Vascular Complications Related to Posterior Lumbar Disc Surgery

PURPOSE: To evaluate patients who underwent surgical or endovascular treatment after vascular injury related to posterior lumbar disc surgery. MATERIALS AND METHODS: We retrospectively reviewed seven cases of vascular injuries (four lacerations, one arteriovenous fistula [AVF], and two pseudoaneurysms) related to lumbar disc surgery by a posterior approach from January 1997 to December 2016 at Chonnam National University Hospital. Information of patient characteristics, diagnosis, treatment strategies, and outcomes were analyzed. RESULTS: Five out of seven cases were inhospital cases. In three laceration cases, each patient instantly became hypotensive and a life-threatening arterial injury was suspected. Therefore, the patient was immediately turned to the supine position and surgical repair was performed. The patients with pseudoaneurysm and AVF were treated by endovascular intervention. Remaining two were referred cases under the impression of vascular injuries. One laceration case of them was in preshock condition, and the left common iliac artery was surgically repaired. The other referred patient showed pseudoaneurysm which was treated with stent graft insertion. There was no surgery or endovascular intervention related death and none of the patients suffered any sequela related to vascular injury. CONCLUSION: Vascular injury associated with posterior lumbar disc surgery is not common, but can be fatal. Early recognition, diagnosis, and prompt treatment are essential to prevent fatal outcomes. Recently, endovascular intervention is increasingly and preferably used because of its low morbidity and mortality. However surgery is still the best option for the patients with unstable vital sign and endovascular approach can be applied to stable patients.

Vascular Injury in Posterior Lumbar Spinal Surgery / 대한정형외과학회잡지

Vascular complications are uncommon, but it may pose a serious problem in posterior spinal surgery. Vascular injury during lumbar spinal surgery should be suspected if symptoms of circulatory instability are noted. If vascular injury is suspected, a contrast enhanced computed tomography should be checked and proper management, i.e., interventional treatment or surgery should be performed. To date, there have only been a few reports regarding vascular injuries during posterior lumbar spinal surgery. Clinicians should pay attention to signs of vascular injury during posterior spinal surgery, and accordingly, promptly perform treatment. In two patients with retroperitoneal hemorrhage, extravasation of the common iliac arteries was successfully repaired. One patient with pseudoaneurysm was treated by stent placement.

Colon perforation due to embolization coil for internal iliac aneurysm

Coil migration is an extremely rare but hazardous complication of aneurysmal coil embolization. Only 1 case report has described coil migration following endovascular exclusion to gastrointestinal (GI) tract. We report the experience of a case of colon penetration caused by embolization coil placed for internal iliac aneurysm. A 66-year-old man visited the Emergency Department for hematochezia that had persisted for 3 months. Stent insertion and coil embolization of left internal iliac artery aneurysm had been performed on the patient 18 months ago. Colonoscopy was performed. It suggested penetration of sigmoid colon by embolization coil and diverticulum. Angiography revealed extravasation of contrast media at left internal iliac artery. Covered stent deployment was done in the left internal iliac artery. One week after the stent insertion, the patient underwent anterior resection, aneurysm resection, and coil removal. The patient recovered without complications. He was discharged at 2 weeks after the operation.

Alteration of Ankle-Brachial Index after Kidney Transplantation / 대한이식학회지

BACKGROUND: A steno-occlusive disease of the iliac artery can mimic renal vascular hypertension, and is an important cause of renal dysfunction in renal transplant recipients. We assessed the alternation of postanastomotic arterial blood flow of lower extremities by ankle-brachila index (ABI). METHODS: We analyzed 50 patients who underwent kidney transplantation between March, 2010 and November, 2012 at Chonnam National University Hospital. This study was performed prospectively and case selection by renal transplantation patients who got first operation on right iliac fossa. All operational procedures were end to side anastomosis of the external iliac artery to the renal artery. We measured and compared the preoperative and postoperative (1 week, 6 months, 1 year) ABI. We analyzed the diameter of the recipient external iliac artery and renal artery of the transplanted kidney. RESULTS: Among 50 patients, 34 were male (68%) and 16 were female (32%). The mean age of recipients was 44.37+/-11.42 years. The mean preoperative ABI at the right lower extremity was 1.17+/-0.11, postoperative 1 week, 6 months, and 1 year was 1.14+/-0.10, 1.15+/-0.11, 1.17+/-0.15, respectively. Alternation of preoperative ABI and postoperative 1 week, 6 months, and 1 year was P=0.331, P=0.864, and P=0.992, respectively. CONCLUSIONS: Alternation of ABI on the ipsilateral lower extremity was not significant in renal transplanted recipients. We recommend a long-term study with more cases.

