Tehran University Medical Journal

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Background: Human plasminogen is a plasma glycoprotein synthesized mainly in the liver. Conversion of plasminogen to plasmin by plasminogen activators is a key event in the fibrinolytic system. In this study, we investigated the effects of two anti-human plasminogen monoclonal antibodies, A1D12 and MC2B8 on Glu-plasminogen activation in presence of u-PA, t-PA and streptokinase.

Methods: Producing of Hybridoma antibodies was performed by fusion of spleen cells from BALB/C mice immunized with Glu-plasminogen and NS1 myeloma cells. Antibody binding to Human Glu-plasminogen was assessed using an ELISA assay. Activation of plasminogen was determined by measuring plasmin generation using the chromogenic substrate S-2251 and the effect of monoclonal antibodies, A1D12 and MC2B8 on plasminogen activation in solution was then evaluated. Initial rates and kinetic parameters of plasminogen activation in the presence of monoclonal antibodies were calculated. The effect of the monoclonal antibody MC2B8 on the rate of plasmin hydrolysis was measured. The effect of F(ab&apos)2 fragment of A1D12 on u-PA catalyzed-plasminogen activation also compared with the effect of the whole antibody in this reaction.

Results: ELISA assay showed that the antibodies reacted well with antigens. A1D12 increased the maximum velocity (Vmax) of plasminogen activation by each of the three plasminogen activators and MC2B8 decreased it. In all activation reactions, the KM value of plasminogen activation did not significantly change in the presence of antibody A1D12 whereas antibody MC2B8 increased the KM value of plasminogen activation by u-PA, fibrin monomer dependent t-PA and streptokinase. Monoclonal antibody MC2B8 had no significant effect on plasmin hydrolysis rate of synthetic substrate S-2251. Activation rate of plasminogen by u-PA in the lower concentration of F (ab)2 fragment of A1D12 was identical to activation in the presence of the whole antibody.

Conclusion: The binding of the A1D12 F(ab) region to Glu-plasminogen increases the catalytic efficiency of plasminogen activation by plasminogen activators. Therefore, it may be useful to apply clinically A1D12 for the therapy of thromboembolic events such as myocardial infarction by humanizing the F(ab) fragment of the A1D12 antibody. Inhibition pattern of antibody MC2B8 obey the mixed type of enzyme inhibition by binding the antibody probably at, or near, the cleavage site of Glu-plasminogen.

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Background: This study was designed to investigate the process of bone formation caused by implantation of octa calcium phosphate (OCP) in rat tibiae.

Methods: We used 25 young male Sprague-Dawley rats. A full thickness standardized trephine defect, 3-mm in diameter, was surgically created on the superior end of right and left tibia. Amount of 6-mg synthetic Octa calcium Phosphate was implanted into a bony defect on the right tibia as a experimental group. No OCP particles were implanted in the left tibia as a control group that was otherwise treated identically. Bone formation was examined histologically on 7th, 10th, 14th, 21st, 28th days after implantation.

Results: In the experimental group, on the 7th day after implantation, a few clusters of cartilage cells were observed between the OCP particles near the defects margin. Osteogenesis was initiated locally between the OCP particles in central position of the defects on 10th day after implantation. By 14th day after implantation, Alcian blue staining showed hypertrophic chondrocytes that replaced by new bone. In addition to bone formation locally around the OCP particles, more apposition of new bone was observed near the defects margin on 14th and 21st days after implantation. At the end of study implanted OCP was surrounded by newly formed bone. In the control group, at the end of study, bone formation was observed only along and near the defects margin.

Conclusion: These results demonstrate that octa calcium phosphate could be used in the repair of the long bone defects.

