Pneumocystis Pneumonia in a Non-Immunocompromised Lung Cancer Patient after Surgery: A Case Report.

We present the Pneumocystis pneumonia case of a 64-year-old man with no remarkable history except for hypertension, who had not undergone any treatment other than surgery. On postoperative day 7, high-resolution computed tomography findings revealed multifocal ground-glass opacifications with interlobular septal thickening in both lungs; therefore, atypical pneumonia was suspected. Polymerase chain reaction (PCR) test performed after bronchoalveolar lavage was positive for Pneumocystis jirovecii (P. jirovecii). Based on the PCR results, a final diagnosis of Pneumocystis pneumonia (PCP) was made. After treatment, he improved and was discharged. This is a unique case of PCP diagnosis in a non-immunocompromised patient, with no remarkable history except for hypertension, who had not undergone any treatment other than surgery for cancer. Thus, it is necessary to consider additional risk factors for PCP and timing of preventive treatment.

Polyhexamethylene guanidine phosphate-induced necrosis may be linked to pulmonary fibrosis.

Following the humidifier disinfectant incident in Korea, polyhexamethylene guanidine phosphate (PHMG-P) has been used to establish lung fibrosis model animals. Herein, we investigated time-dependent changes after a single PHMG-P instillation (22 µg/lung) to identify the underlying pathogenesis and immune response involved in PHMG-P-induced lung fibrosis. Compared to control mice, body weight loss and blood biochemical and hematological changes were more remarkable in PHMG-P-instilled mice, an increase of total cell counts, infiltration of macrophages and neutrophils and necrotic cell death were also more notable in the lungs of PHMG-P-instilled mice. Pathological lesions were detected from Day 1 after exposure, deteriorating with time. In addition, secretion of anti-inflammatory mediators was rapidly inhibited from 6 h after exposure, and level of IL-24, a tissue repair-related cytokine, was up-regulated in the lungs of PHMG-P-instilled mice until Day 21 post-exposure. In vitro tests using BEAS-2B cells showed that PHMG-P disturbed structural and functional homeostasis of organelles and that intracellular ROS increase was considered as an important cause of PHMG-P-induced cell death. Additionally, co-culture with DNA, a polyanionic compound, clearly inhibited PHMG-P-induced necrosis, and increased IL-1ß and TNF-α level and decreased IL-6 and IL-8 levels were observed following exposure to PHMG-P. Meanwhile, IL-8 secretion increased in cells exposed to PHMG-P-induced cell debris. Therefore, we suggest that necrotic cell debris may importantly contribute to the PHMG-P-induced inflammatory response and pathogenesis. In addition, PHMG-P-induced necrosis may be initiated by high affinity between PHMG-P and cell membrane.

Low-dose hydrocortisone treatment for patients with septic shock: a pilot study comparing 3days with 7days.

BACKGROUND AND OBJECTIVE: Although there is controversy regarding the benefit of low-dose corticosteroid therapy in patients with septic shock, the Surviving Sepsis Campaign has advocated that low-dose intravenous hydrocortisone be used to treat adult septic shock patients. This study investigated the effect of the duration of a stress dose of hydrocortisone on survival of septic shock patients with relative adrenal insufficiency. METHODS: One hundred and thirty consecutive patients who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock were included in the study. An additional inclusion criterion was vasopressor support after fluid resuscitation. The primary end-point was 28-day mortality, and the secondary end-points were shock reversal and mortality in the intensive care unit and hospital. All eligible patients were prospectively randomized to receive hydrocortisone treatment for 3 or 7days. Hydrocortisone treatment was started at a dose of 50mg every 6h. RESULTS: Baseline data at recruitment did not differ between the two groups. After 28days, mortality did not differ between the 3- and 7-day treatment groups (33.8% vs 36.9%, P=0.629). Mortality rates in the intensive care unit and hospital did not differ significantly between the two groups. The median time to withdrawal of vasopressor therapy was 5.0days in the 3-day treatment group and 6.4days in the 7-day treatment group (P=0.102). CONCLUSIONS: This pilot study showed that in patients with septic shock and relative adrenal insufficiency, 28-day mortality did not differ between those treated with low-dose hydrocortisone for 3 or 7days.

Immunomodulatory effects of polar lichens on the function of macrophages in vitro.