Changes in suprarenal and infrarenal aortic angles after endovascular aneurysm repair

PURPOSE: We investigated whether suprarenal and infrarenal aortic angles change after the endovascular aneurysm repair (EVAR) procedure and during follow-up, and investigated the correlation between infrarenal aortic angle after EVAR and type Ia endoleaks. METHODS: Data collected on 70 EVAR procedures for a fusiform infrarenal aortic aneurysm performed between May 2006 and December 2012 were supplemented with a retrospective review of charts and radiographs. RESULTS: The greater the preoperative infrarenal aortic angle, the greater the suprarenal aortic angle (r = 0.72, P < 0.001). The infrarenal aortic angle decreased after the EVAR procedure and continued to decrease slowly thereafter (all P < 0.001). Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month (P < 0.001). No differences in angulation were observed based on stent graft type. Type Ia endoleaks occurred with significantly greater incidence in patients with a larger post EVAR infrarenal angle (P = 0.037). CONCLUSION: The infrarenal aortic angle decreased significantly immediately after the EVAR procedure and continued to decrease slowly thereafter. Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month. We found a correlation between infrarenal and suprarenal aortic angle. Type Ia endoleaks occurred with greater incidence in patients with a larger infrarenal angle immediately after EVAR.

Clinical Analysis of Foreign Bodies in Gastrointestinal Tract in Children / 소아외과

Foreign body ingestion is a common problem among paediatric populations. Most of the ingested foreign bodies spontaneously pass through the gastrointestinal tract, but approximately less then 10% of them remain without being discharged, and trigger complications. Therefore, proper evaluation and treatment according to the situation is required. In this study, clinical progress and complications were analyzed according to the clinical features and treatment in children who ingested foreign bodies. Among pediatric patients under 18 who were admitted to Chonnam National University Hospital after ingesting foreign bodies between January 2008 to June 2012, only the patients who had their foreign body in the gastrointestinal tract were included in this study. Based on medical records, age, type of foreign body, time spent till admission, and whether the endoscopy was done or not, complication were researched retrospectively. According to symptoms and plain abdomen X-ray findings, treatment was chosen and conducted among endoscopy, observation and emergency operation. Among 273 patients, 9 (3.3%) of them had surgical removal. Seven (2.6%) of them had an emergency operation on the day of admission, and the rest 2 (0.7%) had operation during observation. Removal through initial endoscopic approach was tried in 157 (57.5%) patients. Eleven (70.8%) of them had their foreign body removed at the initial trial, and 5 (4.9%) of them at the second trial. Among 109, who were on observation status, 9 (8.3%) of them needed endoscopic removal, and 2 (1.8%) of them suffered from surgical removal. It is thought to be better to approach slowly considering the type, size and symptoms in foreign body ingestion of pediatric patients, rather than immediate and invasive removal.

