Fish oil supplement alters markers of inflammatory and nutritional status in colorectal cancer patients

Inflammation is a common feature in cancer. The presence and magnitude of the chronic systemic inflammatory responses may produce progressive nutritional decline. This study aims at investigating whether there are changes in inflammation markers and/or in nutritional status of patients with colorectal cancer undergoing chemotherapy who were supplemented with fish oil. The clinical trial was conducted with 23 patients randomly distributed in 2 groups. The supplemented group (SG) consumed 2 g of fish oil containing 600 milligrams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 9 wk. Nutritional and inflammatory markers status was available, both at a baseline (M0), and after 9 wk of chemotherapy (M9) in the SG and in the nonsupplemented group (NSG). Statistical analysis was conducted with STATA 11.0 software. SG and NSG presented the same baseline characteristics (P > 0.05). Nutritional status indicators such as body mass index and body weight were modified only in the NSG when comparing baseline and M9, P = 0.03 and P = 0.01 respectively, whereas in SG these indicators did not vary. Patients supplemented with fish oil (SG) showed a clinically relevant decrease in the C-reactive protein/albumin relation (P = 0.005). Low doses of fish oil supplement can positively modulate the nutritional status and the C-reative protein/albumin ratio.     

Report on the 1st international workshop on procedures for the development of evidence-based vaccination recommendations, Berlin, Germany, 22-23 November 2010

In November 2010, experts from European and North-American countries met in Berlin, Germany, to discuss improved methods for the development of evidence-based vaccination recommendations. The objectives of the workshop were to (i) review current procedures and experiences of National Immunization Technical Advisory Groups (NITAGs) in developing a framework for evidence-based vaccination recommendations, (ii) discuss the applicability of methods like Grading of Recommendations Assessment, Development and Evaluation (GRADE), and (iii) to identify opportunities for international collaboration to support NITAGs in the development of vaccination recommendations at country-level. Recognizing that a systematic and transparent approach is necessary to promote the quality and acceptance of vaccination recommendations, various decision making frameworks have been implemented by national and international advisory groups addressing common key aspects of knowledge, such as the burden of disease or characteristics of the vaccine. There are several challenges when grading the quality of evidence of some immunization-specific topics (e.g. population-level effects of vaccination). This does not, however, necessitate development of an entirely new systematic methodology. The participants concluded that (i) GRADE or a modification of this methodology is suitable for the grading of quality of evidence related to vaccine effectiveness and safety, and that (ii) international cooperation would be beneficial to develop common framework methodologies for certain aspects of national immunization recommendation developments in order to avoid duplication of efforts, to build on existing strengths, and to support NITAGs worldwide.     

Rapid Secretion of Prestored Interleukin 8 from Weibel-Palade Bodies of Microvascular Endothelial Cells

Interleukin (IL)-8, a C-X-C chemokine, activates integrin-mediated adhesion of neutrophils. Presentation of IL-8 on the endothelial cell surface may promote leukocyte extravasation. We found that cultured human microvascular endothelial cells from the intestine (HIMEC) and from nasal polyps (PMEC), but not human umbilical vein endothelial cells (HUVEC), contained IL-8 in intracellular granules that coexpressed von Willebrand factor (vWf  ). This observation was corroborated by the immunohistochemical observation of double-positive granules (IL-8⁺vWf⁺) in vessels of small and large intestine, nasal mucosa, and skin, whereas umbilical cords revealed no endothelial IL-8. After treatment of HIMEC or PMEC with histamine or thrombin, a dramatic increase in supernatant IL-8 concentration was observed within 3 min, whereas no increase in IL-8 was detected in supernatants of identically treated HUVEC cultures. Histamine or thrombin treatment also caused IL-8–containing granules to rapidly disappear from HIMEC. In HUVEC, IL-8–containing granules were inducible by treatment with recombinant human IL-1β for 24 h; additional histamine treatment doubled IL-8 secretion from HUVEC in the same rapid manner observed for mucosal EC. These data suggested that IL-8 prestored in microvascular endothelial cells may provide a rapid pathway for specific activation of neutrophil adhesion at sites of acute inflammation.     

Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma

The airway mucosal response to allergen in asthma involves influx of activated T helper type 2 cells and eosinophils, transient airflow obstruction, and airways hyperresponsiveness (AHR). The mechanism(s) underlying transient T cell activation during this inflammatory response is unclear. We present evidence that this response is regulated via bidirectional interactions between airway mucosal dendritic cells (AMDC) and T memory cells. After aerosol challenge, resident AMDC acquire antigen and rapidly mature into potent antigen-presenting cells (APCs) after cognate interactions with T memory cells. This process is restricted to dendritic cells (DCs) in the mucosae of the conducting airways, and is not seen in peripheral lung. Within 24 h, antigen-bearing mature DCs disappear from the airway wall, leaving in their wake activated interleukin 2R+ T cells and AHR. Antigen-bearing activated DCs appear in regional lymph nodes at 24 h, suggesting onward migration from the airway. Transient up-regulation of CD86 on AMDC accompanies this process, which can be reproduced by coculture of resting AMDC with T memory cells plus antigen. The APC activity of AMDC can be partially inhibited by anti-CD86, suggesting that CD86 may play an active role in this process and/or is a surrogate for other relevant costimulators. These findings provide a plausible model for local T cell activation at the lesional site in asthma, and for the transient nature of this inflammatory response.     

Ortho substituted polychlorinated biphenyls elevate intracellular [Ca(2+)] in human granulocytes

The perturbation of Ca(2+)-homeostasis in human granulocytes exposed to ortho and non ortho substituted polychlorinated biphenyls (PCB) was investigated. Ortho substituted PCB congeners increased intracellular free calcium, [Ca(2+)]i, in a concentration-dependent manner. The increase in [Ca(2+)]i was inversely proportional to the total surface area of the ortho substituted congeners. The effect of ortho substituted PCB congeners was dependent upon external Ca(2+) and phospholipase C activation, except for a tetra-ortho substituted congener, 2,2',6,6'-TeCB, that was not phospholipase C-dependent. We suppose that PCBs activate phospholipase C which leads to the production of ins(1,4,5)P3. This will release Ca(2+) from intracellular stores and subsequently activation of Ca(2+) release activated Ca(2+) channels (CRAC) in the plasma membrane. It is also possible that PCBs activate CRAC in a more direct manner. Our findings show that ortho substituted PCB congeners stimulate [Ca(2+)]i elevation in human granulocytes, and this could in part account for the effects of PCB on the immune system.     

Analysis of serum concentration of phenobarbital,phenytoin, carbamazepine and carbamazepine 10,11-epoxide by solvent-recycled liquid chromatography

A rapid and precise low cost method for analysing phenobarbital, phenytoin, carbamazepine and carbamazepine 10,11-epoxide using liquid chromatography is described. Recycling reduced the mobile phase consumption by 75%. Recovery was 97.7–101.4% and between days CV was 1.3–1.7%. The retention times of potentially interfering substances are listed.     

Neurophysiological processes underlying the phantom limb pain experience and the use of hypnosis in its clinical management: An intensive examination of two patients

In a pilot study with 2 patients suffering from phantom limb pain (PLP), hypnotic suggestions were used to modify and control the experience of the phantom limb, and positron emission tomography (PET) was used to index underlying pathways and areas involved in the processing of phantom limb experience (PLE) and PLP. The patients' subjective experiences of pain were recorded in a semistructured protocol. PET results demonstrated activation in areas known to be responsible for sensory and motor processing. The reported subjective experiences of PLP and movement corresponded with predicted brain activity patterns. This work helps to clarify the central nervous system correlates of phantom limb sensations, including pain. It further suggests that hypnosis can be incorporated into treatment protocols for PLP.     

Hla class ii alleles and heterogeneity of juvenile rheumatoid arthritis. drb1*0101 may define a novel subset of the disease

Objective. To examine the distribution of HLA class II alleles in clinically distinct juvenile rheumatoid arthritis (JRA) subsets. Methods. We typed 298 patients and 181 controls for HLA–DRB1, DQA1, DQB1, and DPB1 alleles using polymerase chain reaction and oligonucleotide probe techniques. Results. Each JRA subset was characterized by a distinct distribution of HLA class II alleles. For the persistently pauciarticular and rheumatoid factornegative polyarticular JRA subsets, certain combinations of DRB1 and DPB1 alleles were characteristic. In patients without antinuclear antibodies and chronic iridocyclitis, there was an increase of DRB1*0101/02 and DQA1*0101. Conclusion. Findings of HLA typing support clinical subdivisions of the disease and suggest the existence of a novel DRB1*0101/02 and DQA1*0101 associated disease subset.