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Purpose: We aimed to report the clinical and immunological characteristics of variant type X91+ chronic granulomatous disease (CGD) in a Chinese cohort. Methods: The clinical manifestations and immunological phenotypes of patients with X91+ CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91phox protein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 and flow cytometry. Results: Patients with X91+ CGD accounted for 8% (7/85) of all patients with CGD. The median age of onset in the seven patients with X91+ CGD was 4 months. Six patients received the BCG vaccine, and 50% (3/6) had probable BCG infections. Mycobacterium tuberculosis infection was prominent. The most common sites of infection were the lung (6/7), lymph nodes (5/7), and soft tissue (3/7). Two patients experienced recurrent oral ulcers. The stimulation index (SI) of the patients with X91+ CGD ranged widely from 1.9 to 67.3. The difference in the SI among the three groups of patients (X91+ CGD, X91− CGD, and X910 CGD) was statistically significant (P = 0.0071). The three groups showed no significant differences in onset age, diagnosis age, or severe infection frequency. CYBB mutations associated with X91+ CGD were commonly located in the second transmembrane or intracellular regions. Three novel X91+ CGD–related mutations (c.1462–2 A > T, c.1243C > T, and c.925G > A) were identified. Conclusions: Variant type X91+ CGD may result in varied clinical manifestations. Moreover, the laboratory findings might indicate a moderate neutrophil SI. We should deepen our understanding of variant X91+ CGD to prevent missed diagnoses. [ABSTRACT FROM AUTHOR]

Purpose: This is a functional characterization of a novel CYBA variant associated with normal DHR flow cytometry. Chronic granulomatous disease (CGD) is an inborn error of immunity characterized by recurrent bacterial and fungal infections and dysregulated inflammatory responses due to defective phagocytic cell function leading to the formation of granulomas. CGD patients have pathogenic variants in any of the five components of the phagocytic NADPH oxidase, which transfers electrons through the phagosomal membrane and produces superoxide upon bacterial uptake. Here, we report a pediatric female patient with a novel homozygous missense variant (c.293C > T, p.(Ser98Leu)) in CYBA, encoding the p22phox protein, associated with autosomal recessive CGD. Methods and Results: The patient presented with severe recurrent pneumonia. Specific pathogens identified included Burkholderia and Serratia species suggesting neutrophil functional abnormalities; however, the dihydrorhodamine-1,2,3 (DHR) flow cytometric and cytochrome c reduction assays for neutrophil respiratory burst fell within the low side of the normal range. Western blot and flow cytometric analysis of individual NADPH oxidase components revealed reduced levels of p22phox and gp91phoxphox proteins. The pathological consequence of the p.Ser98Leu variant was further evaluated in heterologous expression systems, which confirmed reduced p22phox protein stability and oxidase activity. Conclusions: Although this patient did not exhibit all the classic features of CGD, such as granulomas and skin infections, she had recurrent pneumonias with oxidant-sensitive pathognomonic organisms, resulting in appropriate targeted CGD testing. This case emphasizes the need to contextually interpret laboratory data, especially using clinical findings to direct additional assessments including genetic analysis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Neutrophil modulation of pancreatic acini has not been investigated before. [•] Neutrophil respiratory burst blocked calcium oscillations in pancreatic acini. [•] Neutrophil respiratory burst had no effect on calcium oscillations in hepatocytes. [•] Neutrophil respiratory burst leads to secretory blockade in pancreas. [ABSTRACT FROM AUTHOR]

Abstract: The pathophysiology underlying the high incidence of post-stroke infectious complications has not been fully understood. We measured the respiratory burst of neutrophils as an index of their bactericidal function in patients with haemorrhagic stroke, and we also measured the plasma concentrations of noradrenalin, cortisol and neutrophil function-related amino acids. Blood samples were obtained from patients who underwent emergency craniotomies for haemorrhagic stroke (n =11) or CT-guided stereotaxic aspiration of intracerebral haematomas (n =6). Neutrophils were isolated, and their chemiluminescence response to N-formyl-methionyl-leucyl-phenylalanine was measured. Healthy volunteers served as controls (n =15). In patients with stroke, the chemiluminescence response of the isolated neutrophils was significantly lower than in the controls, and it was significantly inversely correlated with the plasma noradrenalin concentration. By Day 30, this value approached control levels. Other parameters measured were not significantly correlated with the chemiluminescence response. Stroke-induced suppression of the neutrophil respiratory burst may be responsible for frequent post-stroke infectious complications. [Copyright &y& Elsevier]

Summary: N,N-Dialanyl protoporphyrin (PP(Ala)2) and diarginine diprotoporphyrinate (PP(Arg)2) are porphyrin photosensitizers that are currently being used in the photodynamic therapy (PDT) of cancer. In the present study, the effects of these agents on the neutrophil respiratory burst in vitro were investigated. In the case of non-stimulated neutrophils, the respiratory burst was significantly increased in the presence of PP(Ala)2 in concentration 5.0mg/l, while in the presence of PP(Arg)2 in the same concentration it did not change. By contrast, both photosensitizers decreased a respiratory burst by neutrophils stimulated with opsonized zymosan. Pre-irradiation of solutions of PP(Ala)2 and PP(Arg)2 with ultraviolet A did not alter the observed responses. The prooxidative effect of PP(Ala)2 is probably due to the stimulation of protein kinase C, which plays a key role in the respiratory burst of non-stimulated cells, whereas the antioxidant effect of both photosensitizers may be explained by their inhibitory effect on EGFR tyrosine kinase, which plays an important role in the respiratory burst of cells stimulated by opsonized zymosan. The lack of effect of the two dyes after UV-A pre-irradiation may be due to rapid self-quenching of UV-A-excited dye molecules to the ground state. The results of this study provide a starting point for experiments in animal models aimed at determining the clinical importance of the observed effects in cancer diagnosis and therapy. [Copyright &y& Elsevier]