Factors Affecting the Endoleaks of Endovascular Aneurysm Repair in Infrarenal Abdominal Aortic Aneurysms / 대한혈관외과학회지

PURPOSE: The purpose of this study is to evaluate the factors affecting the endoleaks of endovascular aneurysm repairs in infrarenal abdominal aortic aneurysms. METHODS: On a retrospective basis, we analyzed 122 patients, who underwent endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm between March, 2006 and June, 2011. According to the endoleak, the patients were divided into 2 groups: endoleak group and non-endoleak group. We compared the following variables between the 2 groups: patient clinical characteristics (age, gender, body mass index, history of smoking, hypertension, diabetes mellitus, and coronary artery disease) and anatomical features of the aneurysms. RESULTS: A total of 111 male and 11 female patients were included. Fifty-two patients showed endoleak (42.6%) during follow-up periods (median: 4.6 years). There was no significant difference between endoleak and non-endoleak group according to patient's clinical characteristics and used devices. However, there were significant differences between two groups according to the anatomical features of the aneurysm, such as the morphology, size of the aneurysm, and the size and angle of the neck of the aneurysm. CONCLUSION: Endoleak indicated high frequency when the aneurysm size is large, and when the neck aneurysm is large, with the neck angle being more than 60 degrees. Thus, patients with more than one of the above three characteristics may need more attentive and cautious procedures as well as a closer follow-up.

MicroRNA profiling of tacrolimus-stimulated Jurkat human T lympocytes / 대한외과학회지

PURPOSE: This study investigated the Jurkat T cell line expresses cytotoxicity when treated with different concentrations of FK506, and analyzed the expression pattern of microRNA when stimulated by FK506 using the microRNAs microarray, as well as the expression pattern of a gene that is related to the differentiation, activation and proliferation of T cells after being affected by the change of microRNAs. METHODS: To investigate the effects of FK506 on microRNA expression, we purified total RNA of Jurkat cells treated with 20 microM FK506 for 72 hours and used to analyze microRNA profiling by using Agilent's chip. RESULTS: These results demonstrated that treatment with FK506 markedly induced the down-regulation of 20 microRNAs as well as the up-regulation of 20 microRNAs in a time-dependent manner. The genes that down-regulated by FK506 include let-7a*, miR-20a*, and miR-487a. Otherwise miR-202, miR-485-5p, and miR-518c* are gradually up-regulated in expression. Sanger Institute and DAVIDs bioinformatics indicated that microRNAs regulated the several transcriptomes including nuclear factor of activated T cell-related, T cell receptor/interleukin-2 signaling, and Ca(2+)-calmodulin-dependent phosphatase calcineurin pathways. CONCLUSION: As a result of treating FK506 to a Jurkat cell line and running the microRNA microarray, it was found that FK506 not only took part in the suppression of T cell proliferation/activation by inhibiting calcineurin in Jurkat apoptosis, but also affected the microRNAs that are involved in the regulation of various signal transduction pathways.

Evaluation of the Korean Network for Organ Sharing Expanded Donor Criteria in Deceased Donor Renal Transplantation / 대한이식학회지

BACKGROUND: This study was conducted in order to evaluate the propriety of expanded donor criteria in Korea and to identify the preoperative factors influencing allograft survival and function. METHODS: We studied 404 patients who received deceased renal transplants from five transplantation centers of 2, 3 territory from 2000 to 2010. Differences in 1-year graft function, delayed graft function (DGF) rate, and graft survival rate between the standard criteria donor (SCD) and expanded criteria donor (ECD) were compared retrospectively. The preoperative factors influencing graft function and graft survival were analysed. RESULTS: SCD showed significantly better 1-year graft function than ECD (P=0.011). No differences in 1-year acute rejection rate were observed between SCD (13.2%) and ECD (16.9%) (P=0.449). Significantly higher DGF rate was observed for ECD (25.4%) than for SCD (14.1%) (P=0.022). Graft type had no significant influence on 5-year graft survival (SCD 94.5% vs. ECD 93.7%) (P =0.835). Advanced donor age (P=0.001), donor hypertension history (P=0.047), high serum creatinine (P=0.002), and cerebral infarction as cause of death (P=0.004) had a negative influence on 1-year allograft function. Significantly low graft survival was observed for advanced donor age (P =0.002). CONCLUSIONS: Graft function, DGF rates of ECD were poorer than those of SCD. Graft survival rate of ECD was comparable to that of SCD kidney. Korean Network for Organ Sharing expanded criteria may underestimate the organ quality of deceased kidney and modification may be needed in order to expand the potential donor pool through nationwide study.

