IL-13 induces expression of CD36 in human monocytes through PPARgamma activation

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARgamma pathway was demonstrated using transfection of a PPARgamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice. We also show that CD36 induction by IL-13 via PPARgamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARgamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARgamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.     

Inactivated Francisella tularensis live vaccine strain protects against respiratory tularemia by intranasal vaccination in an immunoglobulin A-dependent fashion

Francisella tularensis is a gram-negative intracellular bacterium that is considered to be a potential category A biological weapon due to its extreme virulence. Although vaccination with the attenuated live vaccine strain (LVS) of F. tularensis can protect against lethal challenge, use of inactivated or subunit forms as vaccine candidates for induction of protective antibody responses has not been fully evaluated. In the present study, we examined whether immune protection in the lung could be stimulated by intranasal administration of inactivated LVS together with interleukin-12 (IL-12) as an adjuvant. LVS was inactivated by heat, paraformaldehyde treatment, or exposure to UV, and inactivation of the preparations was confirmed by assessing bacterial growth and the survival of mice after direct inoculation. We found that mucosal vaccination with inactivated LVS provided 90 to 100% protection in mice after lethal intranasal challenge with 10(4) CFU of LVS, and this protection was dependent on inclusion of exogenous IL-12 during vaccine administration. Survival of vaccinated mice after live bacterial challenge was correlated with reduced bacterial burden, decreased pulmonary inflammation, increased serum antibody titers, and lower levels of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and IL-6 in the lungs, livers, and spleens. Whereas NK cells were primarily responsible for the production of IFN-gamma in unvaccinated, challenged animals, vaccinated mice had increased levels of lung IFN-gamma+ CD4+ T cells after challenge. Significantly, mice genetically deficient in immunoglobulin A (IgA) expression were unable to survive lethal challenge after vaccination. These results are the first results to demonstrate that IgA-mediated protection against lethal respiratory tularemia occurs after mucosal vaccination with inactivated F. tularensis LVS.     

Detection of Rickettsia rickettsii and Bartonella henselae in Rhipicephalus sanguineus ticks from California

Sixty-two questing adult Rhipicephalus sanguineus (Latreille) ticks were collected by direct removal from blades of turfgrass and adjacent concrete walkways at a suburban home in Riverside County, CA, and tested for the presence of Rickettsia, Bartonella, and Ehrlichia DNA. Polymerase chain reaction (PCR) was used to amplify fragments of the 17-kDa antigen gene and the rOmpA gene of the spotted fever group rickettsiae. One male tick contained R. rickettsii DNA; its genotype differed from R. rickettsii isolates found in Montana and Arizona that cause Rocky Mountain spotted fever and from Hlp#2 and 364D serotypes. One male tick and one female tick contained B. henselae DNA. No Ehrlichia platys or Ehrlichia canis DNAs were detected using nested PCR for their 16S rRNA genes. These findings extend the area where Rickettsia rickettsii may be vectored by Rh. sanguineus. Rh. sanguineus also may be infected with Bartonella henselae, a human pathogen that is typically associated with fleas and causes cat scratch disease.     

Bone formation after sinus augmentation with engineered bone

Objectives: The aim of the following investigation was to quantify the resorption rate of tissue-engineered bone grafts in the maxillary sinus using volume measurements. MATERIAL AND METHODS: Sinus floor augmentation using autologous bone grafts from the iliac crest (n=17, group 1) was compared with commercially produced transplants of human cells seeded on polyglycolid-polylactid (PLGA) scaffolds (Oral Bone) (n=14, group 2). RESULTS: The total resorption rate for autologous transplants 3 months post operation was 29%, while the tissue-engineered bone showed a resorption rate of 90%. The autologous bone had a bone density of up to 266-551 Hounsfield units (HU), while sufficient mineralization of tissue-engineered bone was found in only one case (152 HU). CONCLUSION: In this clinical study, the use of autologous cancellous bone grafts in sinus augmentation was more reliable than scaffolds containing cultured osteoblasts. Further tissue-engineered bone transplants should be examined to draw general conclusions about the use of tissue-engineered grafts compared with autologous bone grafts for maxillary sinus augmentation.     

Heads or tails, does it make a difference? Capsule endoscope direction in small bowel studies is important

Capsule endoscopy has opened the small bowel for direct inspection. However, the diagnostic sensitivity of capsule endoscopy is not 100 %. We have observed that forward orientation and backward orientation of the camera in the small bowel provide different information on pathological findings. Double-head capsule endoscopy may offer the answer to this problem.     

Left subclavian artery stenting: an option for the treatment of the coronary-subclavian steal syndrome

Introduction

The subclavian steal syndrome is characterized by the vertebral artery flow inversion, due to a stenotic lesion in the origin of the subclavian artery. The Coronary-subclavian Steal Syndrome is a variation of the Subclavian Steal Syndrome and is characterized by inversion of flow in the Internal Thracic artery that has been used as conduct in a myocardial revascularization. Its diagnosis must be suspected in patients with difference in pulse and arterial pressure in the upper limbs, that present with angina pectoris and that have done a myocardial revascularization. Its treatment must be a surgical bypass or a transluminal angioplasty.

Objective

The objective is to show the left subclavian artery stenting as a safe and effective method to treat the coronary-subclavian steal syndrome.

Methods

Historical prospective, non-randomized trial, through revision of the hospital records of the patients treated with the stenting of the left subclavian artery, from January 2006 to September 2012.

Results

In the mentioned period, 4.291 miocardial revascularizations were performed with the use of the left mammary artery, and 16 patients were identified to have the Coronary-subclavian steal syndrome. All of them were submitted to endovascular treatment. The success rate was 100%; two patients experienced minor complications; none of them presented with major complications. Eleven of the 16 patients had ultrassonographic documentation of patent stent for at least one year; two patients lost follow up and other two died.

Conclusion

The stenting of the left subclavian artery is a good option for the treatment of the Coronary-subclavian Steal Syndrome, with high level of technical and clinical success.     

Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial

Background and aims  The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349–353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival. Materials and methods  Stages I–III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m² plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m² given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3). Results  The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015). Conclusions  The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer. M. Lorenz deceased.