Quantitative NBT reduction test with or without stimulation of peripheral polymorphonuclear cells from pregnant women

We performed the nitroblue tetrazolium (NBT) reduction test to investigate the function of polymorphonuclear cells (PMN) from prenatal, intrapartal, postpartal and nonpregnant women with or without stimulation by phorbol myristate acetate (PMN). The capacity for NBT reduction of PMN was significantly increased in pregnancy, followed by a further increases during labor without any stimulation. On the other hand, when stimulated with PMA, there were no differences between pregnancy and labor in the reactivities of PMNs, although they were still significantly higher than those of nonpregnant women. Kallikrein increased the activity of PMN in an in vitro study, suggesting that it may be associated with the change in PMN function in labor.     

Laparoscopic surgery for perforated peptic ulcer

Laparoscopic surgery has become the treatment of choice for the management of perforated peptic ulcer. The advantages of laparoscopic repair for perforated peptic ulcer include less pain, a short hospital stay, and an early return to normal activity. Although the operation time of laparoscopic surgery is significantly longer than that of open surgery, laparoscopic technique is safe, feasible, and with morbidity and mortality comparable to that of the conventional open technique. To benefit from the advantages offered by minimally invasive laparoscopic technique, further study will need to determine whether laparoscopic surgery is safe in patients with generalized peritonitis or sepsis.     

Intracranial invasive aspergillosis originating in the sphenoid sinus: a successful treatment with high-dose itraconazole in three cases

We report three cases of intracranial aspergillosis originating in the sphenoid sinus in immunocompetent patients. The patients presented with an orbital apex syndrome in that a unilateral loss of vision and cranial nerve III palsy were seen in all cases and a contralateral involvement was also seen in one case. Despite the initial treatment with a conventional dose of itraconazole (ITCZ, 200 mg/day), the neurological deficits failed to improve and the granulomatous inflammation was not suppressed. Therefore, we treated with a combination of a high dose of ITCZ at 500-1000 mg/day (16-24 mg/kg/day) and amphotericin B (AMPH-B) at 0.5 mg/kg/day, in conjunction with a pulse dose of methylprednisolone at 1000 mg/day. Two cases responded favorably in that the ocular movements completely recovered, and their maximum serum concentrations of the hydroxy ITCZ were 7816 ng/ml and 5370 ng/ml. However, the other case worsened, despite ITCZ treatment at 16 mg/kg/day, and the serum concentration of the hydroxy ITCZ was 3863 ng/ml. The surgical decompression of the cavernous sinus via an extradural approach was performed, and the dose of ITCZ was increased to 24 mg/kg/day. The resulting serum concentration of the hydroxy ITCZ was 4753 ng/ml, and the outcome of this case has been favorable. These results suggest that a high blood level of the hydroxy ITCZ (more than 4500 ng/ml) is a prerequisite for the successful treatment of intracranial aspergillosis and that the combination treatment of ITCZ with AMPH-B would be preferred. The concomitant use of steroid and/or surgical decompression should be considered, if the invasiveness is not well-controlled in spite of intensive medical therapy.     

Effects of DQ-113, a new quinolone, against methicillin- and vancomycin-resistant Staphylococcus aureus-caused hematogenous pulmonary infections in mice

We compared the effects of DQ-113, a new quinolone, to those of vancomycin (VCM) and teicoplanin (TEIC) in murine models of hematogenous pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and VCM-insensitive S. aureus (VISA). The MICs of DQ-113, VCM, and TEIC for MRSA were 0.125, 1.0, and 0.5 microg/ml, respectively; and those for VISA were 0.25, 8.0, and 8.0 microg/ml, respectively. Treatment with DQ-113 resulted in a significant decrease in the number of viable bacteria in the lungs of the mice used in the MRSA infection model (counts in mice treated with DQ-113, VCM, and TEIC and control mice, 6.33 +/- 0.22, 7.99 +/- 0.14, 7.36 +/- 0.20, and 8.47 +/- 0.22 log10 CFU/lung [mean +/- standard error of the mean], respectively [P<0.01 for the group treated with DQ-113 compared with the group treated with VCM or TEIC or the untreated group]). Mice infected with VISA were pretreated with cyclophosphamide, and the survival rate was recorded daily for 10 days. At the end of this period, 90% of the DQ-113-treated mice were still alive, whereas only 45 to 55% of the mice in the other three groups were still alive (P<0.05 for the group treated with DQ-113 compared with the group treated with VCM or TEIC or the untreated group]). DQ-113 also significantly (P<0.05) reduced the number of viable bacteria in the lungs compared with those in the lungs of the other three groups (counts in mice treated with DQ-113, VCM, and TEIC and control mice, 5.76 +/- 0.39, 7.33 +/- 0.07, 6.90 +/- 0.21, and 7.44 +/- 0.17 log10 CFU/lung, respectively). Histopathological examination revealed milder inflammatory changes in DQ-113-treated mice than in the mice in the other groups. Of the antibiotics analyzed, the parameters of area under the concentration-time from 0 to 6 h (AUC(0-6))/MIC and the time that the AUC(0-6) exceeded the MIC were the highest for DQ-113. Our results suggest that DQ-113 is potent and effective for the treatment of hematogenous pulmonary infections caused by MRSA and VISA strains.     

