TEHRAN UNIVERSITY MEDICAL JOURNAL (TUMJ)
Year:2014 | Volume:72 | Issue:7|Papers Count:14

Differentiated cells can change to embryonic stem cells by reprograming. Generation of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative and personalized medicine. iPSCs can self-renew and differentiate into many cell types. iPSC cells offer a potentially unlimited source for targeted differentiation. Through the expression of a set of transcription factors, iPSCs can be generated from different kinds of embryonic and adult cells. This technology for the first time enabled the researchers to take differentiated cells from an individual, and convert them to another cell type of interest, which is particularly to that person. When the set of master transcription factors containing OCT4, SOX2, KLF4, and MYC is expressed ectopically in somatic cells, the transcriptional network is propelled to organize itself in such a way as to maintenance a pluripotent state. Since iPSCs are similar to Embryonic Stem Cell (ESC), they can be considered as sources for modeling different diseases. iPSCs which are induced from somatic cells of patient can be useful for screening and drugs selection, and also introduce treatment via grafting the cells. Although this technology has been successful in different fields, the tumorigenesis of viral vectors during induction of reprogramming is a major challenge. Nevertheless, iPSCs are valuable for clinical applications and research. By discovery of these cells many challenges related to the safety, efficacy, and bioethics of ESCs are solved. Pluripotency is defined in two aspect of functional and molecular, by which functional regards the capacity of cell is generate three kinds of embryonic layers and germ line, and molecular aspect regards the identifying of molecules and genes that support functional features. Identification of these genes has been placed at the center of fields related to development and stem cell research. In this review, we discuss the process of generation of these cells, as well as required genes and factors for pluripotency, and also current progress in generation of iPSCs utilizing tens of reliable and new studies.

Background: Controlling parenchymal hemorrhage especially in liver parenchyma, despite all the progress in surgical science, is still one of the challenges surgeons face saving patients’ lives and there is a research challenge among researchers in this field to introduce a more effective method. This study attempts to determine the haemostatic effect of aluminum chloride and compare it with that of the standard method (simple suturing technique) in controlling bleeding from liver parenchymal tissue.Methods: This is an experimental study. In this animal model study 60 male Wistar rats were randomly allocated into six groups and each of which contains 10 mouse. An incision, two centimeters (cm) long and half a cm deep, was made on each rat’s liver and the hemostasis time was measured once using aluminum chloride with different concentrations (5%, 10%, 15%, 25%, and 50%) and then using the control method (i.e. controlling bleeding by simple suturing). The liver tissue was examined for pathological changes. Finally, the obtained data were entered into SPSS software and analyzed using Kruskal- wallis test, Mann- Whitney, Kolmogorov- Smirnov test. Results: The mean time to hemostasis in groups of aluminum chloride concentration of 50%, 25%, 15%, 10% and 5% were respectively, 8.90, 13.10, 23.30, 30.30 and 37.8 seconds, also in the control group (suture) mean time of hemostasis was 60/81 seconds. The haemostatic times of different concentrations of aluminum chloride were significantly less than that of the control group (P<0.001). There was a statistically significant difference between every two haemostatic times (P<0.001). The pathologic examination showed the highest frequency of low grade inflammation based on the defined pathological grading.Conclusion: Aluminum chloride compare to the control method (i.e. controlling liver bleeding by simple suturing) needs less time to control liver bleeding. Aluminum chloride is an effective agent in controlling liver hemorrhage in an animal model.

Background: Colorectal cancer is a major cause of morbidity and mortality throughout the world, and its treatments include surgery, chemo-radiotherapy. Despite improvements in clinical outcomes of patients with this tumor over the past decades, prognosis remains poor with a 5-year survival rate of <10%. Angiogenesis inhibitor agents have been recently added to the treatment regimen of this disease. In the past two decades, it has been recognized that selective inhibitors of the cyclooxygenase -2 (Cox-2) enzyme result in the regression in the size of colorectal tumor, and one of its reasons is attributed to angiogenesis inhibition. The present study aimed at identifying the molecular pathways of angiogenesis inhibition by celecoxib.Methods: HCT-116, which is one of the cell lines of Colorectal cancer (separated from human colorectal adenocarcinoma) was provided by the National Cell bank of Iran (NCBI) affiliated to Pasteur Institute. It was then cultured in DMEM (high glucose) culture medium containing 10% FBS, and then treated in the active substance of celecoxib at pharmacological concentrations of 50 mM (C50) and 100 mM (C100). Afterwards, RNA was extracted and cDNA was prepared. The oligonucleotide of HIF-1 Alpha gene (angiogenesis initiator) was prepared and the level of HIF-1 alpha gene expression was assessed with a real-time PCR device in three control, C50 and C100 groups.Results: HIF-1 alpha gene expression significantly decreased in the celecoxib treatment group (compared with control group) with the concentration of C100 (P<0.001), but no change was observed in the concentration of C50.Conclusion: Angiogenesis is a key factor in the carcinogenesis process and FDA today approved bevacizumab as a first-line treatment for patients with metastatic colorectal cancer. The results of this study showed one of the causes of angiogenesis reduction in celecoxib-treated colorectal cancer. According to clinical findings and basic studies, celecoxib will be hopefully used as a first-line therapy along with chemotherapy in the near future in colorectal cancer. The advantages of this treatment method include its low cost and low side effects.

