Both IL-1β and TNF-α Regulate NGAL Expression in Polymorphonuclear Granulocytes of Chronic Hemodialysis Patients

Background. NGAL is involved in modulation of the inflammatory response and is found in the sera of uremic patients. We investigated whether hemodiafiltration (HDF) could influence the ability of polymorphonuclear granulocytes (PMGs) to release NGAL. The involvement of interleukin- (IL-)1β and tumor necrosis factor- (TNF-)α on NGAL release was evaluated. Methods. We studied end-stage renal disease (ESRD) patients at the start of dialysis (Pre-HDF) and at the end of treatment (Post-HDF) and 18 healthy subjects (HSs). Peripheral venous blood was taken from HDF patients at the start of dialysis and at the end of treatment. Results. PMGs obtained from ESRD patients were hyporesponsive to LPS treatment, with respect to PMG from HS. IL-1β and TNF-α produced by PMG from post-HDF patients were higher than those obtained by PMG from pre-HDF. Neutralization of IL-1β, but not of TNF-α, determined a clear-cut production of NGAL in PMG from healthy donors. On the contrary, specific induction of NGAL in PMG from uremic patients was dependent on the presence in supernatants of IL-1β and TNF-α. Conclusion. Our data demonstrate that in PMG from healthy subjects, NGAL production was supported solely by IL-1β, whereas in PMG from HDF patients, NGAL production was supported by IL-1β, TNF-α

Role of Paricalcitol in Modulating the Immune Response in Patients with Renal Disease

Introduction. The aim was to highlight the existence of a relationship between vitamin D deficiency, chronic inflammation, and proteinuria, by measuring neutrophil gelatinase associated lipocalin (NGAL) and common inflammatory markers after administration of paricalcitol, a vitamin D analog, in vivo and in vitro. Methods. 40 patients with end-stage chronic kidney disease (CKD) and secondary hyperparathyroidism and 40 healthy subjects were enrolled. Serum calcium, phosphorus, 25(OH)-vitamin D, parathyroid hormone (PTH), erythrocyte sedimentation rate, high-sensitivity C-reactive protein, interleukin-(IL-) 17, IL-6, IL-1 , interferon-gamma (IFN-), tumor necrosis factor-alpha (TNF-), plasmatic and urinary NGAL, and 24 h albuminuria and proteinuria were measured before and 24 h after an intravenous bolus of paricalcitol (5 mcg). Human peripheral blood mononuclear cells were isolated and stimulated with phytohaemagglutinin. NGAL, IL-1 , IL-17, IL-6, TNF-, and IFN-were measured in the culture medium and in the 24 h urine collection. Results. 25(OH)-vitamin D was lower in CKD than in controls ( < 0.0001), while inflammatory markers were higher in CKD group ( < 0.0001). In vivo and in vitro studies showed a downregulation of NGAL, IL-17, IL-6, IL-1 , TNF-, and IFN-after paricalcitol administration ( < 0.0001). Conclusions. 25(OH)-vitamin D regulates immune and inflammatory processes. Further studies are needed to confirm these data in order to improve the treatment of CKD patients

Enterococcal meningitis caused by Enterococcus casseliflavus. First case report

BACKGROUND: Enterococcal meningitis is an uncommon disease usually caused by Enterococcus faecalis and Enterococcus faecium and is associated with a high mortality rate. Enterococcus casseliflavus has been implicated in a wide variety of infections in humans, but never in meningitis. CASE PRESENTATION: A 77-year-old Italian female presented for evaluation of fever, stupor, diarrhea and vomiting of 3 days duration. There was no history of head injury nor of previous surgical procedures. She had been suffering from rheumatoid arthritis for 30 years, for which she was being treated with steroids and methotrexate. On admission, she was febrile, alert but not oriented to time and place. Her neck was stiff, and she had a positive Kernig's sign. The patient's cerebrospinal fluid was opalescent with a glucose concentration of 14 mg/dl, a protein level of 472 mg/dl, and a white cell count of 200/μL with 95% polymorphonuclear leukocytes and 5% lymphocytes. Gram staining of CSF revealed no organisms, culture yielded E. casseliflavus. The patient was successfully treated with meropenem and ampicillin-sulbactam. CONCLUSIONS: E. casseliflavus can be inserted among the etiologic agents of meningitis. Awareness of infection of central nervous system with Enterococcus species that possess an intrinsic vancomycin resistance should be increased

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Colon cancer stem cells: promise of targeted therapy.

