Tehran University Medical Journal

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Macrophage colony stimulating factor (M-CSF) has previously been shown to affect the differentiation of cells of the mono-nuclear phagocytic line. More recent studies indicate that M-CSF may have a role in pregnancy. In the present study, the expression of M-CSF in the human placenta was demonstrated. Placental mRNA was isolated and used as template for synthesis of complementary DNA (cDNA). The presence of M-CSF related sequences in the cDNA was shown by PCR and RT-PCR reactions in which M-CSF specific primers were used. In addition, it was shown that a 2.4 kb cDNA after electrophoresis and transfer to a nylon filter, hybridized with a digoxygenin labeled M-CSF specific probe.

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Background: Cardiac connective tissue dysplasia syndrome consists of mitral valve prolapse (MVP), anomalously located chordae tendinae of the left ventricle, or a combination of the two. MVP is marked by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. The nonclassic form of MVP carries a low risk of complications. Patients with severe classic MVP can suffer from mitral regurgitation (MR), infective endocarditis, and, infrequently, sudden death from cardiac arrest. Anomalously located left ventricular chordae tendinae are fibrous or fibromuscular bands that stretch across the left ventricle from the septum to the free wall. They have been associated with murmurs and arrhythmias. The purpose of this study is to assess the performance, as measured by the physical working capacity (PWC170) and maximal oxygen consumption (VO2 max), in athletes with cardiac connective tissue dysplasia syndrome.
Methods: Of the 183 male athletes studied, 158 had cardiac connective tissue dysplasia syndrome and 25 were normal, healthy controls. Their mean age was 16.23 (± 5.48) years and mean training time was 5.2 (±- 4.6) years. Athletes with cardiac connective tissue dysplasia syndrome were divided to four groups. Group 1 consisted of those with MVP Group 2 had patients with an additional cord in left ventricle Group 3 was made up of athletes with a combination of MVP and additional cord Group 4 contained athletes with a combination of MVP and MR. All sportsmen were studied by echocardiograph, veloergometer, and those with arrhythmias were studied and recorded using a Holter monitor.
Results: The most common form of this syndrome in our study groups was MVP. The PWC170and VO2 max among the athletes with the combination of MVP+MR (Group 4) was lower than that of athletes in other groups (P<0.05). The most common arrhythmia among the athletes with anomalously located left ventricular chordae, Group 2, was Wolf-Parkinson-White (WPW) syndrome and early repolarization syndrome. The PWC170 and VO2 max in athletes with WPW syndrome, was lower than the other athletes who did not have WPW syndrome (P<0.05).
Conclusion: The lowest PWC170 and VO2 max were in those athletes with a progressive abnormality. However, the PWC170 and VO2 max among athletes with anomalously located left ventricular chordae was normal. Therefore, among athletes with a combination of anomalously located left ventricular chordae and disruption of rhythm, the PWC170 and VO2 max are lower than normal.

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Background: Parkinson's disease (PD) is a degenerative neurodopaminergic disease in nigrostriatum pathway of animals and human, the resultant loss of nerve terminals accompanied by dopamine-glutamate and other related neurotransmitters-imbalances in this pathway are responsible for most of the movement abnormalities. Increasing evidence suggests that an inflammatory reaction accompanies the pathological processes caused by Cyclooxygenase-2 (COX-2) seen in many neurodegenerative disorders, including PD. These findings have not indicated any evidence based on the effect of selective and non selective COX-2 inhibitors on the rigidity of PD.
Methods: The rats left substantia nigra pars compacta (SNc) was destroyed using the electrical lesion thus PD model was created. Then oral aspirin and celecoxib (200, 400 mg/kg) were administrated to parkinsonian rats acutely and then the rigidity was evaluated using Murprogo's Method.
Results: Both compounds were able to decrease the rigidity of parkinsonian rats (p<0.05) respectively but selective cox-2 inhibitor (celecoxib) was found more effective and potent than that of non selective cox-2 inhibitor (aspirin). Conclusion: The findings suggest that COX-2 inhibition decreases the rigidity of PD in the animal model. Therefore, as results of the study COX-2 inhibition was shown good evidence based on the use of aspirin and celecoxib and PD affiliated rigidity improvement that this can be beneficial and interest for neuroscientists. These findings are additional pharmacological and medicinal information to further assess of non steroidal anti inflammatory drugs (NSAIDs) as alternative therapeutic agents for PD affiliated rigidity treatment. Further experiments seem to be necessary to complete this research such as investigation the effects of NSAIDs on the striatum neurotransmission pathway