Background: Recently, bone-marrow-derived cells have introduced new therapeutic approaches to the management of wound healing in severe skin injuries. Bone marrow-derived stromal cells are described as a heterogeneous population, including mesenchymal stem cells, hematopoietic stem cells, and fibro-blast cells. Results derived from several studies indicate that these cells may contribute to tissue regeneration whether through producing variety of bioactive growth factors and/or by differentiation into mesoderm lineage. The aim of the present study was to investigate the effect of subcutaneous administration of bone marrow-derived stromal cells in repairing or regeneration of skin wounds induced by third-degree burn in a mouse model.Methods: In an experimental study that was performed in Urmia University research center from December 2011 to June 2012, The third-degree skin burn was induced on the shaved backs of healthy 7-8 week old male mice (N=18) using a metal rods heated in boiling water. After 1 hour, based on the equal physical condition mice were randomly divided into two separate groups and then subcutaneously administered with phosphate buffered saline (PBS; 400 ml) or bone marrow-derived stromal cells (106 cell in 400µl PBS) at the burn site. 7, 14 and 21 days after induction of burn injury, biopsies were taken from burn wounds and then the sections were prepared. Subsequently the prepared sections were stained with hematoxylin/eosin and Masson's trichrome to explore histopathological changes evoke by administration of bone marrow derived stromal cells in comparison with control subjects.Results: Considering investigated parameters including formation of granulation tissue (respectively on days 7, 14 and 21 P≤0.007, P≤0.0013 and P≤0.001), angiogenesis (on day 21 P≤0.002) and collagen deposition, in mice treated with bone marrow-derived stromal cells the rate of healing of third-degree thermal burns was significantly accelerated when compared to the PBS-treated mice.Conclusion: This experimental modulation of wound healing suggests that bone marrow-derived stromal cells can significantly enhance the rate of wound healing possibly through stimulation of granulation tissue, angiogenesis, fibroblast proliferation and collagen deposition.

Background: Previous investigations have shown that pregnancy-associated plasma protein-A (PAPP-A) levels are associated with adverse pregnancy outcomes including intrauterine growth restriction (IUGR) fetuses as well as preterm delivery. The aim of this study was to determine the rate of preterm delivery in women with low PAPP-A and at intermediate risk for chromosomal abnormalities in the first trimester screening.Methods: A total of 137 women who underwent Down syndrome screening between 11 to 14 weeks of gestation were studied from September 2011 to September 2013 at Perinatal Care Clinic, Imam Khomeini Hospital, Ahvaz, Iran. From those, 52 patients had low PAPP-A. Inclusion criteria were singleton pregnancies, at 11 to 14 weeks of gestation, at intermediate risk for Down syndrome (risk in 1:101 to 1:1000). The intermediate risk was estimated based on maternal parameters, maternal serum markers (PAPP-A and b-hcG), and nuchal translucency (NT) using fetal medicine foundation (FMF), UK) software. The power of the study was 90%. The sample size was estimated based on prevalence of preterm delivery in pregnancies with low PAPP-A in the first trimester screening. Patients were followed-up until delivery to observe pregnancy outcomes. We evaluated the variables such as level of PAPP-A, outcomes of delivery, age, b-hCG, and gestational age.Results: Among 137 normotensive pregnant women at intermediate risk for Down syndrome, 52 cases (38%) had low PAPP-A (<0.4 MoM). Of 52, 14 cases (27%) had preterm delivery. None of our patients had pregnancy related or non related diabetes, preeclampsia, or chromosomal anomalies. 45 cases (86%) from 52 patients were equal or less than 35 years, while 7 patients were more than 35 years. Among 52 followed-up patients, 48 patients (92.4%) were at low-intermediate risk (risk in 1:251 to 1:1000), and 4 cases (7.6%) were at high-intermediate risk (risk in 1:101 to 1:250).Conclusion: We found high frequency of preterm delivery in pregnant women with low PAPP-A level at the first trimester screening. Hence, this group of patients needs special and early preventive management. Furthermore, we suggest that future researches to be conducted with larger sample size and also cervix length measurement to be included.