Measurement of lysophospholipase D/autotaxin activity in human serum samples

OBJECTIVES: Lysophospholipase D (lysoPLD)/autotaxin regulates the blood levels of lysophosphatidic acid (LPA), and we designed a serum lysoPLD assay for use in clinical laboratory testing. DESIGN AND METHODS: LysoPLD activity was assessed based on the amount of choline released with lysophosphatidylcholine as the substrate. RESULTS AND CONCLUSIONS: It was confirmed that the lysoPLD assay can be applied to clinical laboratory testing. The serum lysoPLD activity in healthy female subjects was significantly higher than that in the male subjects.     

A single amino acid alteration in cytoplasmic domain determines IL-2 promoter activation by ligation of CD28 but not inducible costimulator (ICOS)

The CD28 family molecules, CD28, and inducible costimulator (ICOS) all provide positive costimulatory signals. However, unlike CD28, ICOS does not costimulate IL-2 secretion. The YMNM motif that exists in the CD28 cytoplasmic domain is a known binding site for phosphatidylinositol 3-kinase (PI3-K) and Grb2. ICOS possesses the YMFM motif in the corresponding region of CD28 that binds PI3-K but not Grb2. We postulated that the reason that ICOS does not have the ability to induce IL-2 production is because it fails to recruit Grb2. To verify this hypothesis, we generated a mutant ICOS gene that contains the CD28 YMNM motif and measured IL-2 promoter activation after ICOS ligation. The results indicated that ICOS became competent to activate the IL-2 promoter by this single alteration. Further analysis demonstrated that Grb2 binding to ICOS was sufficient to activate the NFAT/AP-1 site in the IL-2 promoter and that the cytoplasmic domain of CD28 outside of the YMNM motif is required for activation of the CD28RE/AP-1 and NF-kappaB sites. Together, these observations lead us to believe that the difference of a single amino acid, which affects Grb2 binding ability, may define a functional difference between the CD28- and ICOS-mediated costimulatory signals.     

Inspired superoxide anions attenuate blood lactate concentrations in postoperative patients

OBJECTIVE: Low concentrations of superoxide (O(2)(-)) constitute a portion of atmosphere negative ions in the form of O(2)-(H(2)O)(n), which has been reported to have a stimulatory effect on superoxide dismutase activity. If superoxide dismutase is activated by inspired negative ions containing O(2)(-), aerobic metabolism could be improved. To test this hypothesis, we examined blood lactate concentrations in postoperative patients with or without inhalation of air from a home humidifier that generates O(2)-(H(2)O)(n). DESIGN: Prospective, randomized, controlled trial. SETTING: Neurosurgical intensive care unit of a general hospital. PATIENTS: Twenty postneurosurgical patients with arterial blood lactate concentrations >1.5 mmol/L were studied and were divided randomly into two groups. INTERVENTIONS: One group received 40 L/min 40% oxygen flow from a home humidifier as an oxygen therapy for 4 hrs, followed by almost the same flow from a jet nebulizer, which generates positive ions, for 4 hrs. The other group received the reverse combination. MEASUREMENTS AND MAIN RESULTS: During the 8-hr study, arterial blood lactate concentrations were measured every hour. There was a significant difference in the time course of blood lactate concentrations between the groups. In the group in which negative ions were first initiated for 4 hrs and positive ions thereafter, the lactate concentration decreased slightly at 3, 4, and 5 hrs and returned to the baseline concentration thereafter. In the group with the reverse combination, the lactate concentration did not change during the first 4 hrs but decreased thereafter after inhalation of negative ions. CONCLUSIONS: Inspired O(2)(-) attenuates blood lactate concentrations. This may be attributed, in part, to the systemic stimulatory effect on superoxide dismutase activity, which accelerates oxidative phosphorylation in the mitochondria, thus attenuating lactate generation.