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Cyclooxygenase 2 is a key enzyme which converts arachidonic acid into prostaglandins. Cyclooxygenase 2 is triggered by inflammatory stimuli, such as cytokines. Its expression increases in tumors and Alzheimer's disease and ovarian hyperstimulation syndrome. Polycystic ovarian syndrome is a heterogeneous disease characterized by pathological angiogenesis and chronic anovulation. In the present study, the probable role of cyclooxygenase 2 in Wistar rats with polycystic ovarian syndrome was investigated.
Methods:  Thirty female Wistar rats (170-200 gr) were equally divided into three groups: 2 mg estradiol valerate was intramuscularly administered to each rat in the experiment group or group 1 the rats in group 2 were regarded as the sham group and received sesame oil injections and group 3 or the control group received no injections. After 60 days of treatment, animals were anaesthetized with chloroform and killed by decapitation. Ovaries were collected for histological and immunohistochemical evaluations. All the experiments were repeated three times.
Results:  Morphologically, ovaries from the control group exhibited follicles in various stages of development and many fresh corpus luteum. In estradiol valerate group small follicles in early development were observed in addition to follicles showing evidence of atresia and many large cysts with thickened theca cell layer. Corpus luteum was rare or absent in group 2. The immunohistochemical analysis for cyclooxygenase 2 expression showed an increased expression of cyclooxygenase 2 enzyme in group 1.
Conclusion: The results suggested the involvement of cyclooxygenase 2 in the progression to polycystic ovarian syndrome in a rat model.

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Background: Transitional Cell Carcinoma (TCC) is the most common type of urinary bladder cancer. Cyclooxygenase-2 (COX-2), a key enzyme in prostaglandins biosynthesis, has been introduced as a new candidate for targeted therapy in this cancer. In this study, we investigated the expression of COX-2 in urinary bladder TCCs and its relationship with clinicopathological parameters such as tumor grade and stage.

Methods: This cross-sectional study was performed in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011. Pathology reports of patients with definite diagnosis of urinary bladder TCCs who had undergone Transurethral Resection (TUR) were reviewed and 40 cases were selected. Subsequently, COX-2 expression was assessed immunohistochemically by the examination of paraffin embedded tissue blocks. Staining in more than 5% of tumor cells was considered as positive expression.

Results: COX-2 was expressed in 52.5% of the patients. High-grade tumors revealed a higher (87.5%) COX-2 expression versus other grades of the lesions and there was a statistically significant difference in COX-2 expression between them (P<0.001). Patients' age was also related to the expression of this marker (P=0.03). In contrast, this marker did not correlate with other characteristics including gender, lymphatic invasion or tumor stage. In addition, perineurial or vascular invasions were not detected in any of the patients.

Conclusion: COX-2 expression was seen in more than half of our patients and it had a marked relation to tumor differentiation. Accordingly, this molecule may be a useful tumor marker in the assessment of urinary bladder cancers.

