مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال شصت و نهم شماره 11 (پیاپی 131، بهمن 1390)

Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide (NO), prostacyclin and mitochondrial ATP-dependent potassium channels in this regard. Male wistar rats (n=8) were anesthetized with sodium thiopental and their hearts were transferred to a Langendorff perfusion apparatus. All animals were randomly divided into nine groups as follow; in the ischemia-reperfusion group, hearts underwent 30 min of regional ischemia followed by 120 min of reperfusion. In oxytocin group, hearts were perfused with oxytocin 5 min after ischemia induction for 25 min. In other groups, 35 min prior to oxytocin perfusion, atosiban (a non-specific oxytocin receptor blocker), L-NAME (an NO synthase inhibitor), indomethacin (a non-specific cyclooxygenase blocker) and 5-HD (a specific mKATP channel blocker) were perfused for 10 min. In all groups, we measured CK-MB levels in the coronary effluent at the end of reperfusion. Moreover, coronary flow (mL/min) was measured at baseline, during ischemia period and 60 and 120 min after reperfusion. Oxytocin administration significantly reduced CK-MB level in oxytocin group as compared to ischemia-reperfusion group. Administration of atosiban, L-NAME, indomethacin and 5-HD prior to oxytocin perfusion abolished the effects of oxytocin on CK-MB levels. Administration of oxytocin during ischemia and reperfusion periods deceased CK-MB levels but infusion of atosiban, L-NAME, 5-HD and indomethacin inhibited oxytocin from exerting its effects.

Isosorbide dinitrate has been broadly used in the treatment of various ischemic heart diseases. Isosorbide is a nitric oxide donor which increases blood flow to tumors through vasodilatation and consequently accelerates the access of chemo-drugs to them. Furthermore, this drug has inhibitory effects on angiogenesis, tumor growth and metastasis in vivo. Moreover, its ant-inflammatory effects have also been reported. In the present study we evaluated the effects of isosorbide on the proliferative activity of fibrosarcoma WEHI-164 cell line and peripheral blood mononuclear cells (PBMCs). WEHI-164 fibrosarcoma cells and human PBMCs were cultured in complete Roswell Park Memorial Institute (RPMI) 1640 medium with 10% fetal bovine serum and 2×104 cells/mL for WEHI-164 and 2×105 cells/mL for PBMCs. The cells were then incubated at the exponential growth phase with different concentrations of isosorbide (4×10-6-1.6×10-3 M) for 24, 48 and 72 hours. Subsequently, isosorbide effects on proliferation of the cells were evaluated by trypan blue dye exclusion (TB) test and MTT assay. Statistical comparisons between groups were made by analysis of variance. The proliferative activity of WEHI-164 fibrosarcoma cells and human PBMCs treated with different concentrations of isosorbide, did not show any significant difference with untreated control cells. The results of this study showed that isosorbide neither had any significant effects on the proliferative activity of fibrosarcoma WEHI-164 cells nor on human PBMCs. Our findings suggest that anti-tumoral effects of isosorbide reported by other investigators may be mediated through non-cytotoxic mechanisms.

Cancer is a multistep process that develops very rapidly after its onset. Previous studies have confirmed antitumor effects of curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; diferuloylmethane) that can potentially prevent colon cancer development with low side-effects. Different methods have been performed to increase the efficiency and effectiveness of curcumin among which dendrosome, a nanoparticle created by Sarbolouki et al. was used in this study. The present study was undertaken to evaluate the effects of dendrosomal curcumin on rat colon cancer. In this study which was performed in Cancer Research Center of Tehran University of Medical Sciences in 2010 year, forty rats were equally divided into control, curcumin and curcumin-dendrosome groups. Animals received azoxymethane (15 mg/kg s.c.), a carcinogen, once a week for two weeks. Curcumin (0.2%) and curcumin-dendrosome were administered to the respective animals 2 weeks before the first and 14 weeks after the last azoxymethane injections. Eventually, colorectal specimens from tumoral and adjacent non-tumoral mucosal tissues were fixed in 10% formaldehyde, and passaged and embedded in paraffin. Histopathological and immunohistochemical studies were performed on the specimens. The mean number of lesions, nuclear/cytoplasmic ratio, epithelial stratification, loss of nuclear polarity, goblet depletion, structural abnormality and beta-catenin expression were higher in the control group compared to curcumin and curcumin-dendrosome groups. These parameters had significantly decreased in the dendrosomal curcumin group (P<0.05). The present study shows that dendrosome can be used as a suitable nanoparticle to increase curcumin efficiency in the prevention or treatment of colon cancer.

