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Purpose@#The European Organization for Research and Treatment of Cancer quality of life (QOL) questionnaires (QLQ-C30, QLQ-OG25, and QLQ-STO22) are widely used for the assessment of gastric cancer patients. This study aimed to use these questionnaires to evaluate QOL in postgastrectomy patients. @*Methods@#We prospectively evaluated 106 patients with distal gastrectomy (DG), 57 with pylorus-preserving gastrectomy (PPG), and 117 with total gastrectomy (TG). Body weight and QOL questionnaires were evaluated preoperatively and postoperatively (at 3 weeks, and 3, 6, and 12 months). @*Results@#TG patients had significantly more weight loss than DG/PPG patients. Compared with DG, patients after PPG had less dyspnea (P = 0.008) and trouble with coughing (P = 0.049), but more severe symptoms of insomnia (P = 0.037) and reflux (P = 0.030) at postoperative 12 months. Compared with DG/PPG, TG was associated with worse body image, dysphagia, eating, and taste in both OG25 and STO22. Moreover, OG25 revealed worse QOL in the TG group with respect to odynophagia, eating with others, choked when swallowing, trouble talking, and weight loss. The QOL of patients who received chemotherapy was worse than those in the chemo-free group in both physical functioning and symptoms such as nausea/vomiting, appetite loss, and trouble with taste; however, these side effects would soon disappear after finishing chemotherapy. @*Conclusion@#PPG was similar to DG in terms of postoperative QOL and maintaining body weight, while TG was always inferior to both DG and PPG. Adjuvant chemotherapy can affect both body weight and QOL despite being reversible.
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Mesenchymal stem cell (MSC)-based therapy using gene delivery systems has been suggested for degenerative diseases. Although MSC-based clinical applications are effective and safe, the mode of action remains unclear. Researchers have commonly applied viral-based gene modification because this system has efficient vehicles. While viral transfection carries many risks, such as oncogenes and chromosomal integration, nonviral gene delivery techniques are less expensive, easier to handle, and safe, although they are less efficient. The electroporation method, which uses Nucleofection technology, provides critical opportunities for hard-to-transfect primary cell lines, including MSCs. Therefore, to improve the therapeutic efficacy using genetically modified MSCs, researchers must determine the optimal conditions for the introduction of the Nucleofection technique in MSCs. Here, we suggest optimal methods for gene modification in PD-MSCs using an electroporation gene delivery system for clinical application.
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Purpose@#To evaluate the feasibility and safety of intracorporeal overlapping gastrogastrostomy between the proximal anterior wall and antrum posterior wall (PAAP;PAAP anastomosis) of the stomach in minimally invasive pylorus-preserving gastrectomy (PPG) for early gastric cancer (EGC). @*Materials and Methods@#From December 2016 to December 2019, 17 patients underwent minimally invasive PPG with PAAP anastomosis for EGC in the high body and posterior wall of the stomach. Intraoperative gastroscopy was performed with the rotation maneuver during proximal transection. A longer antral cuff (>4–5 cm) was created for PAAP than for conventional PPG (≤3 cm) at the point where a safe distal margin and good vascular perfusion were secured. Because the posterior wall of the proximal remnant stomach was insufficient for intracorporeal anastomosis, the anterior wall was used to create an overlapping anastomosis with the posterior wall of the remnant antrum. The surgical and oncological outcomes were analyzed, and the stomach volume was measured in patients who completed the 6-month follow-up. The results were compared to those after conventional PPG (n=11 each). @*Results@#PAAP anastomosis was successfully performed in 17 patients. The proximal and distal resection margins were 2.4±1.9 cm and 4.0±2.6 cm, respectively. No postoperative complications were observed during the 1-year follow-up esophagogastroduodenoscopy (n=10). The postoperative remnant stomach (n=11) was significantly larger with PAAP than with conventional PPG (225.6±118.3 vs. 99.1±63.2 mL; P=0.001). The stomach length from the anastomosis to the pylorus was 4.9±2.4 cm after PAAP. @*Conclusions@#PAAP anastomosis is a feasible alternative for intracorporeal anastomosis in minimally invasive PPG for highly posteriorly located EGC.