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Background: The male antifertility activity of Gossypol, the active ingredient of cotton seed, inspired the idea for development of an agent with male contraceptive activity. The result of subsequent studies lead to the discovery of several class of compounds with antifertility activity. In this study the antifertility activity of iso-Propyl and iso-Butyl derivatives of dihydropridine were evaluated.
Methods: The two aforementioned compounds were administered subcutaneously in (10 mg/kg/day) dose to male rats. The animals were treated and kept according to the TUMS committee recommendations on ethical and animal maintenance considerations. Sixty days after the first injection the following fertility and histological indices were evaluated, animal’s body weight difference (B.W.D), sperms motility, sperm viability, ESR (epididymal sperm reserve), DSP (daily sperm production), serum testosterone concentration, fertility index, GSI (gonado somatic index). Histological indices are respectively the area and circumference of seminiferous tubules, each testis and their crosswise dissections, the diameter of seminiferous tubules and the number of seminiferous tubules per square millimeter, that were determined.
Results: The values of the two test groups were determined and compared with the results of normal group that were using normal saline only and the blank that were receiving propyllenglycol only.
Conclusion: The significant inhibitive activity of candidate compounds on animal's physiologic indices were in accordance of our pervious estimation of compounds activity as (lead compound) for synthesis and preparation of new compounds with male contraceptive activity

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Background: MSCs have been isolated from a variety of mammals by the plastic adherence method. However, this method can be problematic due to the unwanted growth of hematopoietic cells and non-MSCs. The potential of MSCs to differentiate along multiple lineages is the key to the identification of stem cell populations in the absence of molecular markers. In the present study, we describe a homogeneous population of MSCs from mouse bone marrow isolated using an improved plastic adherence method that employs frequent medium change (FMC) at the initial hours of harvested bone marrow cell culture.
Methods: Balb/c mice were sacrificed and whole bone marrow cells were aspirated from the femur and tibia and then cultivated in six-well plates. After 3-4 hours of culture, old medium was removed and fresh medium was added. FMC was performed every eight hours over a 72 hour period. When primary cultures became nearly confluent, the first passage was performed. These cells were then used for further examination. To investigate their mesenchymal nature, the cells were allowed to differentiate into mesenchymal lineages and examined at each passage up to the tenth passage for surface antigens by flow cytometry.
Results: We achieved purified populations of fibroblast-like cells in the two weeks after culture initiation. The cells were capable of differentiating into osteocytes and adipocytes. Isolated MSCs were reactive to the CD44, Sca-1, and CD90 cell surface markers. MSCs were negative for hematopoietic surface markers such as CD34, CD11b, CD45, CD31, CD106, CD117 and CD135.
Conclusions: This protocol provides an efficient isolation of homogeneous populations of MSCs from mouse bone marrow.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Paraquat is an herbicide produced and used prevalently worldwide. Studies have shown that lung fibrosis induced by paraquat can be prevented or delayed by certain antioxidants, iron chelating agents, melatonin, and, recently, blood pressure lowering drugs such as captopril.
Methods: The protective effects of captopril on paraquat toxicity were studied using RT-PCR and immunohistochemistry to determine the gene and protein expression of p53 and Bcl-2 in lung tissue samples from rats treated with captopril before and after exposure to paraquat.
Results: We found no significant difference in the gene and protein expression of p53 in different tissue samples, except for mRNA levels in the lung tissue of captopril-treated rats. However, the protein expression of Bcl-2 is greater in tissue from rats exposed to paraquat alone and paraquat together with pre- and posttreatment with captopril compared to tissue from untreated control rats and from those treated with captopril alone, which can be due to inflammatory responses of lung tissue. By RT-PCR, we were unable to detect Bcl-2 in lung tissue samples.
Conclusion: These results show that paraquat does not induce significant DNA damage therefore, the gene and protein expression of p53 was not changed. Paraquat does induce lung tissue inflammation, which in turn increases Bcl-2 protein expression. Finally, captopril had no significant effect on the lung tissue toxicity induced by paraquat. Considering these results and the cellular interactions in lung tissue, we suggest that complementary assays and in-vitro cell culture experiments be performed to further elucidate the molecular events underlying paraquat lung toxicity.

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Background: Dimethyl sulfoxide (DMSO) has been used as a solvent for many drugs in ischemic experiments. DMSO has many biological benefits, including antioxidant, anti-inflammatory, platelet aggregation inhibiting and cell membrane stabilizing effects. Moreover, some experimental studies report that DMSO has a neurprotective effect in permanent focal cerebral ischemia. Despite the effect of DMSO on the cortex, striatum injuries and motor neurological dysfunctions in transient focal cerebral ischemia are not completely clear.