Nowadays, dendritic cells (DCs) have a special place in cancer treatment strategies and they have been used for tumor immunotherapy as they can induce immune response against tumor cells. Researchers have been trying to generate efficient dendritic cells in vitro; therefore, this research was done to generate them for use in research and tumor immunotherapy. This study took place at Urmia University in 2010-2011 years. In this study plastic adherent monocytes were incubated with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for five days. Finally, fully matured and stable DCs were generated by 48 hours of incubation in a monocyte conditioned medium (MCM) containing tumor necrosis factor-α (TNF-α) and epithelial cells. Phenotypic and functional analysis were carried out by using anti-CD14, anti-CD80, anti-CD86, and anti-CD83 monoclonal antibodies, and by determining their phagocytic activity, mixed lymphocyte reaction (MLR) and cytokine production, respectively. Dendritic cells were produced with high levels of surface molecule, i.e. of CD80, CD83, CD86, HLA-DR, expression and low levels of CD14 expression. Dendritic cells showed efficient phagocytosis and ability to stimulate T-lymphocytes. Moreover, dendritic cells could secrete high levels of interleukin-12 (IL-12) cytokine which was depictive of their full maturation. Measurement of the produced cytokines showed the generation of type-1 dendritic cells (DC1). Our study showed that skin epithelial cells could induce maturation of monocyte-derived dendritic cells (DCs). This feeder layer led to the production of efficient dendritic cells with the ability to be used for tumor immunotherapy.

The characteristic of stem cells in self renewal and differentiation to different types of cells has stimulated the interests for using stem cells as a starting material for generating insulin secreting cells. Weve evaluated the differentiation potential of Programmable cells of monocytic origin (PCMOs) into insulin producing cells effected from the growth factors and fibroblasts conditioned media (FCM). Peripheral blood monocytes of rat were cultured for 6 days in RPMI with 15% FBS, β- mercaptoethanol, MCSF and interleukin-3. Then, these cells were incubated in differentiation media with HGF, EGF, Nicotinamide, 15% fibroblasts conditioned media and glucose for 15days. Morphological differences of cells were studied by invert microscope. In several stages, the amounts of insulin in supernatant of cells were measured by radioimmunoassay kit. Also productions of insulin from differentiated cells were studied with DTZ special staining. In response to MCSF and IL-3, monocytes dedifferentiated. These programmable cells of monocytic origin (PCMOs) were capable of differentiating into insulin producing cells in differentiation media. The morphology of differentiated cells was similar to Beta cells and the amount of insulin in supernatant of differentiated cells was much higher than PCMOs (P<0.05). HGF, EGF, Nicotinamide and fibroblasts conditioned media are differentiation factors of PCMOs into insulin producing cells. According to the results insulin producing cells can be differentiated from programmable cells of monocytic origin in presence of fibroblasts conditioned media.

Ascorbic acid (AA) is not synthesized in the brain but it is actively transported through blood-brain barrier by SVCT2 cotransporter and it is stored in high concentrations with heterogeneous distribution in areas such as nucleus accumbens shell (AcbSh) in the mammalian brain. Previous studies have shown that Ascorbic acid injection into AcbSh decreases feeding; therefore, in the present study we evaluated the effects of oral Ascorbic acid pretreatment on changes in feeding upon its injection in AcbSh in adult male rats. Sixty-three adult male rats (220-280 g) were divided into five treatment and five pretreatment groups. The treatment groups included the control (intact) group, sham-operated Ascorbic acid group that received normal saline as vehicle, and three other groups that received different doses of ascorbic acid (10, 50 and 250 µg/rat) by injection into AcbSh for four days. The pretreatment groups received Ascorbic acid (100 mg/kg) for 15 days via gastric gavage before receiving the aforementioned doses in treatment groups into intra nucleus AcbSh. Feeding measurement was repeated every 12 hours by automatic metabolic cage. The results indicated that all injected doses of Ascorbic acid (10, 50 and 250 µg/rat) into nucleus accumbens shell decrease food intake (P<0.05) in rats and oral Ascorbic acid pretreatment had no effects in this regard. Our findings show that ascorbic acid is an effective factor in feeding regulation. Oral pretreatment seems to have no influence on the central effects of ascorbic acid in the nucleus accumbens shell.