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Purpose@#Quality of life (QOL) has become important in the trend of emphasizing patient satisfaction. This study aimed to evaluate the QOL in patients who underwent laparoscopic or robotic gastrectomy for gastric cancer. @*Methods@#A prospective trial was performed involving patients who underwent laparoscopic or robotic gastrectomy for primary gastric cancer at 11 hospitals in Korea. Within this comparative trial, QOL, postoperative pain, and long-term complications were exanimated. The quality-of-life questionnaire (QLQ)-C30 and QLQ-STO22 developed by the European Organization for Research and Treatment of Cancer were used for the QOL survey. We compared the data after dividing it into several types of characteristics as follows; device (robotic or laparoscopic), operation type, pathological stage, and sex.Biased components were extracted by logistic regression analysis. Propensity score matching was applied to the data set with the biased components. @*Results@#In total, 434 patients (211 for laparoscopic surgery and 223 for robotic surgery) were enrolled, out of which 321 patients who responded to both preoperative and postoperative surveys were selected for analysis. Robotic gastrectomy was not different from laparoscopic gastrectomy with respect to postoperative QOL. Distal gastrectomy showed better scores than total gastrectomy in terms of role functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, constipation, financial difficulties, dysphagia, eating restrictions, anxiety, taste, and body image. Male patients showed better scores on the 19 scales compared to female patients. @*Conclusion@#Robotic and laparoscopic approaches for gastric cancer surgery did not differ from each other with respect to QOL. Distal gastrectomy resulted in better QOL than total gastrectomy.
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Purpose@#The purpose of this study is to evaluate whether radiologic intervention in the pylorus decreases its function for delayed gastric emptying (DGE) patients after pylorus preserving gastrectomy (PPG) for gastric cancers and to determine the optimal interventional algorithm. @*Methods@#PPG patients who underwent intervention for DGE from January 2013 to December 2017 and a control group using propensity score matching were identified. Pyloric function was compared by subjective symptoms, postoperative upper gastrointestinal series at 3 months (short-term function), and esophagogastroduodenoscopy findings at 12 months (long-term function). Serum albumin levels and body weight change, 6 months and 12 months postoperatively, were compared to evaluate nutritional status. Interventional success rate, mean hospital stay, and recurrence of DGE were analyzed to determine the optimal intervention plan. @*Results@#Fifty-one out of 677 patients (7.53%) received intervention. There was no difference in pyloric function and nutritional status between the intervention and control groups. The interventional success rate for first-time balloon dilatation was 41.7% (20/48). If a second intervention was required and balloon dilatation was done, the success rate was 45.5% (5/11). However, if stent insertion was done, the success rate was 100% (17/17). Subsequent stent insertion after balloon dilatation resulted in a shorter mean hospital stay. Intervention including stent insertion had a lower recurrence of DGE than balloon only intervention (1.96% vs. 5.88%, P=0.041). @*Conclusion@#Radiologic intervention did not decrease long-term pyloric function. For treating DGE, if at first balloon dilatation fails, retrievable stent insertion can be considered as a second choice.