Pleural effusion (PE) is common among ICU and acutely ill patients. Traditionally plain chest radiography (CXR) has been done for pleural effusion evaluation in ICU. However, better results have been reported by ultrasound for the diagnosis of this condition in ICU. In this study, we compared two methods of ultrasound and CXR in PE detection in ICU patients. Also we studied the percentage of thoracentesis by physician after detection of PE by ultrasonography or CXR.Methods: Portable supine CXR and chest ultrasound were done in Thirty-nine non-surgical patients who were admitted to the Medical and General ICUs of Imam Khomeini hospital in Tehran from Oct 2013 to Mar 2014. Ultrasound was done and interpreted by radiologist and CXR by patient physician. Thoracentesis or CT-scan was used as gold standard for PE diagnosis.Results: Ultrasound in 29 patients (74.3%) showed PE. In 21 patients thoracentesis was done by patient’s physician and all had PE with mean volume of 447.2(417.6). In 13 of 18 patients without thoracentesis chest CT scan was available. It shows PE in 6 cases (all with positive PE in ultrasonography). CXR in 9 patients (23.1%) was positive for PE and in 30 patients (76.9%) was negative. The ability of chest ultrasound and CXR for diagnosis of PE was significantly different (P= 0.0.1). In 68.9 % of cases that ultrasound was positive, the CXR was negative and only in 34.5% of cases both methods had negative results. The sensitivity, specificity, positive and negative predictive values were 100% (87.1-100), 100% (58.9-100), 100% (87.1-100), 100% (58.9-100) respectively for ultrasonography. For CXR there were 33% (16.6-54.0), 100% (58.9-100), 100% (66.2-100), 28% (12.1-49.4) respectively.Conclusion: Ultrasonography for diagnosis of pleural effusion in ICU patients has better diagnostic performance than portable CXR.

Background: Morbid obesity is associated with a some of significant comorbidities. Early and uneventful postoperative recovery of obese patients remains a challenge for anesthesiologists. It seems Bispecteral Index (BIS) monitoring may reduce drug usage and hasten recovery time in inhalation anesthesia. The aim of this study was to investigate the effect of BIS monitoring on intraoperative isoflurane utilization and the early recovery profile.Methods: Fifty morbidly obese adult patients (Body Mass Index (BMI) of 35 kg/m2 or grater) undergoing elective laparoscopic cholecystectomy in Urmia Imam Khomeini Hospital were enrolled in this prospective, Cohort and single blind study. Duration of this study was six months between April to September 2012. Patients were randomly divided two groups (25 patients per group). In the first phase of the study, patients were anesthetized without the use of BIS monitoring and isoflurane being administered according to standard clinical practice (this group formed the control group). In a second phase, with use of BIS monitoring isoflurane was titrated to maintain a BIS value between 40 and 60 during surgery, and then 60-70 during 15 min before the end of surgery (this group formed the BIS group). Isoflurane consumption and recovery time were compared between two groups.Results: All patients completed the study. No differences were noted between demographic data. The isoflurane consumption in the BIS group was 30-35% lower than in the control group (P<0.001). The time to awakening and duration of extubation in the BIS group were significantly less than the control group (P<0.001). Furthermore, analgesic consumption in the recovery room and sedation score during postoperative phase were similar between the groups. Significant differences were noted in recovery time between two groups (P<0.001).Conclusion: The addition of Bispectral index monitoring to standard monitoring reduced isoflurane usage. We found use of BIS hastened recovery time after isoflurane anesthesia.