Methods: Thirty-six male Sprague-Dawley rats weighing 300-350 g were divided into saline- (control) and DMSO-treated groups. Under chloral hydrate anesthesia (400mg/kg, ip), transient focal cerebral ischemia was induced by 90-min middle cerebral artery occlusion (MCAO) followed by 23-h reperfusion. Rats received saline (n=11) or 2% DMSO intraperitoneally at doses of 0.01 (n=11), 0.1 (n=7) and 0.2 (n=7) ml/kg 30 min prior to induction of ischemia. Twenty-four hours after MCAO, the neurological deficit scores were ascertained. Cortical and striatal infarct volumes determined by triphenyltetra-zolium chloride staining. 

Results: Administration of DMSO at doses of 0.1 and 0.2 ml/kg significantly reduced cortical and striatal infarct volumes (p<0.001), while rats receiving the 0.1 ml/kg dose had infarct volumes similar to those of the control group (p=0.225). Moreover, only 0.2 ml/kg doses of DMSO significantly reduce neurological motor dysfunction (p<0.001).

Conclusions: Findings of this study indicate that DMSO is a potent neuroprotective agent against transient focal cerebral ischemia in rat. Moreover, our data also suggest that DMSO may be a candidate for acute stroke treatment.

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Background: Because of eventual side effects of chemical drugs, the efficacy of natural wound healing accelerators in long-term diseases and some situations is demanded to practitioners. The initial aim of our study was to assess full thickness excisional skin wound healing and inflammation diminution, Morphometrically and Histopathologically, after topical application of dried extract of Echinacea purpurea aerial part in rats, compared with zinc oxide.

Methods: Sixty wistar rats received four full thickness excisional wounds with the aim of surgical punch on the back skin under surgical anesthesia. All rats were randomly divided into groups 1, 2 and 3, of Echinacea purpurea, zinc oxide and control, respectively. All of them were treated topically once a day for 21 uninterrupted days. Healing of the wounds was daily measured by taking digital photographs and analysis. Histopathologic assessment was carried out in the 0th, 3rd, 7th, 14th, and 21st days of treatment period as well, and wound healing was assessed using 1 to 6 healing grades.

Results: According to Morphometric findings, the wound contraction rate in group 1 after 21 days of skin punching, with wound size of 0.18±0.03 mm² in contrast with group 2, 2.81±0.21mm², was much higher than that in other groups. Group 1 with wound contraction rate of 2.5 times in the day 7 and 3 times in the day 14 more than group 2, had the best wound contraction (p<0.01). histopathologic assessment revealed that, overall healing rate in the group 1 was highest (p<0.01).

Conclusion: Echinacea purpurea dried herbal extract could be a new capable remedy to accelerate skin wound healing because of its potential anti-phlogosis and wound healing stimulatory properties.

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Background: Previous studies suggested that stressful events that release Glucocorticoid from adrenal cortex and also injection of agonists of glucocorticoids receptors probably affect emotional learning and memory process and modulate them. The aim of this study was to determine the effects of acute stress and systemic injection of Corticosterone (as agonist of glucocorticoid receptors) on acquisition (ACQ), consolidation (CONS) and retrieval (RET) of emotional memory in rat.

Methods: In this experimental study we used 180 male Wistar rats (220-250). At the first rats was training in one trial inhibitory avoidance task. On the retention test given 48 h after training, the latency to re-enter the dark compartment of the apparatus (Step-through latency, STL) and the time spent in light chamber (TLC) were recorded during 10 min test. Intraperitoneal corticosterone in doses of 0.5, 1 and 3mg/kg injected 30min before, immediately after instruction and 30min before retrieval test. Also some groups received 10min stressful stimulation by restrainer at the same time. At the end locomotor's activity was measured for all animals.

Results: The data indicated that administration of corticosterone 30min before ACQ (1mg/kg), and immediately after CONS (1, 3mg/kg) enhance and 30min before RET (1, 3mg/kg) impair emotional memory (p<0.05). Acute stress impaired emotional memory in all phases (p<0.05). Also acute stress and injection of Corticosterone have not significantly affect motor activity. 