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Background: Pulseoximetry is widely used in the critical care setting, currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SPO2 (puls-eoximetry oxygen saturation) in intensive care unit after cardiac surgery. Our objective was to compare pulseoximetry with arterial oxygen saturation (SaO2) during clinical routine in such patients, and to examine the effect of mild acidosis on this relationship.
Methods: In an observational prospective study 80 patients were evaluated in intensive care unit after cardiac surgery. SPO2 was recorded and compared with SaO2 obtained by blood gas analysis. One or serial arterial blood gas analyses (ABGs) were performed via a radial artery line while a reliable pulseoximeter signal was present. One hundred thirty seven samples were collected and for each blood gas analyses, SaO2 and SPO2 we recorded.
Results: O2 saturation as a marker of peripheral perfusion was measured by Pulseoxim-etry (SPO2). The mean difference between arterial oxygen saturation and pulseoximetry oxygen saturation was 0.12%±1.6%. A total of 137 paired readings demonstrated good correlation (r=0.754 P<0.0001) between changes in SPO2 and those in SaO2 in samples with normal hemoglobin. Also in forty seven samples with mild acidosis, paired readings demonstrated good correlation (r=0.799 P<0.0001) and the mean difference between SaO2 and SPO2 was 0.05%±1.5%.
Conclusion: Data showed that in patients with stable hemodynamic and good signal quality, changes in pulseoximetry oxygen saturation reliably predict equivalent changes in arterial oxygen saturation. Mild acidosis doesn’t alter the relation between SPO2 and SaO2 to any clinically important extent. In conclusion, the pulse oximeter is useful to monitor oxygen saturation in patients with stable hemodynamic.

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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.

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Background: Nausea and vomiting is one of the most important complications in chemotherapy. Serotonin and dopamine are important neurotransmitters in nausea and vomiting. It seems that oxygen therapy and increase oxygen saturation can cause decrease these neurotransmitters. The aim of this study was to investigate the relationship between arterial oxygen saturation (SaO2) of patients and chemotherapy-induced nausea and vomiting. Methods: A descriptive-analytical study was performed in Koosar Hospital in Semnan, Iran, from 19 September 2013 to 25 April. At first, SaO2 of 30 patients in three periods (pre, during and post chemotherapy) were measured. Severity of nausea and vomiting in three days after chemotherapy was measured with an index of nausea, vomiting and retching (Rhodes Index). Also during chemotherapy, anxiety and depression of patients was measured with Hospital Anxiety and Depression Scale (HADS). Results: In this study thirty patients were evaluated. Most of them were women (66%) with mean age of 55.07±11.9 years old. The most common cancer in patients was breast cancer (46.7%). Mean of SaO2 was 92.1%±3.4 that was not significant difference during the chemotherapy. Mean of nausea and vomiting severity in first day of chemotherapy was (3.27±5.5), in second day was (4.5±6.2) and in third day was (7.2±8.7). The Pearson correlation coefficient did not show the relationship between oxygen saturation with severity of nausea and vomiting (P>0.05). Although severity of anxiety of patients was significant relationship with nausea and vomiting in third day (P=0.03). Conclusion: In this study there was no significant relationship between oxygen saturation and severity of nausea and vomiting, but anxiety of patients was related to nausea and vomiting in third day. Chemotherapy-induced nausea and vomiting was more common in third day and it seems that further research is needed for relationship between oxygen saturation and nausea and vomiting in third day of treatment.

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Background: Platelet storage is complicated by deleterious changes that cause progressive structural and functional damages, so-called platelet storage lesion (PSL). PSL is commonly manifested by augmented platelet activation which is also associated with the increased levels of reactive oxygen species (ROS). Whether ROS generation increases during the storage of platelet concentrates and whether it will be correlated with P-selectin expression as a valid marker of platelet activation was investigated in this study. Methods: In our experimental study, six PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO). All the platelet products met the standard quality assessment based on AABB guidelines. Washed platelets were subjected to flow cytometry analysis for the evaluation of P-selectin expression and intracellular ROS production using DHR 123 in day 0, 1, 3 and 5 after storage. Statistical data were analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test. For correlations, linear regression analysis was applied. P values of less than 0.05 were considered to be significant. Results: Platelets ROS generation significantly increased from day 0 to day 5 of storage (P= 0.0002). This observed gradual increase was also directly correlated with the increasing levels of P-selectin expression during platelet storage (r= 0.72, P= 0.0001). Conclusion: Our study showed significant increases in ROS generation during the storage of platelet concentrates correlated with the increments of P-selectin expression as an important marker of platelet activation. This finding suggests that the analysis of ROS generation can also be considered a marker of platelet activation during storage. However, whether ROS generation first induces platelet activation or platelet activation during storage triggers ROS generation is still remain to be determined.

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Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS) that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause free radicals which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances known as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated by hope that better exploration of the factors involved in the occurrence and spread of cancer will improve the identification of treatment aims.