The Timing of Femur Fracture Fixation is an Important Factor for Prolonged Mechanical Ventilation

PURPOSE@#Mechanical ventilation (MV) is an essential life-saving modality for severely injured patients. However, the long-term use of MV is a major risk factor for late mortality. The surgical correction of long bone fractures plays a critical role not only in improving functional outcomes, but also in reducing physiological derangements, including MV duration. This study investigated the factors affecting prolonged MV (PMV) in severely injured patients with femur fractures.@*METHODS@#We retrospectively evaluated all severely injured patients (injury severity score >15) with femur fractures who were taken to the emergency department within 12 hours of the causative accidents between January 2016 and December 2018. PMV was defined as MV lasting for ≥7 days. We analyzed the factors affecting PMV.@*RESULTS@#In total, 35 patients were enrolled and 21 (33.3%) were included in the PMV group. The PMV group required more red blood cell (RBC) transfusions within 7 days RBC (7dRBC) (12.8 vs. 6.8 units; p=0.03) and the time to femur fracture fixation (TFFF) was longer (7.9 vs. 2.7 days; p=0.018). The area under the curve (AUC) for TFFF was 0.740 (95% confidence interval [CI]: 0.572–0.908; p=0.018) and the AUC for 7dRBC was 0.718 (95% CI: 0.546–0.889; p=0.031).@*CONCLUSIONS@#This study indicates that TFFF is an independent risk factor for PMV. Early fixation of femur fractures might prevent PMV and its associated complications.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of β-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of WNT/β-catenin and STAT signaling.

Interactions of Nitric Oxide and Antioxidants in Hypoxia-Reoxygenation Injury

PURPOSE: An ischemia-reperfusion injury leads to profound functional and structural alterations of vascular smooth muscle cells (VSMC). It is still not clear whether hypoxia- reoxygenation and antioxidants affect the nitric oxide (NO) synthesis of VSMC. This study tried to investigate the effects of antioxidants on NO production, inducible nitric oxide synthase (iNOS) and the expression of NFkappaB p65, during the hypoxia-reoxygenation of VSMC cultures. METHODS: The VSMCs were primarily cultured from rat aortae, and confirmed by immunoreaction with the anti- smooth muscle myosin antibody. The condition of the hypoxia was verified by measuring the PO2 and PCO2 of the culture media. The concentrations of nitrite in the culture media were measured by the Griess reaction. Western blottings for the iNOS and NFkappaB p65 proteins were performed. L-NAME was used as an NOS inhibitor. Vitamins C and E, Glutathione (GSH), lipoic acid and dihydrolipoic acid (DHLA) were used as antioxidants. RESULTS: The iNOS protein was induced in the VSMC by 24 hours of hypoxia, which increased the nitrite in the VSMC culture medium. The reoxygenation profoundly increased the iNOS protein expression and nitrite concentration. The L- NAME, vitamins C and E, GSH, lipoic acid and DHLA decreased the nitrite productions during hypoxia and the hypoxia-reoxygenation, whereas, the expressions of the iNOS and NFkappaB p65 proteins were not influenced. CONCLUSION: We concluded that hypoxia-reoxygenation induced the iNOS protein, and the subsequent production of NO in the VSMC. The antioxidants and the NOS inhibitor decreased the NO production during the hypoxia-reoxygenation, but did not affect the expressions of the iNOS and NFkappaB p65 proteins

Role of Inducible Nitric Oxide Synthase as a Mediator of Renal Ischemia/Reperfusion Injury in the Rat / 대한비뇨기과학회지