Clinical Experiences of Transarterial Embolization after Abdominal Surgery in Trauma Patients / 대한혈관외과학회지

PURPOSE: Transarterial embolization has been known as an effective nonsurgical treatment for selected patients with intraabdominal hemorrhage. This study was conducted to evaluate the clinical outcomes of transarterial embolization after emergency operation in the blunt abdominal trauma patients with hemoperitoneum. METHODS: Between January 2004 and December 2008, a total of 13 consecutive blunt abdominal trauma patients with intraabdominal hemorrhage who received transarterial embolization after abdominal surgery were included. The characteristics, procedures, and the clinical outcomes of patients were analyzed, retrospectively. RESULTS: There were 6 males and 7 females. Age ranged between 21 and 77 years (mean 42.3 years). The most common injured organ was the liver (10 patients, 76.9%), and the most common embolized artery was hepatic artery (8 patients, 61.5%). Transarterial embolizations were intended to control the continued bleeding (9 patients, 69.2%), delayed bleeding (3 patients), and arteriovenous fistula (1 patient). Further, technical success was achieved in all 13 patients. One of 13 patients died of multiorgan failure. No procedure-related complications were observed. CONCLUSION: Angiography has a high detection rate of bleeding sites in patients with intraabdominal hemorrhage after blunt abdominal trauma. Transarterial embolization is considered as an effective and safe method in the management of intraabdominal hemorrhage after abdominal surgery in trauma patients.

Long Term Outcomes for Living Renal Donors / 대한이식학회지

BACKGROUND: Kidney donation is a relatively safe procedure with minimal adverse effects. But some reports have described the development of proteinuria and hypertension in donors after nephrectomy. There have been a number of non-Korean studies which conclude that the procedure is relatively safe and a good quality of life is expected for living donors after kidney transplantation, but not enough of these studies have been published in Korea. We evaluated the physiologic and psychosocial impacts after kidney donation in this study. METHODS: Between April 1988 and April 2010, we performed 201 living donor nephrectomies and obtained information for 88 (43.7%) of the donors. We measured their estimated glomerular filtration rate (GFR), blood pressure, body mass index, hemoglobin and cholesterol level, and assessed the prevalence of hypertension and proteinuria in this group. These donors completed a questionnaire regarding their health status and psychosocial outcomes after donation. RESULTS: The average time of the donor assessment after nephrectomy was 95.05+/-85.45 months (range, 6~261). The left kidney was used in 76 patients (86%). There was a total complication rate of 8%, but no serious complications were observed. Proteinuria was found in 9 patients (10%) and hypertension in 11 patients (11%). GFR decreased from 103.65+/-25.02 mL/min to 76.12+/-19.90 mL/min (P<0.001) and hemoglobin decreased from 13.91+/-1.62 g/dL to 13.01+/-1.72 g/dL (P<0.001). Five patients (6%) developed a post-donation GFR between 40 and 60 mL/min, with 2 patients being observed to have a post-donation GFR below 20 mL/min. In the questionnaire responses, most donors did not report problems affecting routine life or any economic impact. Their donation satisfaction results were very high (92%). CONCLUSIONS: Living kidney donors were observed to result in reduced GFR after nephrectomy. Follow-up visits with living kidney donors is essential in order to monitor risk factors related to the deterioration of their residual kidney function.