Lichen species were collected from King George Island (Antarctica) and were screened for their immunomodulatory effect. Among the lichens tested, the methanol extract (CR-ME) of Caloplaca regalis showed the highest nitric oxide (NO) production in murine peritoneal macrophages. Therefore, this study further examined the ability of C. regalis to induce secretory and cellular responses in macrophages. Macrophages were treated with various concentrations of CR-ME for 18 h. The CR-ME treatment induced tumoricidal activity and increased the production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide by macrophages. However, CR-ME had a little effect on the levels of reactive oxygen species, interleukin-1 and IFN-gamma in CR-ME-treated macrophages. The CR-ME-induced tumoricidal activity was partially abrogated by a NO inhibitor and the anti-TNF-alpha antibody. Thus, the tumoricidal effect of CR-ME appeared to be mainly mediated by NO and TNF-alpha production from macrophages. Treating the macrophages with a p38 mitogen-activated protein kinase (MAPK) inhibitor partially blocked the tumoricidal activation induced by CR-ME, whereas inhibitors of the other kinases did not have an inhibitory effect. These results suggest that CR-ME induces the tumoricidal activity via the p38 MAPK-dependent pathway. Furthermore, electrophoretic mobility shift assay analyses revealed that the CR-ME treatment induced the activation of the NF-kappaB transcription factor. Overall, these results indicate that the tumoricidal activity induced by CR-ME is mainly due to TNF-alpha and NO production, and the activation of macrophage by CR-ME is mediated probably via the p38 MAPK and NF-kappaB pathway. Our results may also provide some leads in the development of new immunomodulating drugs.

ATP degradation products as freshness indicator of flatfish during storage.

In this study, the ATP degradation products and microbial growth during storage of flatfish were measured for assessing its freshness. LOD and LOQ of the ATP degradation products including ADP, AMP, IMP, HxR and Hx were 0.01-0.11 and 0.02-0.37 µg/g respectively, and the recovery ranged from 35.8 to 98.8%. The Hx level increased significantly during the storage period, regardless of storage temperature (p < 0.05). The initial Hx level was 245.27 µg/g, and this rapidly increased to 2563.72, 6643.69, and 4236.65 µg/g at 4, 10, and 25 °C at 14 days, 8 days, and 12 h, respectively. The correlation coefficient (R 2) between microbial growth and Hx percentage ranged from 0.7709 to 0.8939. Based on the nitroblue tetrazolium colorimetric assay, the optical density of flatfish stored at 4 °C increased from 2.45 to 13.29 at 82 h of storage, which was equivalent to 442% increment.

Red ginseng acidic polysaccharide (RGAP) in combination with IFN-gamma results in enhanced macrophage function through activation of the NF-kappaB pathway.

This study examined the effects of red ginseng acidic polysaccharide (RGAP) on macrophage-mediated cytotoxicity towards murine melanoma B16 cells. RGAP alone had no effect on killing of tumor cells. RGAP treatment increased the production of interleukin-1 (IL-1), IL-6, and nitric oxide (NO) by macrophages, whereas tumor necrosis factor (TNF-alpha) and reactive oxygen species (ROS) production were not changed by RGAP. However, treatment of macrophages with a combination of RGAP and recombinant interferon-gamma (rIFN-gamma) enhanced killing of tumor cells. In addition, the combination treatment showed marked cooperative induction of IL-1, IL-6, TNF-alpha, and NO production. Electrophoretic mobility shift assay analysis revealed that treatment of macrophages with RGAP plus rIFN-gamma induced the activation of the nuclear factor-kappa B (NF-kappaB) transcription factor. In agreement with this, the combination treatment resulted in increased NF-kappaB-p65 expression. The present results demonstrate synergistic effects on macrophage function of RGAP in combination with rIFN-gamma, and suggest that NF-kappaB plays an important role in mediating these effects. These data also support the development of clinical studies of this combination.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

A limited series of synthetic tetrahydroisoquinoline alkaloids reduce inflammatory gene iNOS via inhibition of p-STAT-1 and suppress HMGB1 secretion in LPS-treated mice lung tissue.