PURPOSE: This study was undertaken to elucidate if nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS) following renal ischemia/reperfusion (I/R), contributes to renal injury in rats, and if selective inhibition of iNOS prevents tissue injury following I/R. MATERIALS AND METHODS: Sprague-Dawley rats (male, 200-250gm, n=80) were divided into 4 groups. The groups were pretreated with L-arginine (L-ARG group), N-nitro-L- arginine methyl ester (L-NAME group), aminoguanidine (AG group) or normal saline (control group) before I/R. The renal blood flow was measured using laser Doppler at the left renal pedicle just before clamping the pedicle and at 15, 30, and 45 min after reperfusion. The HandE stain of nephrectomized tissues following I/R was performed for histological scoring of tubular damage and medullary vascular congestion. The expression of iNOS, using reverse transcription-polymerase chain reaction (RT-PCR), in the AG and control groups was determined in the kidney tissues following I/R. RESULTS: The recovery rate of the renal blood flow after I/R was significantly higher in the AG group compared to the controls. From light microscopy, the control group showed attenuated tubular lining epithelial cells, especially in the proximal tubules. However, Glomeruli and individual tubular cells showed no pathological changes. Mild congestion was noted in the medullary area. The L-NAME group showed marked tubular necrosis and medullary congestion. This tubular necrotic injury was compromised in the L-ARG group, but it was almost normal in the AG group. The medullary congestion was still severe in the L-ARG group, but was minimally present in the AG group. RT-PCR of the iNOS in the rat renal tissue revealed an iNOS band at 200bp. No significant difference in the density of the iNOS band was observed between the two groups. CONCLUSIONS: These results suggest that the NO, produced by iNOS following I/R, leads to renal tubular necrosis and medullary congestion, and selective inhibition of the iNOS may prevent renal tissue damage following I/R injury.

Effect of Guanylate Cyclase Inhibition on the Concentration of Nitrite in Culture Medium of Vascular Smooth Muscle Cell

PURPOSE: Nitric oxide (NO) exerts the relaxant effect in vascular smooth muscle cells (VSMC) by activating soluble guanylate cyclase (sGC), which produces cyclic guanidine monophosphate (cGMP) in the cell. This study was undertaken to investigate the mechanism of the inhibitory actions of sGC inhibitors, LY 83583 and methylene blue in the VSMC. METHODS: VSMC was primarily cultured from rat aorta and confirmed by immunocytochemistry of anti-smooth muscle myosin antibody. Bacterial lipopolysacchride (LPS), an inducer of inducible nitric oxide synthase (iNOS) and sodium nitroprusside (SNP), an NO donor, were uesd to increase NO within VSMC. The changes in concentrations of nitrite in culture media by an addition of LPS or SNP with a pretreatment of LY 83583 or methylene blue were measured by the spectrophotometry with griess regent and absorbance at 550 nm. Western blot and RT-PCR for iNOS and iNOS mRNA, respectively were performed. RESULTS: LPS and SNP increased nitrite concentration. LY 83583 potentiated the increase in nitrite concentration by LPS and SNP. LY 83583 also increased expressions of iNOS protein and mRNA induced by LPS. Methylene blue has no effect on nitrite concentration increased by LPS or SNP, and it did not affect the expressions of iNOS protein or mRNA induced by LPS. CONCLUSION: These results suggest that the mechanism of inhibitory actions of LY83583 and methylene blue on sGC are different each other: LY83583 interferes the interaction of sGC and NO resulting positive feedback increase in iNOS gene expression, but methylene blue eliminates NO from cytosol inducing no compensatory effect.

The Effects of Dexamethasone on Blood Pressure in Premature Infants with Bronchopulmonary Dysplasia

PURPOSE: To evaluate the effects of dexamethasone(D) on blood pressure(BP) in infants with bronchopulmonary dysplasia(BPD). METHODS: We retrospectively reviewed 10 infants with BPD(mean birth weight: 1,383+/-17 gm, mean gestational age: 29.0+/-1.7 weeks) treated with D at Wonkwang University Hospital from January 1994 to June 1998. D was started at 0.5 mg/kg/day intravenously for first week, followed by 0.3 and 0.1 mg/kg/day for second and third week, respectively. Changes in BP during pre-D, 1st wk(D1), 2ndwk(D2), 3rd wk(D3), and post-D periods were compared using Turkey Kramer multiple comparison test. RESULTS: Mean systolic pressure(sBP) significantly increased in Dl, D2, D3 compared to pre-D(63+1.3, P0.05). The sBP and dBP significantly increased from day 2 after initiation of D and were highest on day 17 and 17-18 of 3rd week, respectively. The number of hypertensive infants who were considered for antihypertensive medications were 2(20%) for sBP >or= 80-90 mmHg, 3(30%) for dBP >or= 50 mmHg and 1(10%) for dBP> or =60 mmHg. These infants, however, remained asymptomatic. CONCLUSION: Significant elevation of BP was observed during dexamethasone therapy for infants with BPD especially after 2nd day. However, BP elevation was transient, not requiring antihypertensive medications.