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Purpose@#The purpose of this study is to evaluate whether radiologic intervention in the pylorus decreases its function for delayed gastric emptying (DGE) patients after pylorus preserving gastrectomy (PPG) for gastric cancers and to determine the optimal interventional algorithm. @*Methods@#PPG patients who underwent intervention for DGE from January 2013 to December 2017 and a control group using propensity score matching were identified. Pyloric function was compared by subjective symptoms, postoperative upper gastrointestinal series at 3 months (short-term function), and esophagogastroduodenoscopy findings at 12 months (long-term function). Serum albumin levels and body weight change, 6 months and 12 months postoperatively, were compared to evaluate nutritional status. Interventional success rate, mean hospital stay, and recurrence of DGE were analyzed to determine the optimal intervention plan. @*Results@#Fifty-one out of 677 patients (7.53%) received intervention. There was no difference in pyloric function and nutritional status between the intervention and control groups. The interventional success rate for first-time balloon dilatation was 41.7% (20/48). If a second intervention was required and balloon dilatation was done, the success rate was 45.5% (5/11). However, if stent insertion was done, the success rate was 100% (17/17). Subsequent stent insertion after balloon dilatation resulted in a shorter mean hospital stay. Intervention including stent insertion had a lower recurrence of DGE than balloon only intervention (1.96% vs. 5.88%, P=0.041). @*Conclusion@#Radiologic intervention did not decrease long-term pyloric function. For treating DGE, if at first balloon dilatation fails, retrievable stent insertion can be considered as a second choice.
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PURPOSE@#To investigate whether there are specific surgical or clinical conditions where the use of autogenous bone (AB) is superior to the use of bone substitutes (BSs) for maxillary sinus floor augmentation (MSFA).@*MATERIALS AND METHODS@#We retrospectively analyzed 386 implants after MSFA in 178 patients. The implants were divided into five groups according to the sinus graft material used. Risk factors for implant failure in MSFA, and correlation between residual bone height (RBH) and graft materials in terms of implant survival were investigated. To investigate risk factors for implant failure in MSFA, implant survival according to graft materials, patients' sex/age, surgical site, RBH, healing period prior to prosthetic loading, staged- or simultaneous implantation with MSFA, the crown-to-implant ratio, prosthetic type, implant diameter, and opposite dentition were evaluated.RESULT: The cumulative 2- and 5-year survival rates of implants placed in the grafted sinus (independent of the graft material used) were 98.7% and 97.3%, respectively. None of the investigated variables were identified as significant risk factors for implant failure. There was also no statistical significance in implant survival between graft materials.@*CONCLUSION@#There were no specific surgical conditions in which AB was superior to BSs in terms of implant survival after MSFA.
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PURPOSE: Gastric cancer with lymph node metastasis (LNM) more than 15 (N3b) was defined as stage IV until the 6th AJCC system. However, it has been reclassified as a localized disease (stage IIb or III) since the 7th system. The aim of this study is to demonstrate that the survival of N3b is comparable to cytology-only positive (CY1-only) stage IV and to propose a new TNM system interpreting N3b as an eligibility criterion for receiving more intensive chemotherapy regimens. MATERIALS AND METHODS: 1,430 patients who underwent gastric cancer surgery at Seoul National University Hospital from 2007 to 2012 were retrospectively analyzed. The 5-year survival rate (5YSR) and 3-year recurrence-free survival (RFS) were evaluated according to the 7th and 8th systems, as well as a new categorization based on N-classification; N0-2 (LNM15). RESULTS: The survival of N3b is comparable to that of CY1-only stage IV (log rank test, P=0.671) and is distinct from that of grossly stage IV (log rank test, P<0.001). The survival of the remaining stage IIIc (T4bN3a) was comparable to those of N3b and CY1-only stage IV. Most N3b patients had significantly shorter 3-year RFS and mean RFS than those with IIb–IIIc, as if N3b itself was a higher TNM stage. CONCLUSIONS: In terms of survival, T4bN3a, N3b, and CY1-only stage IV were unified as stage IVa, while grossly stage IV was defined as stage IVb. N3b can be regarded as an eligibility criterion for undergoing more intensive chemotherapy regimens.