Conclusions: These findings show that Glucocorticoid receptors in activation dependently plays an important role in modulation of emotional spatial memory processes (ACQ, CONS and RET in new information) for emotional events and these effects varies in different phases.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Ample evidence indicated that glucocorticoids, when administered after training, enhance memory consolidation in a variety of tasks. The mechanisms underlying the enhancing effects of glucocorticoids on memory consolidation are not well known. The aim of this study was to determine the role of NMDA receptors and calcium channels in glucocorticoid-induced enhancement of avoidance memory consolidation in mice.
Methods: Experiments were performed on 166 male albino mice (about 30gr). The animals were trained in an inhibitory avoidance (IA) task (0.5mA shock for 3 seconds). In Experiment 1, dose- response effects of corticosterone on memory consolidation were determined. Immediately after training in IA task, the animals were received different doses of corticosterone (0.3, 1 or 3mg/kg). In Experiments 2 and 3, effects of corticosterone on memory consolidation were examined in the presence or absence of verapamil, a calcium channel blocker, (2.5, 5 or 20mg/kg) or MK-801, an antagonist of NMDA receptor (0.1mg/kg), respectively. In all experiments, retention test was done two days later.
Results: Results from first experiment revealed that corticosterone at dose of 0.3mg/kg significantly improved consolidation of avoidance. Data from experiments 2 and 3 showed that both verapamil, in doses of 2.5 and 5mg/kg, and MK801 significantly blocked corticosterone-induced enhancement of memory consolidation.
Conclusion: Finding of this study clearly demonstrated that the memory enhancing effects of corticosterone, at least in part mediate via calcium channels and NMDA receptors.

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Background: In according to immunomodulatory effect of probiotics and effect of these bacteria on the effectiveness of immune responses, at the present work we proposed the evaluation of oral administration of L.acidophilus on the immune statues in BALB/c mice bearing breast cancer.
Methods: A total of 30 In-bred BALB/c mices aged from six to eight weeks weighting 25-30g were randomly enrolled in our study, in two groups each consist of 15 mices. The L.acidophilus ATCC4356 strain used in this study was inoculated in MRS broth and cultivated for a day at 37°^C under anaerobic conditions, collected by centrifugation and resuspend in Phosphate Buffer Saline (PBS). After preparation of proper amount of these suspensions it was orally administered to the mice with a gastric feeding, Control mices received an equal volume of PBS in duration of study.
Results: Results showed the increase in production of IFnγ (p<0.005), and decrease in production of Th2 cytokines such as IL4 (p=0.347) in the L.acidophilus administered mice in comparison to control group of mice. In addition the proliferation of immune cells in probiotic group was significantly higher than controls, and most importantly probiotic administered mice showed an increase in survival rate of this group compared to control mice (p<0.001).
Conclusion: Results of our study suggested that daily consumption of Lactobacillus acidophilus can regulate immune responses skewed Th1 balance that is needed against tumor, further studies is needed to investigate the other mechanisms of this effect.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Ascorbic acid improves cognitive impairments in several experimental models. Diabetes causes learning and memory deficits. In this study we hypothesized that chronic treatment with ascorbic acid (100mg/kg, p.o) would affect on the passive avoidance learning (PAL) and memory in control and streptozocin-induced diabetic rats.
Methods: Diabetes was induced by a single i.p. injection of STZ (60mg/kg). The rats were considered diabetic if plasma glucose levels exceeded 250mg/dl on three days after STZ injection. Treatment was begun at the onset of hyperglycemia. PAL was assessed 30 days later. Retention test was done 24 h after training. At the end, animals were weighted and blood samples were drawn for plasma glucose measurement.
Results: Diabetes caused impairment in acquisition and retrieval processes of PAL and memory in rats. Ascorbic acid treatment improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. Ascorbic acid administration also improved the body weight loss and hyperglycemia of diabetics. Hypoglycemic and antioxidant properties of the vitamin may be involved in the memory improving effects of such treatment.
Conclusion: These results show that ascorbic acid administration to rats for 30 days from onset of diabetes alleviated the negative influence of diabetes on learning and memory. Comparing with other nootropic drugs, vitamins have fewer side effects. Therefore, this regimen may provide a new potential alternative for prevention of the impaired cognitive functions associated with diabetes after confirming by clinical trials.

