Jo H. A. J. Curfs

Recombinant Murine Granulocyte Colony-Stimulating Factor Protects against Acute Disseminated Candida albicans Infection in Nonneutropenic Mice

The effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on acute disseminated Candida albicans infection in nonneutropenic mice was investigated. Mice treated with a single dose of rG-CSF showed a significantly reduced mortality (28% vs. 90%; P < .001). The outgrowth of C. albicans from the kidneys, spleens, and livers of rG-CSF-treated mice was significantly reduced (log cfu/g of kidney, 5.54 vs. 7.13; P < .001), as were circulating tumor necrosis factor-alpha and interleukin-1beta. After rG-CSF, the kidneys showed fewer infectious infiltrates, enhanced granulocyte influx, and almost complete absence of hyphal outgrowth. During peritoneal C. albicans infection, rG-CSF enhanced influx of granulocytes to the site of infection, and exudate granulocytes showed increased oxygen radical production. These results indicate that rG-CSF enhances host resistance to disseminated candidiasis in nonneutropenic mice through activation of granulocytes and their recruitment to the site of infection.

Phagocytosis and killing of Candida albicans by human neutrophils after exposure to structurally different lipid emulsions.

BACKGROUND To test the hypothesis that structurally different lipid emulsions have distinct immune-modulating properties, we analyzed the elimination of Candida albicans by neutrophils after exposure to various emulsions. METHODS Neutrophils from 8 volunteers were incubated in physiologic 5 mmol/L emulsions containing long-chain- (LCT), medium-chain- (MCT), mixed LCT/MCT-, alpha-tocopherol-enriched LCT/MCT (LCT/MCT-E), or structured lipids (SL). After washing, the neutrophils were incubated with C. albicans. Phagocytosis was measured as the number of yeast-associated neutrophils relative to the total neutrophil count. Killing was expressed as the percentage of Candida survival relative to the initial yeast cell count. RESULTS No significant differences in yeast-neutrophil association could be demonstrated after neutrophil incubation in various lipid emulsions or medium, after correction for non-specific adhesion. However, although Candida survival after 1 hour incubation with non-lipid-exposed neutrophils amounted to 53% +/- 11% and was not influenced by LCT (60% +/- 11%), LCT/MCT (78% +/- 7%), LCT/MCT-E (72% +/- 12%), and SL (67% +/- 6%), pure MCT (70% +/- 13%) significantly impaired the killing capacity of neutrophils. CONCLUSIONS The decreased killing capacity of neutrophils after exposure to medium-chain fatty acid-containing emulsions and the absence of this effect with LCT suggest that lipid emulsions influence the elimination of C. albicans depending on the triglyceride chain length.

Functional and morphological monocyte abnormalities in a patient with malakoplakia

netic resonance images of bone marrow in vertebral bones and femora were entirely normal. Ultrasonography of the abdomen did not show any organ involvement or detectable lymphadenopathy. Endoscopic examination of the upper gastrointestinal tract did not reveal any alterations. With these results, the patient was diagnosed with primary pulmonary plasmacytoma, and the intermittent administration of melphalan and prednisolone (MP) was introduced. After six cycles of therapy, the patient became free of complaints, and there was a remarkable improvement of reticulonodular infiltrate on chest roentgenograms and a reduction of serum IgA concentrations. At the submission of this report, the patient has received 16 cycles of the MP therapy and is alive and well. Differential diagnosis in the present case should include pulmonary small lymphocytic lymphoma with plasmacytoid differentiation (6,7). However, in diffuse small lymphocytic lymphoma, tumor cells express surface immunoglobulins, mostly IgM (8), and the isotype of paraprotein detected in such patients has been reported to be exclusively IgM (7). The present case has shown a good clinical response to melphalan-based chemotherapy, which may also support the diagnosis of plasmacytoma. Our experience implies that pulmonary plasmacytoma has to be considered for differential diagnosis in patients with diffuse pulmonary infiltrates accompanied by monoclonal gammopathy.

Advances in Understanding the Pathogenesis of Pneumococcal Otitis Media

In this review, a state of the art on otitis media research is provided with emphasis on the role of Streptococcus pneumoniae in the pathogenesis of this disease. Articles have been selected by MEDLINE search supplemented with a manual crosscheck of bibliographies. Pathogenic mechanisms in middle ear and eustachian tube are described. Furthermore, pneumococcal characteristics and pneumococcus–host interactions are highlighted as well as the possible role of biofilms in persistence or recurrence of otitis media. Because of the availability of new techniques, an increasing number of pneumococcal features contributing in the pathogenesis of otitis media are identified and in-depth knowledge of pneumococcus–host interactions has been gained. The present advances in research on otitis media open up new perspectives for therapeutic or preventive strategies.

Differences in Endolymphatic Sac Mitochondria-Rich Cells Indicate Specific Functions

Objective/Hypothesis The purpose of the study was to examine the specific involvement of endolymphatic sac mitochondria‐rich cells in endolymph homeostasis.