Subject(s)
Humans , Classification , Drug Therapy , Lymph Nodes , Neoplasm Metastasis , Retrospective Studies , Seoul , Stomach Neoplasms , Survival RateABSTRACT
The immunomodulatory effects of mesenchymal stem cells (MSCs) are an important mediator of their therapeutic effects in stem cell therapy and regenerative medicine. The regulation mechanism of MSCs is orchestrated by several factors in both intrinsic and extrinsic events. Recent studies have shown that the dynamic expression of cytokines secreted from MSCs control T cell function and maturation by regulating the expression of FoxP3, which figures prominently in T cell differentiation. However, there is no evidence that placenta-derived mesenchymal stem cells (PD-MSCs) have strong immunomodulatory effects on T cell function and maturation via FoxP3 expression. Therefore, we compared the expression of FoxP3 in activated T cells isolated from peripheral blood and co-cultured with PD-MSCs or bone marrow-derived mesenchymal stem cells (BM-MSCs) and analyzed their effect on T cell proliferation and cytokine profiles. Additionally, we verified the immunomodulatory function of PD-MSCs by siRNA-mediated silencing of FoxP3. MSCs, including PD-MSCs and BM-MSCs, promoted differentiation of naive peripheral blood T cells into CD4+CD25+FoxP3+ regulatory T (Treg) cells. Intriguingly, the population of CD4+CD25+FoxP3+ Treg cells co-cultured with PD-MSCs was significantly expanded in comparison to those co-cultured with BM-MSCs or WI38 cells (p < 0.05, p < 0.001). Dynamic expression patterns of several cytokines, including anti- and pro-inflammatory cytokines and members of the transforming growth factor-beta (TGF-β) family secreted from PD-MSCs according to FoxP3 expression were observed. The results suggest that PD-MSCs have an immunomodulatory effect on T cells by regulating FoxP3 expression.
Subject(s)
Humans , Cell Differentiation , Cell Proliferation , Cytokines , Mesenchymal Stem Cells , Regenerative Medicine , Stem Cells , T-Lymphocytes , T-Lymphocytes, Regulatory , Therapeutic UsesABSTRACT
PURPOSE: This study aimed to evaluate the clinical significance of microscopic invasion to determine the adequate resection margin in early gastric cancer (EGC). MATERIALS AND METHODS: A retrospective review was performed that included patients who underwent gastrectomy for clinical early gastric cancer (cEGC) at Seoul National University Hospital between January 2007 and December 2010. After subtracting the microscopic resection margin from the gross resection margin for each proximal or distal resection margin, microscopic invasion was represented by the larger value. Microscopic invasion and its risk factors were analyzed according to the clinicopathologic characteristics. RESULTS: In total, 861 patients were enrolled in the study. Microscopic invasion of cEGC was 6.0±12.8 mm, and the proportion of patients with microscopic invasion ≥0 mm was 78.4%. In the risk group, tumor location, pT stage, and differentiation did not significantly discriminate the presence of microscopic invasion. The microscopic invasion of EGC-IIb was 13.9±16.8 mm, which was significantly greater than that of EGC-I. No linear correlation was observed between the overall tumor size and microscopic invasion (R=0.030). The independent risk factors for microscopic invasion ≥20 mm were EGC-IIb vs. EGC-I/IIa/IIc/III (odds ratio [OR], 3.103; 95% confidence interval [CI], 1.533–6.282; P=0.002) and male vs. female sex (OR, 1.655; 95% CI, 1.012–2.705; P=0.045). CONCLUSIONS: Male sex and EGC-IIb were independent risk factors for microscopic invasion ≥20 mm. Examination of intraoperative frozen sections is highly recommended to avoid resection margin involvement, especially in cases of EGC-IIb.