Background. Bioincompatibility of hemodialysis (HD) membranes is responsible for neutrophil activation leading to oxidative stress, which can be further increased by intravenous (IV) iron (Fe) administration. The aim of our study was to monitor neutrophil respiratory burst during HD and to find out whether this process is influenced by IV Fe and oral vitamin E administration. Methods. Within four HD sessions, blood samples were taken from seven chronic HD patients at time 0 (before HD), 60, 70, and 130 min of HD session. Neutrophil administration attenuates this fluctuation of neutrophil oxidative metabolism, without affecting the total degree of oxidative stress. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to investigate neutrophil respiratory burst activity (NRBA) in workers who were occupationally exposed to formaldehyde. Methods: NRBA, spontaneous and stimulated with E. coli, N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA), was studied by means of quantitative flow cytometric determination in 29 workers who were occupationally exposed to formaldehyde; 21 healthy subjects, not exposed to formaldehyde, served as controls. All subjects underwent clinical assessment, including a review of a summary of their medical history and a physical examination. Routine haematological tests were performed. Results: A statistically significant predominance of subjective symptoms and objective clinical findings of chronic upper respiratory tract inflammation, as well as decreased resistance to infections, was observed in the 29 workers exposed to formaldehyde, compared with the controls (X2 = 9.28, P = 0.02). No statistically significant difference in the spontaneous and stimulated NRBA between the exposed workers and the control group was observed. The spontaneous NRBA (percentage oxidizing cells) was significantly lower in the group of exposed workers with upper respiratory tract findings and frequent and long-lasting infectious inflammatory relapses (median and range 0.45 (0.02-2.03), mean values 0.65 ± 0.74) than in the healthy controls (median and range 1.35 (0.07-8.69), mean values 2.42±2.47; P < 0.05), and in the group of exposed workers with rare and short, acute, inflammation of the upper respiratory tract or without any inflammations (median and range 1.00 (0.02-8.67), mean values 1.67 ±2.08; P<0.05). A significant negative correlation between the duration of occupational exposure to formaldehyde and erythrocyte count and haematocrit was found. Conclusions: The observed decrease of spontaneous NRBA in workers with a history and clinical findings of frequent and long-lasting relapses of chronic inflammation of the upper respiratory tract could be due to formaldehyde exposure and individual susceptibility. The results obtained suggest that functional changes in polymorphonuclear neutrophil granulocytes could serve as an early indicator of an impact of formaldehyde on NRBA. The applied method might be used for identifying groups at increased toxicological risk. [ABSTRACT FROM AUTHOR]

Rebamipide protects gastrointestinal mucosal integrity against reactive oxygen species (ROS). The effect of rebamipide on the capability of PMNs to produce ROS in the presence of plasma and rectal dialysates (RD) of control and ulcerative colitis (UC) subjects was evaluated. We recruited six healthy volunteers for obtaining PMNs, control plasma, and control RD and six patients with inactive UC for obtaining plasma and RD. PMNs were activated using fMLP, and ROS was measured by fluorescent microplate assay (DCFD). Rebamipide significantly inhibited the neutrophil respiratory burst by 45%. Plasma from both control subjects and UC patients significantly blunted the fMLP-induced respiratory burst. However, the plasma of the UC patients was significantly less inhibitory than the plasma of control subjects. RD from control subjects significantly blunted the fMLP-induced respiratory burst while, RD from patients with UC did not. Rebamipide maintained its antioxidant effects in the presence of plasma or RD obtained from both controls and UC patients. In conclusion, partial loss of the inhibitory effects of plasma and RD in patients with UC may contribute to oxidative-induced tissue damage in UC and rebamipide antioxidant properties were not hampered by the biological milieu of patients with UC. [ABSTRACT FROM AUTHOR]

Leukocyte functions were investigated in patients with oral candidiasis (OC), recurrent aphthous ulcers (RAU) and oral lichen planus (OLP). Blastogenesis and lymphokine-activated killer (LAK) activity were decreased in RAU and OLP compared with healthy controls, and lymphocytes from patients with OC exhibited the lowest blastogenesis and LAK activity. Neutrophil superoxide (O2-) generation showed the following relationship: healthy controls > RAU ≅ OLP > OC patients. No great differences in phagocytosis or natural killer (NK) activity were observed among patients and healthy controls, although NK activity in controls was slightly higher than in patients. In OC, all suppressed leukocyte functions improved with the disappearance of the clinical manifestations. However, in RAU there were no significant differences before and after treatment except for O2- generation. These results indicate that OC tends to occur in individuals predisposed to fungal infections and that the pathophysiology of both RAU and OLP is associated with leukocyte suppression. [ABSTRACT FROM AUTHOR]

Abstract: Two new benzofuran derivatives, 2-(4′-hydroxybenzyl)-5,6-methylenedioxy-benzofuran ( 1 ) and 2-(4′-hydroxybenzoyl)-5,6-methylenedioxy-benzofuran ( 2 ), along with 8 known compounds were isolated from 60% EtOH extract of the fibrous roots of Liriope spicata var. prolifera. Their structures were elucidated on the basis of extensive spectroscopic analysis. In an in vitro bioactive assay, the two new benzofuran derivatives showed anti-inflammatory activity. Compounds 1 and 2 exhibited significant inhibitory activity against neutrophil respiratory burst stimulated by phorbol 12-myristate 13-acetate (PMA) with IC50 value of 4.15±0.07 and 5.96±0.37μM, respectively. [Copyright &y& Elsevier]