Genetic Relatedness between Pneumococcal Populations Originating from the Nasopharynx, Adenoid, and Tympanic Cavity of Children with Otitis Media

ABSTRACT Previous studies have shown that Streptococcus pneumoniae exists in both middle ear effusions and the upper respiratory region from children with otitis media with effusion (OME), but it remains unclear whether these strains represent genetically identical clones. Therefore, it cannot be determined whether these bacteria originate from a common source. To determine the presence of pneumococci at different anatomical locations of OME patients, conventional culture and PCR techniques were used. To analyze the possible genetic relatedness between pneumococci from different anatomical sites, molecular typing by amplified fragment length polymorphism was utilized. The percentage of middle ear effusions of OME patients that are positive for pneumococci after PCR analysis (13%) was higher than after conventional culture (5%). Molecular fingerprints from pneumococci derived from two different anatomic sites within patients were very similar in 80% of OME patients and in 90% of acute otitis medium patients, indicating their genetic relatedness. Biofilm formation or pneumococcal L-forms probably play a role in OME, since culture-negative effusions prove to contain pneumococcal DNA. Bacteria involved in this process most likely originate from the nasopharynx since they show a close genetic relatedness with their nasopharyngeal counterparts.

Effects of interleukin-8 on nonspecific resistance to infection in neutropenic and normal mice.

The effect of treatment with interleukin-8 (IL-8), a neutrophil-activating cytokine, was investigated in normal and neutropenic mice infected with a lethal dose of Pseudomonas aeruginosa, Klebsiella pneumoniae, or Plasmodium berghei. Intraperitoneal (i.p.) IL-8 treatment was associated with accelerated death when IL-8 was administered shortly before i.p. infection with P. aeruginosa or shortly after i.p. infection with P. aeruginosa and K. pneumoniae. Histopathological analyses demonstrated a tendency to more severe organ lesions in IL-8-treated mice. Only nonneutropenic mice that received IL-8 shortly before the infectious challenge and at the site of infection were protected by IL-8. Whether IL-8 is protective of or detrimental to the survival of infection appeared to depend on the presence of bacteria at the injection site and on the presence of neutropenia. IL-8 may be an important participant in the cascade of interacting cytokines that is induced by the lethal infectious challenge. Images

Parenteral Administration of Medium- but Not Long-Chain Lipid Emulsions May Increase the Risk for Infections by Candida albicans

ABSTRACT Intravenous administration to volunteers of an emulsion of medium-chain lipids, but not of an emulsion of pure long-chain lipids or a placebo, increased the growth of Candida albicans in serum and modulated Candida-induced cytokine production by mononuclear cells in a way suggesting that medium-chain, but not long-chain, triglycerides increase the risk for infections by Candida.

Genetic disorders of transporters/channels in the inner ear and their relation to the kidney

Inner ear physiology is reviewed with emphasis on features common to renal physiology. Genetic disorders in transporters/channels for chloride (ClC-K), bicarbonate (Cl-/HCO3- exchanger), protons (H+-ATPase), sodium (ENaC, NKKC1, NBC3, NHE3), potassium (KCNQ1/KCNE1, Kcc4), and water (AQP4) in the inner ear and their relation to the kidney are discussed. Based on data from human disorders (with or without mouse counterparts) and mouse models (without human counterparts) this article focuses on the involvement of these transporters/channels in hearing loss.

With Medium-Chain Triglycerides, Higher and Faster Oxygen Radical Production by Stimulated Polymorphonuclear Leukocytes Occurs

BACKGROUND Parenteral lipid emulsions are suspected of suppressing the immune function. However, study results are contradictory and mainly concern the conventional long-chain triglyceride emulsions. METHODS Polymorphonuclear leukocytes were preincubated with parenteral lipid emulsions. The influence of the lipid emulsions on the production of oxygen radicals by these stimulated leukocytes was studied by measuring chemiluminescence. Three different parenteral lipid emulsions were tested: long-chain triglycerides, a physical mixture of medium- and long-chain triglycerides, and structured triglycerides. Structured triglycerides consist of triglycerides where the medium- and long-chain fatty acids are attached to the same glycerol molecule. RESULTS Stimulated polymorphonuclear leukocytes preincubated with the physical mixture of medium- and long-chain triglycerides showed higher levels of oxygen radicals (p < .005) and faster production of oxygen radicals (p < .005) compared with polymorphonuclear leukocytes preincubated with long-chain triglycerides or structured triglycerides. Additional studies indicated that differences in results of various lipid emulsions were not caused by differences in emulsifier. The overall production of oxygen radicals was significantly lower after preincubation with the three lipid emulsions compared with controls without lipid emulsion. CONCLUSIONS A physical mixture of medium- and long-chain triglycerides induced faster production of oxygen radicals, resulting in higher levels of oxygen radicals, compared with long-chain triglycerides or structured triglycerides. This can be detrimental in cases where oxygen radicals play either a pathogenic role or a beneficial one, such as when rapid phagocytosis and killing of bacteria is needed. The observed lower production of oxygen radicals by polymorphonuclear leukocytes in the presence of parenteral lipid emulsions may result in immunosuppression by these lipids.