Subject(s)
Female , Humans , Male , Frozen Sections , Gastrectomy , Retrospective Studies , Risk Factors , Seoul , Stomach NeoplasmsABSTRACT
OBJECTIVE: To investigate the relationship between glycosylated hemoglobin A (HbA1c) and complex regional pain syndrome (CRPS) in stroke patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective chart review was performed of stroke patients from January 2012 to December 2013. We reviewed 331 patients and included 200 in the analysis. We divided them into CRPS and non-CRPS groups and compared them by age, gender, stroke lesion, cause of stroke, duration of T2DM, HbA1c (%), National Institutes of Health Stroke Scale score, affected shoulder flexor muscle strength, Fugl-Meyer Assessment score, motricity index, Functional Independence Measure, Korean version of Modified Barthel Index, blood glucose level on admission day, duration from stroke onset to HbA1c check, and duration from stroke onset to three-phase bone scan for CRPS diagnosis. Thereafter, we classified the patients into five groups by HbA1c level (group 1, 5.0%–5.9%; group 2, 6.0%–6.9%; group 3, 7.0%–7.9%; group 4, 8.0%–8.9%; and group 5, 9.0%–9.9%) and we investigated the difference in CRPS prevalence between the two groups. RESULTS: Of the 200 patients, 108 were in the CRPS group and 92 were in the non-CRPS group. There were significant differences in HbA1c (p<0.05) between the two groups but no significant differences in any other factors. Across the five HbA1c groups, there were significant differences in CRPS prevalence (p<0.01); specifically, it increased as HbA1c increased. CONCLUSION: This study suggests that higher HbA1c relates to higher CRPS prevalence and thus that uncontrolled blood glucose can affect CRPS occurrence in stroke patients with diabetes.
Subject(s)
Humans , Blood Glucose , Complex Regional Pain Syndromes , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Diagnosis , Glycated Hemoglobin , Muscle Strength , Prevalence , Retrospective Studies , Shoulder , StrokeABSTRACT
BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). METHODS: The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. RESULTS: The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CONCLUSION: CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Subject(s)
Animals , Humans , Male , Rats , Angiogenic Proteins/genetics , Bile Ducts/surgery , C-Reactive Protein/analysis , Cells, Cultured , Disease Models, Animal , Hepatic Veins/abnormalities , Hepatocytes/cytology , Human Umbilical Vein Endothelial Cells , Lithocholic Acid/pharmacology , Liver/metabolism , Liver Cirrhosis/etiology , Liver Diseases/metabolism , Microscopy, Fluorescence , Mitochondria/drug effects , RNA Interference , RNA, Small Interfering/metabolism , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Serum Albumin/geneticsABSTRACT
OBJECTIVE: To evaluate the feasibility and effectiveness of a knee-ankle-foot orthosis powered by artificial pneumatic muscles (PKAFO). METHODS: Twenty-three hemiplegic patients (age, 59.6+/-13.7 years) were assessed 19.7+/-36.6 months after brain lesion. The 10-m walking time was measured as a gait parameter while the individual walked on a treadmill. Walking speed (m/s), step cycle (cycle/s), and step length (m) were also measured on a treadmill with and without PKAFO, and before and after gait training. Clinical parameters measured before and after gait training included Korean version of Modified Bathel Index (K-MBI), manual muscle test (MMT), and Modified Ashworth Scale (MAS) of hemiplegic ankle. Gait training comprised treadmill walking for 20 minutes, 5 days a week for 3 weeks at a comfortable speed. RESULTS: The 10-m walking time, walking speed, step length, and step cycle were significantly greater with PKAFO than without PKAFO, and after gait training (both p<0.05). K-MBI was improved after gait training (p<0.05), but MMT and MAS were not. CONCLUSION: PKAFO may improve gait function in hemiplegic patients. It can be a useful orthosis for gait training in hemiplegic patients.