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Background: Proteolytic enzymes, especially collagenases, are used for digestion of extracellular matrix, cell isolation and primary culture. Because of the problems in purification and low amount of collagenases in bacterial or animal sources, it is important to find new sources of the enzymes. So, in the present study actinidin, a plentiful protein in kiwifruit was purified and a mixture of actinidin and trypsin was applied to isolate rat aortic endothelial cells. Methods: Aortic endothelial cells were isolated using digestion solution containing different concentrations of actinidin (from 2 to 16 mg/ml) and trypsin (0.3, 0.6, 1.2 and 2.4 mg/ml) in different times (from 15 to 90 minute). Isolated cells were cultured in DMEM culture medium. Isolated cells were identified by morphological characteristics and immunocytochemical staining viability of separated cells was estimated by trypan blue exclusion test. Results: Actinidin in concentration of 10 mg/ml with trypsin in concentration of 1.2 mg/ml for one hour could isolate rat aortic endothelial cells. In this condition the viability of cells was estimated 90%. Morphological and immunocytochemical charac- teristics confirmed the isolated cells as endothelial cells. Conclusion: The results showed that the mentioned mixture of actinidin and trypsin has not considerable toxic effects on separated cells and is a novel and suitable option for isolation of rat aortic endothelial cells

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Background: Efforts have been made worldwide to identify and to study parasites of laboratory animals, aiming at the achievement of proper procedures for eradication of parasitic infestations, considering the important role of these animals in scientific research. There is no sufficient data about parasitic infestations of Laboratory animals which are kept in conventional systems in Iran. In this scope, peresent study was designed to investigate the presence of ectoparasites and endoparasites in conventionally maintained laboratory rats (Rattus norvegicus) and in mices (Mus musculus).
Methods: A descriptive cross-sectional study was performed on 240 randomly selected rats and mice from two different animal houses in Kerman city, Iran. Skin scraping blood samples and alimentary tract contents of all animals were fully examined for the presence of parasitic infections.
Results: In the first animal house, Nosopsylla fasciatus (flea), Hymenolepis dimminuta, Entamoeba muris and Cryptosporidium spp. infestation were diagnosed respectively in 35.41%, 36.1%, 3.57%, and 1.25% of rat colonies but only Entamoeba muris infestation was detected in 4.58% of mice colonies. In the second animal house, 2.5% and 2% of rat and mice colonies were infected by Entamoeba muris.
Conclusion: Based to presence of asymptomatic parasitic infection in conventionally maintained laboratory animals, regular periodical samplings, precise sanitary monitoring of barrier maintained system, environment and food seem necessary in animal houses. Eradication of parasites could eliminate the confounding effects of these infections on researches and additionally decrease the risk of zoonotic disease transmission to investigators and animal house personnel's.

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Background: Numerous evidences indicate that various environmental stresses during pregnancy affect physiological behavior of the offspring. This experimental study was designed to investigate the effect of noise stress during prenatal period of rats on spatial learning and memory and plasma corticostrone level in postnatal life.
Methods: Three groups of pregnant rats were given daily noise stress with durations of two and/ or four hours in last week of pregnancy period. The fourth group was left unstressed. The male offspring from the unstressed and different stressed groups were assigned as controls and stressed groups. The animals were introduced to a spatial task in Morris water maze 4 trials/day for five consecutive days. The probe test was performed on the 5^th day of the experiment. The delay in findings and the distance passed to locate the target platform were assessed as the spatial learning.
Results: Our results showed that prenatal exposure to noise stress for two and/ or four hours a day, leads to impaired acquisition of spatial learning in the postnatal animals. The plasma level of corticostrone in the two stressed groups of rats markedly matched with their behavioral function. Prenatal exposure to 1- hour noise stress revealed no effects on the offsprings' behavior and plasma corticostrone level.
Conclusion: Based on our study results, it seems that applied range of stress which is executed through the noise stress could increase the plasma corticostrone level and could decrease spatial learning and memory of adult male offspring.