Mycophenolic acid mediated mitochondrial membrane potential transition change lead to T lymphocyte apoptosis / 대한외과학회지

PURPOSE: This study demonstrated that apoptosis induced by mycophenolic acid (MPA) is mediated by mitochondrial membrane potential transition (MPT) changes in Jurkat cells. METHODS: Cell viability and MPT changes were measured by flow cytometry. Western blotting was performed to evaluate the expression of Bcl-2 family proteins, Bid, truncated Bid (tBid), cytochrome c, voltage dependent anion channel (VDAC), poly ADP-ribose polymerase (PARP), and protein kinase C-delta (PKC-delta). The catalytic activity of caspase-9 and -3 was also measured. RESULTS: Cell viability was decreased in time- and dose-dependent manners. Bcl-2 protein expression was decreased, but Bax protein expression was identified. A decreased Bcl-XL /Bcl-XS ratio was also noted. The expression of tBid protein also increased in a time-dependent manner in Jurkat cells treated with MPA. While normal MPT appeared as orange fluorescence, abnormal MPT corresponded to green fluorescence. Green fluorescence increased as orange decreased in the MPA-treated cells. Significantly increased concentrations of MPA induced the release of cytosolic cytochrome c. MPA also augmented the catalytic activity of caspase-9 and caspase-3 in Jurkat cells. Our findings demonstrated that MPA-induced apoptosis is mediated by MPT changes accompanied by decreased Bcl-XL expression and the appearance of tBid protein. The release of cytosolic cytochrome c from mitochondria and increased catalytic activity of caspase-9 and caspase-3 were observed in MPA-treated Jurkat cells. CONCLUSION: These results suggest that mitochondrial dysfunction caused by MPA induces human T lymphocyte apoptosis.

Clinical Implications of Multiple Endovascular Treatments for Patients with Lower Limb Deep Vein Thrombosis

PURPOSE: The aim of this study is to assess the clinical benefits of endovascular treatment for lower extremity deep vein thrombosis. Particularly, we wanted to define the factors that affect the recurrence of deep vein thrombosis (DVT) after repeated endovascular treatments. METHODS: Eighty six patients who were diagnosed with DVT from January 2003 to December 2008 were retrospectively examined. All the patients were diagnosed by lower extremity computed tomography scanning. Multimodality therapy was performed to achieve primary venous patency. The multimodality strategy included catheter-directed thrombolysis followed by percutaneous transluminal balloon angioplasty and stenting for any residual stenosis. RESULTS: Fifteen patients (17%) underwent repeated endovascular treatment. The onset of symptoms and a history of DVT were the factors that affected the recurrence of DVT. Repeated endovascular treatment showed considerably significant differences for recurrence between the single and multiple groups (28/71 [39.6%] vs. 9/15, respectively, [60%]) and for the mean venous patency duration (29.1 months [confidence interval (CI), 22.6~35.7] vs. 12.4 months, respectively, [CI, 6.7~20.2]) (P=0.001). CONCLUSION: Although multiple endovascular treatment demonstrated a favorable primary outcome, there were no definite benefits of multiple endovascular treatment on the long term follow-up. In the subgroup that has focal remnant thrombus, one more additional endovascular treatments would benefit for the recurred lower extremity deep vein thrombosis.

Indirect Inguinal Hernia in Pediatric Patients

Herniorrhaphy of Indirect inguinal hernia (IIH) is one of the most frequently performed surgical procedures in children. The overall incidence of inguinal hernias in childhood ranges from 0.8 to 4.4%. The incidence is up to 10 times higher in boys than girls, especially much higher in premature infants. IIHs in children are basically an arrest of embryologic development rather than an acquired weakness, which explains the increased incidence in premature infants. In normal development, the processus vaginalis closes, obliterating the peritoneal opening of the internal ring between 36th and 40th week of gestation. This process is often incomplete, leaving a small patent processus in many newborns. However, closure continues postnatally, and the rate of patency is inversely proportional to age of the child. The presence of a patent processus vaginalis is a necessary but not sufficient variable in developing a congenital IIH. In other words, all congenital IIHs are preceded by a patent processus vaginalis, but not all patent processus vaginalis go on to become IIHs. The overall incidence of IIH in population is approximately 1 to 2% and the incidence of a processus vaginalis is approximately 12 to 14%, clinically appreciable IIH should develop in approximately 8 to 12% of patients with a patent processus vaginalis. Although the classic open inguinal hernia repair remains the gold standard for most pediatric surgeons, laparoscopic repair is being performed in many centers. Like open technique, laparoscopic technique is fundamentally a high ligation of the indirect hernia sac with or without internal ring ligation. The advantages of laparoscopic approach include the ease of examining the contralateral internal ring, the avoidance of access damage to vas and vessels during mobilization of cord, decreased operative time, and an ability to identify unsuspected direct or femoral hernias. Almost all groin hernias in children are IIHs and occur as a result of incomplete closure of processus vaginalis. The treatment is repair by high ligation of hernia sac, which can be done by an open or laparoscopic technique. The contralateral side can be explored by laparoscopy or left alone, open exploration is no longer indicated due to potential risk of infertility.