Recent studies have demonstrated an essential role for IL-17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Furthermore, it has been shown that FoxP3+Treg cells play an important role in the suppression of autoinflammatory reactions. Although, previous studies have determined the immunomodulatory potentials of all-trans-retinoic acid (ATRA), but these immunomodulations have been mostly justified by alteration in Th1/Th2 cytokines. The present study was carried out to investigate the therapeutic effects of ATRA on EAE and its effects on T-helper cells responses. EAE was induced by MOG35-55 peptide and complete Freund's adjuvant in female C57BL/6 mice. The mice were allocated to two therapeutic groups (n=7 per group). Treatment with ATRA (500 μg/mouse; every other day) was initiated in treatment group on day 12 when they developed a disability score. EAE controls received vehicle alone with the same schedule. Signs of disease were recorded daily until day 33 when the mice were sacrificed. Splenocytes were tested for proliferation by MTT test, cytokine production by ELISA and FoxP3+Treg cell frequency by flowcytometry. ATRA significantly reduced the clinical signs of established EAE. Aside from decreasing lymphocytic proliferation (P<0.05), ATRA significantly inhibited the production of pro-inflammatory IL-17 (P<0.005) as well as IFN-γ (P<0.0005) upon antigen-specific restimulation of splenocytes. FoxP3+Treg cell frequency and IL-10 levels were not altered significantly. However, IFN-γ to IL-10 and IL-17 to IL-10 ratios decreased significantly (P<0.0005). Parallel to reducing autoreactive lymphocyte proliferation and cytokine production in favor of pro-inflammatory cytokines, all-trans-retinoic acid ameliorated established experimental autoimmune encephalomyelitis.

Persistence of left ventricular hypertrophy (LVH) in renal transplant recipients is associated with unfavorable outcomes. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after kidney transplantation. In this study we compared sirolimus (SRL) with calcineurin-inhibitor as primary immunosuppressants for the attenuation of left ventricular hypertrophy in renal transplantation recipients. In this prospective cohort study done in Shariati Hospital in 2010, we evaluated the effects of sirolimus and CNI on LVH of 55 renal transplant recipients. The cases (19) received sirolimus while the controls (36) received CNI while being matched for age and duration of transplantation. Data regarding blood pressure (BP), hemoglobin, serum creatinine, uric acid and lipid concentrations were assessed and changes in left ventricular (LV) mass were evaluated by echocardiography over a one-year follow-up. Left ventricular mass significantly decreased (P=0.0001) in the SRL group but blood pressure did not differ between the two groups. LV mass and LV mass index both decreased significantly (P≤0.05) but the difference was not associated with changes in BP. The difference in interventricular septal thickness at end diastole (IVSD) and posterior wall diameter (PWD) were significant (P≤0.05) in the SRL group but the difference in end diastolic diameter (EDD) was not significant. Conversion from CNI to SRL-based immunosuppressive therapy in RTRs is safe and SRL may decrease LVH. SRL seems to be safe and improve renal function without cardiac compromise in kidney transplant recipients.

Dabigatran etexilate is one of the few direct thrombin inhibitors with anti-coagulant activities and the following distinctive features: taken orally, no need to closely monitor for complications, and no need for regular dose adjustments. Relying on the above mentioned valuable advantages, dabigatran etexilate can be considered as a premier choice for the prevention of venous thromboembolism after knee replacement arthroplasty. Forty five patients undergoing 50 knee replacement surgeries were included in this case-series study undertaken in Hazrat Rasool Akram and Khatam-alanbia Hospitals during 2010. Dabigatran etexilate was administered for the prevention of venous thromboembolism after knee arthroplasty in doses of 110 mg in the first 1-4 h after surgery followed by daily doses of 220 mg for 10 days. Patients were examined 3 times and a color Doppler sonography was performed on the 11th day to check for venous thrombosis. Finally, the patients were re-examined at the end of the 1st and the 3rd months postoperatively. Only one out of 45 patients was diagnosed to have venous thrombosis on sonography done on the 11th day but the patient did not have any symptoms and repeat sonographies at the end of the 1st and the 3rd months postoperatively showed no venous thrombosis either. No complications were witnessed in the patients in the 3-month follow-up period. Dabigatran etexilate (220 mg/d for 10 days) can be an effective drug against venous thrombosis after total knee replacement surgeries.

Emergence agitation (EA) is a post-anesthetic problem which interferes with a child's recovery and presents a challenge in terms of assessment and management. In this study, we compared the effects of midazolam and ketamine as premedication in the management of EA in children aged 1-6 years. In this prospective, randomized clinical trial study, 58 children aged 1-6 years who were undergoing general anesthesia for elective surgery in Alzahra Hospital in Isfahan during 2008 until 2009. The patients were randomly assigned to receive 0.1 mg/kg midozolam (28) or 0.5 mg/kg ketamine (29) by IV route in the premedication room. All patients received a standardized anesthetic regimen and isoflurane was used for the maintenance of anesthesia. The incidence and severity of agitation (agitation score), severity of pain (pain score), anesthesia, recovery and extubation durations were recorded postoperatively. The prevalence of agitation in midazolam (21.4%) was lower than ketamine group (34.5%; P<0.05). In addition, the duration of agitation in ketamine group (21±16.67 min) was significantly higher than midazolam group (6.83±6.55 min), (P<0.05). However, no significant differences were seen in agitation score, pain score, anesthesia, recovery or extubation durations in the two groups (P>0.05). The study showed that midazolam could reduce the frequency of agitation better than ketamine but both drugs were able to reduce the severity of agitation after short-time surgeries in young children.