Subject(s)
Humans , Ankle , Brain , Gait , Hemiplegia , Muscles , Orthotic Devices , Stroke , WalkingABSTRACT
BACKGROUND: Human chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from the placenta have been reported to demonstrate therapeutic effects in animal models of liver injury; however, the underlying epigenetic mechanism of this effect has not been elucidated. Thus, we investigated whether CP-MSCs influence epigenetic processes during regeneration of the injured liver. METHODS: CP-MSCs were engrafted into a carbon tetrachloride (CCl4)-injured rat model through direct transplantation into the liver (DTX), intrasplenic transplantation (STX), and intravenous transplantation via the tail vein (TTX). Non-transplanted (NTX) rats were maintained as sham controls. Liver tissues were analyzed after transplantation using immunohistochemistry, western blot analysis, and quantitative methylation-specific polymerase chain reaction. Proliferation and human interleukin-6 (hIL-6) enzyme-linked immunosorbent assays were performed using CCl4-treated hepatic cells that were co-cultured with CP-MSCs. RESULTS: The Ki67 labeling index, cell cyclins, albumin, IL-6, and gp130 levels were elevated in the CP-MSC transplantation groups. The concentration of hIL-6 in supernatants and the proliferation of CCl4-treated rat hepatic cells were enhanced by co-culturing with CP-MSCs (p<0.05), while the methylation of IL-6/IL-6R and STAT3 by CP-MSC transplantation decreased. CONCLUSION: These results suggest that administration of CP-MSCs promotes IL-6/STAT3 signaling by decreasing the methylation of the IL-6/SATA3 promoters and thus inducing the proliferation of hepatic cells in a CCl4-injured liver rat model. These data advance our understanding of the therapeutic mechanisms in injured livers, and can facilitate the development of cell-based therapies using placenta-derived stem cells.
Subject(s)
Animals , Humans , Rats , Blotting, Western , Carbon Tetrachloride , Chorion , Cyclins , DNA Methylation , Enzyme-Linked Immunosorbent Assay , Epigenesis, Genetic , Epigenomics , Hepatocytes , Immunohistochemistry , Interleukin-6 , Liver Regeneration , Liver , Mesenchymal Stem Cells , Methylation , Models, Animal , Placenta , Polymerase Chain Reaction , Regeneration , Stem Cells , VeinsABSTRACT
BACKGROUND: Acute liver failure (ALF) is a rapidly progressing and fatal disease for which liver transplantation (LT) is the only treatment. Posttransplant mechanical ventilation tends to be more prolonged in patients with ALF than in other LT patients. The present study examined the clinical effects of prolonged posttransplant mechanical ventilation (PMV), and identified risk factors for PMV following LT for ALF. METHODS: We reviewed data of patients undergoing LT for ALF between January 2005 and June 2011. After grouping patients according to administration of PMV (> or = 24 h), donor and recipient perioperative variables were compared between the groups with and without PMV. Potentially significant factors (P or = grade III), intraoperative blood pressure fluctuation, and oliguria (< 0.5 ml/kg/h) were independent risk factors for PMV. CONCLUSIONS: PMV was associated with deleterious outcomes. Besides care for known risk factors including hepatic encephalopathy, meticulous attention to managing intraoperative hemodynamic circulatory status is required to avoid PMV and improve the posttransplant prognosis in ALF patients.
Subject(s)
Humans , Blood Pressure , Hemodynamics , Hepatic Encephalopathy , Intensive Care Units , Liver , Liver Failure, Acute , Liver Transplantation , Logistic Models , Multivariate Analysis , Oliguria , Prognosis , Respiration, Artificial , Risk Factors , Tissue Donors , Vital SignsABSTRACT
OBJECTIVE: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. METHODS: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. RESULTS: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. CONCLUSION: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development.
