of ferritin H, low levels of transferrin receptor 1 and internalize – albeit with low efficiency -iron only when its extracellular concentration is high. In contrast, M2 macrophages have high iron regulatory protein binding activity, express low levels of ferritin H and high levels of transferrin receptor 1. M2 macrophages have a larger intracellular labile iron pool, effectively take up and spontaneously release iron at low concentrations and have limited storage ability. Iron export correlates with the expression of ferroportin, which is higher in M2 macrophages. M1 and M2 cells activate antigen-specific, MHC class II-restricted T cells. In the absence of the metal, only M1 macrophages are effective.

Conclusions

Cytokines that drive macrophage polarization ultimately control iron handling, leading to the differentiation of macrophages into a subset which has a relatively sealed intracellular iron content (M1) or into a subset endowed with the ability to recycle the metal (M2).     

Characterisation of clinical and food animal Escherichia coli isolates producing CTX-M-15 extended-spectrum β-lactamase belonging to ST410 phylogroup A

Seven phylogroup A CTX-M-15-producing Escherichia coli isolates recovered from clinical and meat samples were further characterised. All of them belonged to sequence type ST410. Only 2 of the 22 virulence genes investigated were detected. All isolates carried the fimH gene encoding type 1 fimbriae, and five isolates harboured the iucD gene encoding aerobactin siderophore. A group of five isolates showed 81.2% similarity by pulsed-field gel electrophoresis (PFGE), comprising three clinical isolates belonging to ONT:H9 and two food isolates belonging to O55:H9. Different HpaI digestion patterns were observed for plasmids, but all of them belonged to IncFIB group and harboured bla(CTX-M-15) associated with bla(OXA-1), bla(TEM), tetA, catB3 and aac(6')-Ib surrounded by an identical genetic environment. These findings showed the possibility of lateral gene transfer of bla(CTX-M-15) as well as other antibiotic resistance determinants between low-virulence food and clinical isolates.     

Metabolism of ethanol to acetaldehyde by rat uterine horn subcellular fractions

Controversial studies from others suggested that alcohol intake could be associated with some deleterious effects in the uterus. Not all the effects of alcohol drinking on female reproductive organs can be explained in terms of endocrine disturbances. Deleterious effect of alcohol or its metabolites in situ could also play a role. Accordingly, we found a metabolism of alcohol to acetaldehyde in the rat uterine horn tissue cytosolic fraction mediated by xanthine oxidoreductase, requiring a purine cosubstrate and inhibited by allopurinol. This activity was detected by histochemistry in the epithelium and aldehyde dehydrogenase activity was detected in the muscular layer and in the serosa. There was a microsomal process, not requiring NADPH and of enzymatic nature, oxygen-dependent and inhibited by diethyldithiocarbamate, diphenyleneiodonium and partially sensitive to esculetin and nordihydroguaiaretic acid. The presence of metabolic pathways in the uterine horn able to generate acetaldehyde, accompanied by a low capacity to destroy it through aldehyde dehydrogenase, led to acetaldehyde accumulation in the uterus during ethanol exposure. Results suggest that any acetaldehyde produced in situ or arriving to the uterine horn via blood would remain in this organ sufficiently to have the opportunity to react with critical molecules to cause deleterious effects.     

Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Recent clinical and laboratory studies have shown that the effects of naltrexone for alcoholism may be moderated by the Asn40Asp single-nucleotide polymorphism (SNP) of the μ-opioid receptor gene (OPRM1). Allele frequencies for this polymorphism, however, have been shown to vary substantially as a function of ethnic background, such that individuals of Asian descent are more likely to carry the minor (Asp40) allele. The objective of this study is to test the naltrexone pharmacogenetic effects of the Asn40Asp SNP in a sample of Asian Americans. This study consists of a double-blinded, randomized, placebo-controlled laboratory trial of naltrexone. Participants (n=35, 10 females; 13 Asn40Asn and 22 Asp40 carriers) were non-treatment-seeking heavy drinkers recruited from the community. After taking naltrexone or placebo, participants completed an intravenous alcohol administration session. The primary outcome measures were subjective intoxication and alcohol craving. Results suggested that Asp40 carriers experienced greater alcohol-induced sedation, subjective intoxication, and lower alcohol craving on naltrexone, as compared to placebo, and to Asn40 homozygotes. There results were maintained when controlling for ALDH2 (rs671) and ADH1B (rs1229984) markers and when examining the three levels of OPRM1 genotype, thereby supporting an OPRM1 gene dose response. These findings provide a much-needed extension of previous studies of naltrexone pharmacogenetics to individuals of Asian descent, an ethnic group more likely to express the minor allele putatively associated with improved biobehavioral and clinical response to this medication. These findings help further delineate the biobehavioral mechanisms of naltrexone and its pharmacogenetics.     

Quantitation of infectious myonecrosis virus in different tissues of naturally infected Pacific white shrimp, Litopenaeus vannamei, using real-time PCR with SYBR Green chemistry

The Pacific white shrimp, Litopenaeus vannamei, is the most important shrimp species in volume in world aquaculture. However, in recent decades, outbreaks of diseases, especially viral diseases, have led to significant economic losses, threatening the sustainability of shrimp farming worldwide. In 2004, Brazilian shrimp farming was seriously affected by a new disease caused by the Infectious myonecrosis virus (IMNV). Thus, disease control based on rapid and sensitive pathogen detection methods has become a priority. In this study, a specific quantitation method for IMNV was developed using real-time PCR with SYBR Green chemistry and viral load of the principal target tissues of chronically infected animals was quantified. The quantitative analysis revealed that mean viral load ranged from 5.08 × 10⁸ to 1.33 × 10⁶ copies/μg of total RNA in the hemolymph, 5.096 × 10⁵ to 1.26 × 10³ copies/μg in the pleopods, 6.85 × 10⁸ to 3.09 × 10⁴ copies/μg in muscle and 8.15 × 10⁶ to 3.90 × 10³ copies/μg in gills. Different viral loads of IMNV were found with greater values in the hemolymph and muscle, followed by the pleopods and gills.     

Neuroanatomical substrates involved in cannabinoid modulation of defensive responses

Administration of Cannabis sativa derivatives causes anxiolytic or anxiogenic effects in humans and laboratory animals, depending on the specific compound and dosage used. In agreement with these findings, several studies in the last decade have indicated that the endocannabinoid system modulates neuronal activity in areas involved in defensive responses. The mechanisms of these effects, however, are still not clear. The present review summarizes recent data suggesting that they involve modulation of glutamate and GABA-mediated neurotransmission in brain sites such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of the stria terminalis, hippocampus and dorsal periaqueductal gray. Moreover, we also discuss results indicating that, in these regions, the endocannabinoid system could be particularly engaged by highly stressful situations.     

Angiotensin‐converting enzyme inhibition increases glucose‐induced insulin secretion in response to acute restraint

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