Perivascular epithelioid cell tumor (PEComa) of the ascending colon: the implication of IFN-alpha2b treatment / 소아과

A 7-year-old boy presented with hematochezia and abdominal pain. A 3.7-cm-sized mass was identified in the ascending colon by abdominal computed tomography and colonoscopy. The patient underwent surgical resection. Pathological examination revealed a low-grade perivascular epithelioid cell tumor (PEComa). PEComa in the colon is very rare. Only a few cases have been reported so far. An effective treatment method for this rare tumor has not been established yet. The patient received adjuvant interferon-alpha immunotherapy for 1 year. He has been tumor-free for 26 months since the initial diagnosis. This report is the first documented case of the use of interferon-alpha for pediatric PEComa of the colon.

A Proposal to Activate Organ Donation: Report of Organ Allocation Study Group / 대한이식학회지

Organ shortage is a serious problem in the field of solid organ transplantation. Increasing number of death on the waiting list, transplant tourism, black market for organ selling are all caused by organ shortage and these eventually causing poor quality of life for patient and family, and may give rise to a serious confusion in domestic transplant system. Since the KONOS launched in the year 2000, some portion of the illegal side of organ supply were corrected but the number of organ donor was hardly to increase. In order to search any solution for this problem, organ allocation study group under the Korean society for organ transplantation was actively worked from August 2008 through February 2009, and got some solution. Among them, amendment of the transplantation law including brain death committee, reporting system of suspected brain dead patients, and set up an independent organ procurement organization system for an effective organ procurement. Organ donation and increasing the number of donor is not a task only for transplant society, but is closely related with quality of life for peoples. This also can change the execution of budget of national medical health insurance. To give a correct understanding about this and activate the nationwide organ donation, the transplant society should have a key role with various medical and nursing society, hospital association, government, national assembly and every voluntary groups.

Apoptosis Gene Expression Pattern Analysis of Jurkat Cells Treated with FK506

PURPOSE: FK506 (tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. Previously FK506 was known to cause apoptotic death of human Jurkat T cells. METHODS: The current study was designed to analyze the gene expression pattern of Jurkat T cells after FK506 application by using cDNA microarray. Treatment of Jurkat T cells with FK506 resulted in a decrease of cell viability in a time- and dose-dependent manner. Next, total RNA of Jurkat T cells was extracted by using TRIzol reagent and used to carry out a confirmation test for the purity and integrity of total RNA. RESULTS: Gene expression levels related to apoptosis and cell cycle process were mainly focused to analyze in FK506-treated Jurkat T cells. According to the inhibition of calcineurin activity, MARCKS in PKC substrates and Sp3 transcription factor was markedly increased in FK506-treated cells. Also, cell cycle control gene Id1 and Id3 were induced in expression from FK506-treated Jurkat T cells. However, FK506 decreased the expression of Src homology 2, G protein, and MEK 2 genes in bioactive peptide induced signaling pathway. It also reduced the expression level of the insulin receptor, DRPLA and Bai1-associated protein 2 genes, which are involved in the regulation of cell motility and morphology control. CONCLUSION: The author will continue to pursue the exact functional roles of genes that are markedly changed in expression by FK506 in human Jurkat T cells in vitro and in vivo experimental models.