Subject(s)
Female , Humans , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Matrix Metalloproteinase 9 , Norepinephrine , Norepinephrine Plasma Membrane Transport Proteins , Placenta , Placentation , Plasma , Pre-Eclampsia , Pregnant Women , RNA , RNA, Messenger , RNA, Small Interfering , Transfection , Trophoblasts , Up-RegulationABSTRACT
OBJECTIVE: This study was undertaken to determine the effect of hypoxia inducible factor (HIF)-1alpha on the cell death, autophagy, and invasion of trophoblasts. METHODS: To understand the effect of HIF-1alpha, we inhibited HIF-1alpha using siRNA under normoxia and hypoxia conditions. Invasion assay and zymography were performed to determine changes in the invasion ability of HIF-1alpha. Western blotting and immunofluorescence were performed to determine some of the signal events involved in apoptosis and autophagy. RESULTS: There was no difference in cell death through the inhibition of HIF-1alpha expression by siRNA; however, the expression of LC3 and autophagosome formation increased. On the other hand, autophagy was increased, and the invasive ability of trophoblast cells decreased according to the inhibition of HIF-1alpha expression by siRNA. These experimental results mean that HIF-1alpha genes regulate the invasive ability of trophoblasts by increasing autophagy. CONCLUSION: This study contributes important data for understanding the mechanism of early pregnancy implantation and the invasive ability of trophoblasts by defining the relationship between the roles of HIF-1alpha and autophagy.
Subject(s)
Pregnancy , Hypoxia , Apoptosis , Autophagy , Blotting, Western , Cell Death , Fluorescent Antibody Technique , Hand , Placenta , RNA, Small Interfering , TrophoblastsABSTRACT
BACKGROUND: Body posture, as a gravitational factor, has a clear impact on pulmonary ventilation and perfusion. In lung units with mismatched ventilation and perfusion, gas exchange and/or elimination of carbon dioxide can be impaired. In this situation, differences in the value of arterial and end-tidal carbon dioxide tension [Delta(PaCO2 - PETCO2)] are expected to increase. This study was conducted to observe how Delta(PaCO2 - PETCO2) changed according to the 3 different surgical positions, and to determine whether Delta(PaCO2 - PETCO2) is a reliable predictor of ventilation/perfusion mismatch when a patient is in different postural positions. METHODS: Fifty-nine patients were divided into either the chronic obstructive pulmonary disease (COPD) group (n = 29) or the non-COPD group (n = 30). PaCO2 and PETCO2 were measured during surgery in the supine, prone, and lateral decubitus positions after a 10 minute stabilization period. The Delta(PaCO2 - PETCO2) were calculated and compared among positions. RESULTS: The Delta(PaCO2 - PETCO2) decreased slightly in the prone position and increased significantly in the lateral decubitus position compared with the supine position in both groups. These patterns almost corresponded with the degree of ventilation/perfusion mismatch from the results of the radiological studies. The Delta(PaCO2 - PETCO2) in the COPD group was significantly greater than that in the non-COPD group at all surgical positions. CONCLUSIONS: Lateral decubitus position is associated with marked increase in Delta(PaCO2 - PETCO2), especially in patients with COPD. The Delta(PaCO2 - PETCO2) is a simple and reliable indicator to predict ventilation/perfusion mismatch at different surgical positions in patients with or without COPD.
Subject(s)
Humans , Benzeneacetamides , Carbon , Carbon Dioxide , Lung , Perfusion , Piperidones , Posture , Prone Position , Pulmonary Disease, Chronic Obstructive , Pulmonary Ventilation , Supine Position , Ventilation , Ventilation-Perfusion RatioABSTRACT
Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 microg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0 +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/- 9.5 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).
Subject(s)
Animals , Male , Rats , Analgesics/therapeutic use , Behavior, Animal/drug effects , Dexmedetomidine/therapeutic use , Disease Models, Animal , Hyperalgesia/chemically induced , Injections, Intraperitoneal , Pain Threshold , Rats, Sprague-Dawley , Vincristine/toxicityABSTRACT
Dexmedetomidine, which is a selective alpha2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 microg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 +/- 0.4, 9.1 +/- 1.9, 13.0 +/- 3.6, 16.6 +/- 2.4, and 24.4 +/- 1.6 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 +/- 4.2, 57.1 +/- 6.8, 34.3 +/- 5.7, 20.0 +/- 6.2, and 14.3 +/- 9.5 g at saline, 12.5, 25, 50, and 100 microg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).