Tetrahydroisoquinoline alkaloids (THIs) have shown to increase survival and beneficial effect on animal model of sepsis, partly due to heme oxygenase-1 (HO-1) induction. Here, we aimed to compare a limited series of synthesized THIs on HO-1 induction and inhibitory effect of iNOS and COX-2 expression in lipopolysaccharide (LPS)-activated RAW264.7 cells. To the end, most promising compound (THI-61) was tested whether this compound reduces iNOS protein expression and inflammatory markers (HMGB1, TNF-α) in LPS-treated mice lung tissue. The results indicated that N-carbonyl substituted THI seem to affect HO-1 induction depending on which functional group is attached to C1 position. All compounds that reduce LPS-activated NF-κB-luciferase activity showed to preferential inhibition of iNOS/NO but not COX-2/PGE2 that was partly related to inhibition of STAT-1 phosphorylation. In particular, THI-61 induced translocation of Nrf2 from cytosol into the nucleus by an increased Nrf2-ARE binding activity, and reduced IL-1ß production in LPS-activated RAW264.7 cells. The reduced expression of iNOS/NO by THI-61 was reversed by siHO-1RNA-transfection. In LPS-treated mice, THI-61 significantly reduced iNOS protein in lung tissues, and HMGB1 and TNF-α levels in the BALF. We concluded that 1) lipophilic moiety of 1C substituent is much more important in N-carbonyl substituted THI for induction of HO-1, 2) newly synthesized THI-61 may be beneficial for treatment of lung injury.

The Study on Inhibition of Planktonic Bacterial Growth by Non-Thermal Atmospheric Pressure Plasma Jet Treated Surfaces for Dental Application.

Investigation of the effects by non-thermal atmospheric pressure plasma jet (NTAPPJ) treatment on the titanium dental implant surfaces for the inhibition of two common pathogens related with dental infections, Streptococcus mutans and Staphylococcus aureus, was carried out in this study. The commercially pure titanium was used as specimen, which were irradiated by NTAPPJ for 30, 60 and 120 seconds. Specimen without being treated with NTAPPJ was assigned as the control group. The X-ray photoelectron spectroscope and surface contact angle goniometer were used to analyze the effects of NTAPPJ treatment on surface chemistry and hydrophilicity of the specimen. The effects of the NTAPPJ treatment on surfaces, in terms of bacterial attachment, growth, morphology and structural changes were evaluated by the number of colony forming units (CFU) and scanning electron microscopy (SEM) observations. The results showed that there was a reduction of CFUs and the significant change in morphology of bacteria as they were cultured on the titanium surfaces treated with NTAPPJ. These results were related to surface chemical changes and hydrophilicity changes by NTAPPJ. The NTAPPJ treatment is very effective on the dental implant titanium surface treatment that resulted in the inhibition of bacteria and has a great potential to be a promising technique in various clinical dental applications.

Quality evaluation of noble mixed oil blended with palm and canola oil.

Noble blended oils (canola: palm oil = 3:7, 4:6, 5:5, 6:4 and 7:3) were prepared and their frying qualities were evaluated. Frying qualities such as fatty acid composition, acid value, peroxide value, viscosity, smoke point, color, antioxidant activity, and sensory evaluation were measured to elucidate the optimum blend ratio of canola and palm oil. The ratio of unsaturated to saturated fatty acid of the blended oils was higher than that of palm oil after frying 50 times. The blended oil (3:7, Ca: Pa) had a relatively high oxidative stability and its peroxide values were 44.2-70.7 meq/kg after frying. The 3:7 (Ca: Pa) blended oil had excellent flavor, taste, and texture compared to those of the other frying oils as a result of a sensory evaluation of raw and fried potatoes. The results suggest that the 3:7 (Ca: Pa) blended oil is a good alternative oil for frying potatoes.

Protective effect of protocatechuic acid isopropyl ester against murine models of sepsis: inhibition of TNF-alpha and nitric oxide production and augmentation of IL-10.

Antioxidants have been shown to be effective in murine models of sepsis. Protocatechuic acid has antioxidant activity. In the present study, the protective effects of protocatechuic acid and its derivatives were investigated in a mouse model of septic shock induced by lipopolysaccharide (LPS)/D-galactosamine (GalN). Pretreatment of animals with protocatechuic acid effectively suppressed LPS/GalN-induced lethality; protocatechuic acid isopropyl ester was the most effective among the various derivatives of protocatechuic acid. Protocatechuic acid isopropyl ester was also effective in protection against the high-dose LPS-induced shock. Pretreatment with protocatechuic acid isopropyl ester effectively suppressed the LPS/GalN-induced increase in plasma tumor necrosis factor (TNF)-alpha alanine aminotransferase (ALT), nitrite/nitrate levels, and hepatic malondialdehyde levels. In contrast, it markedly enhanced the LPS/GalN-induced increase in plasma interleukin (IL)-10 levels, without any changes in IL-6 plasma levels. These results suggest that protocatechuic acid isopropyl ester could be useful for the prevention of sepsis.