Background: Today Anesthesiologists occasionally face with bradycardia during gastric surgery and recognized this phenomenon as a vagal reflex. The objective of this study is finding of anesthesia risk factors for bradycardia and prevention of its hazardous complications during gastric surgeries. Methods: In this retrospective study, fifty patients undergoing laparatomy and gastric surgery in Sina hospital between September 2009 to September 2013. They had been anesthetized with propofol or thiopental and their maintenance was kept by isoflurane or propofol were enrolled. The age, gender, underlying diseases, drug history, chemotherapy, kind of surgery, heart rate variability, onset time of bradycardia and its complication during a period of four years was noted.Results: Of Fifty patients, 31 males and 19 females was enrolled in this study. The mean age of patients was 48±8.3 yr; all patients had laparatomy under general anesthesia. The kind of surgery were mainly gasterectomy and gastrojejunostomy. The mean onset of episode bradycardia was 24.5±3.5 min after initiation of surgery incision, and most of the bradycardia was mild to moderate (47 patients) that with injection of atropine it resolved. There was no relationships between anesthetic drugs and anesthetic maintenance, age, gender, and incidence of bradycardia event during the surgery. The risk factors of bradycardia were, diabetes mellitus in seven patients, use of beta blockers in 17 patients in perioperative period and gastric cancer and chemotherapy (neoadjuant therapy) in three patients that lead to asystole, they were not response to standard treatment during surgery and lead to death.Conclusion: The history of gastric cancer and previous chemotherapy might be the only common factors that cause to bradycardia and irresponsible asystole during gastric surgery in these patients. It seems that only close monitoring and vigilant anesthesiologist require for treatment and prevention from adverse effect of such a sever bradycardia event.

Background: Intense Pulsed Light (IPL) technology is one of our new measures in treating dermatologic disorders including undesirable skin pigmentation. In contrast with lentigines and freckling of the skin, few reports about nevus spilus treatment using intense pulsed light have been published. The aim of current study was to evaluate efficacy and safety of nevus spilus treatment with an intense pulsed light device (Palomar Max-G IPL).Methods: Patients with diagnosed nevus spilus confirmed via histopathology, were treated by an intense pulsed light source using parameters according to the skin type and location of lesions in one to three consecutive treatment sessions at 14-21 day intervals for three month. Palomar Max-G Ò IPL hand piece is optimized for pigmented skin lesions and we used no additional filter. After each session, Photographs were taken from lesions with 10 mega pixel camera. Two months after finishing the treatment, the effect was evaluated base on close-up photographs.Results: Fourteen female patients were included. Significant improvement (76-100%) in one patient, good improvement (51-75%) in eight patients and fair to poor improvement (0-25%) in five patients were achieved. The commonest side effect of treatment was transient erythema resolved after six to eight hours. No permanent complication was reported. Younger patients and patients with shorter duration of lesion had better response to treatment; however the differences were not statistically significant. Only one recurrence has been seen. No significant relationship between age, gender, anatomical site of lesions and skin type with response rate was found.Conclusion: Intense pulsed light is seemed an effective and safe treatment for nevus spilus Treatment; however randomized control trials with longer follow-up periods are required to evaluate the efficacy and safety.

Background: Spontaneous hepatic rupture is a rare condition during pregnancy. Pregnant women with Hemolysis, Elevated Liver enzymes and Low Platelete count (HELLP) syndrome are more susceptible to hepatic rupture. It can occur per 40000 to 250000 pregnancies with high mortality and morbidity. There is no agreement on the best approach to this severe pregnancy complication. This is the case report of a spontaneous hepatic rupture associated with HELLP syndrome during pregnancy which occurred for the first time in the West Azerbaijan Province, Iran.Case Presentation: A 33 years old lady gravida 6, 3 intrauterine fetal deaths, 2 neonatal deaths at 30th weeks of gestation was admitted for preeclampsia. On admission, she had thrombocytopenia and elevated liver enzyme. Cesarean section was performed due to fetal distress and a preterm fetus was born. Inspection of the abdomen revealed a large hematoma in the right liver lobe associated with rupture of the capsule. Liver packing was performed by general surgeon and the abdomen was closed without repairing of fascia. In the 2nd day after operation, the patient was oriented but the abdomen reopened because of very low blood pressure. There was no severe liver hemorrhage so the liver was packed again with many surgicels. She developed acute kidney and liver failure, pleural effusion and a major coagulopathy post-operatively. Three weeks after surgery the abdomen was reopened for dehiscence and fascia was closed. The patient discharged after 40 days.Conclusion: Spontaneous liver rupture associated with HELLP syndrome is a rare and life-threatening complication of pregnancy. Unruptured liver hematoma is also a rare condition during pregnancy with a very difficult diagnosis. Using clinical diagnostic tests such as CT scan or MRI would be helpful to improve clinical outcomes.