Expression of Semaphorin 3A and Neuropilin 1 in Asthma

Neuropilin 1 (NP1) is a part of essential receptor complexes mediating both semaphorin3A (SEMA3A) and vascular endothelial growth factor (VEGF) which is one of important mediators involved in the pathogenesis of asthma. Therefore, it is possible that SEMA3A plays a role in the pathogenesis of asthma through attenuation of VEGF-mediated effects. In the present study, we aimed to evaluate expression levels of SEMA3A and NP1 using induced sputum of asthmatics and a murine model of asthma. Firstly, SEMA3A and NP1 expressions in induced sputum of asthmatics and SEMA3A and NP1 expression on bronchoalveolar lavage (BAL) cells and lung homogenates of asthmatic mice were determined. Then we evaluated the immunolocalization of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), and NP1 expressions on asthmatic mice lung tissue and their subcellular distributions using fibroblast and BEAS2B cell lines. Sputum SEMA3A and NP1 expressions were significantly higher in asthmatics than controls. Similarly, SEMA3A and NP1 expressions on BAL cells and lung homogenates were significantly elevated in asthmatic mice compared to control mice. Immunohistochemical analysis showed that VEGFR1, VEGFR2, and NP1 expressions were also uniformly increased in asthmatic mice. Our observations suggest that SEMA3A and NP1 may play important roles in the pathogenesis of asthma.     

ANCA-Negative Wegener's Granulomatosis with Multiple Lower Cranial Nerve Palsies

Wegener''s granulomatosis (WG) is a systemic vasculitis affecting small and medium-sized vessels with granulomatous formation. Though it is known for respiratory tract and kidney involvement, neurologic manifestation has been also reported. Herein we report a patient who suffered pansinusitis with multiple lower cranial nerve palsies but reached remission by immunosuppressant after the diagnosis of WG. A 54-yr-old female visited with headache, hearing difficulty, and progressive bulbar symptoms. She experienced endoscopic sinus surgeries due to refractory sinusitis. Neurologic examination revealed multiple lower cranial nerve palsies. Vasculitic markers showed no abnormality. Nasal biopsy revealed granulomatous inflammation and vasculitis involving small vessels. Given cyclophosphamide and prednisolone, her symptoms were prominently improved. WG should be considered in the patient with multiple cranial nerve palsies, especially those with paranasal sinus disease. Because WG can be lethal if delayed in treatment, prompt immunosuppressant is warranted after the diagnostic tissue biopsy.     

Urinary Biomarkers for Early Detection of Recovery in Patients with Acute Kidney Injury

Urinary biomarkers of acute kidney injury (AKI) have been revealed recently to be useful for prior prediction of AKI. However, it is unclear whether these urinary biomarkers can also detect recovery from established AKI. Urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, were measured every 2 days for 8 days in 66 patients with AKI. At day 0, there were no significant differences in plasma creatinine, BUN, and urine cystatin C between AKI patients in the recovery (n = 33) and non-recovery (n = 33) groups. Plasma creatinine concentrations were significantly lower in the recovery group (3.0 ± 2.0 mg/dL) than in the non-recovery group (5.4 ± 1.9 mg/dL) on day 4 after AKI diagnosis (P < 0.001). In contrast, there were significant differences in urine NGAL between the two groups starting on day 0 (297.2 ± 201.4 vs 407.6 ± 190.4 ng/mL, P = 0.025) through the end of the study (123.7 ± 119.0 vs 434.3 ± 121.5 ng/mL, P < 0.001). The multiple logistic regression analysis showed that urine NGAL could independently predict recovery from AKI. Conclusively, this prospective observational study demonstrates that urine NGAL can be a highly versatile marker for early detection of the recovery phase in established AKI patients.     

The Model for End-Stage Liver Disease Score-Based System Predicts Short Term Mortality Better Than the Current Child-Turcotte-Pugh Score-Based Allocation System during Waiting for Deceased Liver Transplantation

To adopt the model for end-stage liver disease (MELD) score-based system in Korea, the feasibility should be evaluated by analysis of Korean database. The aim of this study was to investigate the feasibility of the MELD score-based system compared with the current Child-Turcotte-Pugh (CTP) based-system and to suggest adequate cut-off to stratify waiting list mortality among Korean population. We included 788 adult patients listed in waiting list in Seoul National University Hospital from January 2008 to May 2011. The short-term survival until 6 months after registration was evaluated. Two hundred forty six (31.2%) patients underwent live donor liver transplantation and 353 (44.8%) patients were still waiting and 121 (15.4%) patients were dropped out due to death. Significant difference was observed when MELD score 24 and 31 were used as cut-off. Three-months survival of Status 2A was 70.2%. However, in Status 2A patients whose MELD score less than 24 (n=82), 86.6% of patients survived until 6 month. Furthermore, patients with high MELD score (≥31) among Status 2B group showed poorer survival rate (45.8%, 3-month) than Status 2A group. In conclusion, MELD score-based system can predict short term mortality better and select more number of high risk patients in Korean population.     

Intrathecal Gabapentin Increases Interleukin-10 Expression and Inhibits Pro-Inflammatory Cytokine in a Rat Model of Neuropathic Pain

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-α, 316.0 ± 69.7 pg/mL vs 88.8 ± 24.4 pg/mL; IL-1β, 1,212.9 ± 104.5 vs 577.4 ± 97.1 pg/mL; IL-6, 254.0 ± 64.8 pg/mL vs 125.5 ± 44.1 pg/mL; IL-10, 532.1 ± 78.7 pg/mL vs 918.9 ± 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.     

A Simplified Formula Using Early Blood Gas Analysis Can Predict Survival Outcomes and the Requirements for Extracorporeal Membrane Oxygenation in Congenital Diaphragmatic Hernia

The aims of this study were to investigate whether early arterial blood gas analysis (ABGA) could define the severity of disease in infants with congenital diaphragmatic hernia (CDH). We conducted a retrospective study over a 21-yr period of infants diagnosed with CDH. Outcomes were defined as death before discharge, and extracorporeal membrane oxygenation requirements (ECMO) or death. A total 114 infants were included in this study. We investigated whether simplified prediction formula [PO₂-PCO₂] values at 0, 4, 8, and 12 hr after birth were associated with mortality, and ECMO or death. The area under curve (AUC) of receiver operating characteristic curve was used to determine the optimum ABGA values for predicting outcomes. The value of [PO₂-PCO₂] at birth was the best predictor of mortality (AUC 0.803, P < 0.001) and at 4 hr after birth was the most reliable predictor of ECMO or death (AUC 0.777, P < 0.001). The value of [PO₂-PCO₂] from ABGA early period after birth can reliably predict outcomes in infants with CDH.