The Effect of FK506 to Generate Reactive Oxygen Species on T Lymphocyte Death

PURPOSE: Tacrolimus (FK506) has been widely used as an immunosuppressant in organ transplanted recipients to suppress organ rejection phenomenon. We investigated the role of oxidative stress and heme oxygense-1 by FK506 on human Jurkat T cells. METHODS: The cells viability was examined by DAPI stain, enzyme activity of caspase family proteins, and western blotting for Baks, PUMA, iNOS, HO-1. Cells were cultured in the absence or presence of CoPPIX or ZnPPIX and the fluorescence intensity was analyzed using a flow cytometry. RESULTS: Treatment with FK506 increased the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, and NO in Jurkat cells in a dose-dependent manner. Immunohistochemistry and Western blot analysis data revealed the hemoxygenase-1 (HO-1) was induced by the addition of FK506 in Jurkat cells. Induction of CoPP, HO-1 inducer, resulted in decreased intracellular H2O2 and NO concentrations. Instead ZnPP, an HO-1 competitive inhibitor did it reversely. In addition, ZnPP regulates iNOS protein synthesis by inhibition of HO-1. CONCLUSION: Increase of HO-1 expression would induce to decrease the intracellular H2O2 and NO concentrations. Also, HO-1 would regulate iNOS protein synthesis. Consequently, we can expect the regulation of HO-1 expression with concomitants use of FK506 to suppress organ rejection phenomenon by enhancing apoptosis.

Mycophenolic Acid Induced Apoptosis in Human Jurkat Cells viathe Generation of Reactive Oxygen Species

PURPOSE: Mycophenolic acid (MPA) is the active agent of mycophenolate mofetil (MMF), which is an immunosuppressive drug. MPA is a selective inhibitor of inosine monophosphate dehydrogenase. The aim of this study was for demonstrate that mycophenolic acid induces apoptosis in human Jurkat cells via the generation of reactive oxygen species (ROS). METHODS: The cells were cultured in the presence or absence of MPA. Flow cytometric analysis was performed after propidium iodide staining. Western blotting for caspase 3, Bcl-2 and Bax proteins was also performed. RESULTS: MPA decreased the viability of Jurkat cells in a dose- and time-dependent manner. The MPA induced apoptotic cell death displayed nuclear fragmentation and sub G0/G1 phase arrest in the Jurkat cells. The expression of caspase-3 proteases in the MPA treated-Jurkat cells increased in a time-dependent manner. Treatment with MPA resulted in increased ROS generation in the Jurkat cells. There was a decreased expression of Bcl-2 and an increased expression of Bax protein in the MPA treated Jurkat cells. CONCLUSION: This result suggests that MPA-induced cytotoxicity is associated with a direct increase of both ROS generation and the expression of Bax protein.

Effect of Rapamycin on the Cell Cycle Arrest of T Lymphocytes

PURPOSE: Rapamycin (RPM) and its analogues are known for their potent immunosuppressant and anti-proliferative properties, which stem from their ability to modulate the signal transduction pathways involved in cell cycle progression from the G1 to S phase. Thus, RPM has been shown to inhibit the proliferation of a number of non-immune cell types, including hepatocytes, vascular smooth cells and fibroblasts. In addition to its effects on proliferation, RPM may also play a role in the regulation of apoptosis under certain circumstances. METHODS: The effects of RPM on the activation, proliferation and expression of cytotoxic effector molecules were examined on Molt-4 human T-lymphocyte by determining its effects on apoptosis, cell viability, reactive oxygen species (ROS) production and mitochondrial dysfunction. Cells were cultured in the presence or absence of RPM, and then analyzed by Flow cytometry after staining with PI (propidium iodide). RESULTS: The viability of Molt-4 T cells dose- and time-dependently decreased on the addition of RPM. CONCLUSION: RPM induced cytotoxicity was characterized by G2/M phase cell cycle arrest. In addition, a pharmacological scavenging study of ROS, including H2O2, revealed the cytotoxicity was mainly induced by the generation of ROS, which might modulate the expression of Bak protein and mitochondrial dysfunction.