First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed to its epitope AC133. It is not clear if CD133 is a marker of colon CSCs-other cell surface markers, such as epithelial-specific antigen, CD44, CD166, Musashi-1, CD29, CD24, leucine-rich repeat-containing G-protein-coupled receptor 5, and aldehyde dehydrogenase 1, have been proposed. In addition to initiating and sustaining tumor growth, CSCs are believed to mediate cancer relapse after chemotherapy. How can we identify and analyze colon CSCs and what agents are being designed to kill this chemotherapy-refractory population

Almond Skin Inhibits HSV-2 Replication in Peripheral Blood Mononuclear Cells by Modulating the Cytokine Network

We have investigated the effect of almond skin extracts on the production of pro-inflammatory and anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). PBMCs were either infected or not by herpes simplex virus type 2 (HSV-2), with and without prior treatment with almond skin extracts. Production of IL-17 induced by HSV-2 was inhibited by natural skins (NS) treatment. NS triggered PBMC in releasing IFN-α, IFN-γ and IL-4 in cellular supernatants. These results may explain the antiviral potential of almond skins

Role of Th cytokines in thyroid autoimmunity

Thyroid autoimmunity occurs when the immune system reacts against thyroid cells after targeting them like any other “not-self” antigen. To define a thyroid autoimmune disorder is often difficult even if the presence of auto-antibodies and/or autoreactive lymphocytes is a common feature. Although the pathogenetic mechanism is poorly understood, increasing evidences indicate that apoptosis is one of the key process that leads to thyroid auto-immunity. Afterward, Th cytokines have been considered the regulator factors of the cell survival in thyroid autoimmunity. Understanding the cell response from the perspective of type 1 or type 2 cytokines could clarify the pathogenetic mechanism controlling thyroid autoimmunity and define new therapeutic approache

Chryseobacterium indologenes bacteraemia in a diabetic child

Chryseobacterium indologenes is a non-fermentative Gram-negative bacillus that is a rare pathogen in humans. Its occurrence in diabetic children has not been previously reported. In this report, a case is described of C. indologenes bacteraemia possibly associated with the use of a peripheral venous catheter. A 2-year-old boy with type I diabetes mellitus was admitted due to a coma caused by cerebral oedema and was successfully treated for his neurological condition but presented on the tenth day after admission with fever of 40 degrees C, agitation, restlessness, lack of appetite, somnolence and fatigue. His pulse rate was 90 min(-1) and his respiratory rate was 20 min(-1). Laboratory studies revealed a white blood cell count of 4900 mm(-3) with 67% neutrophils and 27% lymphocytes. Two separate blood cultures yielded C. indologenes. Treatment with ceftriaxone was started before the culture results were obtained, and was continued after susceptibility test results were obtained. The patient became afebrile after 48 h, and his general condition improved within 36 h. The infection did not recur. This is believed to be the third case of bacteraemia outside of Asia due to C. indologenes and the first in a diabetic child not otherwise immunocompromised. This case indicates that C. indologenes infection can occur in diabetic children without ventilator or central venous catheter and might be treated with a single agent after in vitro susceptibility tests have been performed

Crucial role of interleukin-4 in the survival of colon cancer stem cells

Colon tumors may be maintained by a rare fraction of cancer stem-like cells (CSC) that express the cell surface marker CD133. Self-renewing CSCs exhibit relatively greater resistance to clinical cytotoxic therapies and recent work suggests that this resistance may be mediated in part by an autocrine response to the immune cytokine interleukin 4 (IL-4). Blocking IL-4 signaling can sensitize CSCs to apoptotic stimuli and increase the in vivo efficacy of cytotoxic therapy. These findings suggest that inhibitors of IL-4 signaling may offer a new therapeutic tool in colon carcinom