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Background: Alprazolam belongs to benzodiazepine family and is increasingly used these days by pregnant women. It should be noticed that alprazolam exposure during pregnancy may have teratogenic effects on the fetus. Till now, limited studies have been conducted on the teratogenic effect of alprazolam. In this study, teratogenicity of alprazolam intake during pregnancy and its effects on fetus development was investigated.
Methods: About 20 virgin rats of known age and weight were selected. After being pregnant, they were divided into four groups which contained five animals in each group: Negative and positive control groups. The case group exposed to 1 to 6 mg/kg/day alprazolam. The fetuses were first studied macroscopically regarding anomalies, and then histologically and histochemically to inspect the defects of tissue organogenesis.
Results: Our results show that there was significant difference especially at the dose 6 mg/kg weight and length of the cases compared to the control group. It appeared that at the dose of 6 mg/kg/day, cleft lip and palates were seen in the animals. The highest anomalies of limbs were also seen at the dose of 6 mg/kg/day. The statistical results indicate that alprazolam intake during the second half of pregnancy can lead to irreversible anomalies.
Conclusion: Our results indicate that alprazolam in doses higher than 4 mg/kg/day might cause teratogenic effect. It seems that benzodiazepine therapy among pregnant woman would be better to avoid during the first trimester and multidrug regimens.

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Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Metformin which is effectively used for the treatment of anovulatory PCOS improves pregnancy rate and endometrial receptivity and reduces the risk of miscarriage. The aim of this study was to evaluate the effects of metformin on the endometrium, the number of fetuses and hormonal levels of PCOS rats. Methods: Forty female adult Sprague-Dawley rats were assigned randomly into four equal groups. Group I: control rats, group II: rats receiving metformin (150 mg/kg/day), group III: Estradiol Valerate-induced PCOS rats (4 mg/rat) and group IV: induced PCOS rats receiving metformin. Body weight and serum levels of glucose, LH, FSH, testosterone, progesterone and estradiol were measured. Following mating, each group was divided into two subgroups and the rats were sacrificed on the 5th and 15th day of gestation to evaluate endometrial reaction to implantation and fetus count, respectively. Results: Hormone assay showed a significant increase in testosterone, estradiol, LH, FSH and blood glucose levels in group III compared to the controls (P≤0.01) and a significant decrease in blood glucose in group IV versus group III (P≤0.01). Progesterone concentration had no significant differences between groups III and the controls. Weight was higher in group III than group I but it had no decrease after metformin administration. No significant differences were detected regarding implantation rate and number of fetuses in all rats. Conclusion: Metformin has significant effects on pregnancy rate and the hormonal and blood glucose levels of Estradiol Valerate-induced PCOS rats.

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Background: Numerous studies have shown the protective effects of saffron against oxidative damage in a global model of cerebral ischemia, but its effects on brain edema and oxidative ischemic injury in focal ischemic stroke are not completely understood. Therefore, this study was designed to investigate the effects of saffron on brain edema, infarct volume, antioxidant enzyme activity (glutathione peroxidase and superoxide dismutase) and concentration of malondialdehyde (MDA) in ischemic brain tissue in an experimental model of stroke.

Methods: Focal brain ischemia was established with the temporary occlusion of the middle cerebral artery for one hour in rats. Saffron (100 mg/kg) was given intra-peritoneally at the onset of ischemia. 24 hours later, brain edema and infarct volume were evaluated and glutathione peroxidase and superoxide dismutase activities and MDA concentration were measured in the ischemic brain tissue using a specific kit.

Results: The results showed that saffron reduced infarct volume by 77% (P<0.001) and brain edema by 60% (P<0.001) compared with the control group in 24 hours following ischemia. Moreover, saffron significantly reduced the content of MDA (P<0.001) and increased the activity of superoxide dismutase (P<0.001) and glutathione peroxidase (P<0.001) in the cortex of the ischemic brain tissue.

Conclusion: Saffron has protective effects against oxidative ischemic damage and brain edema in a transient model of focal cerebral ischemia in rats. This protective effect is probably induced by increasing the capacity of antioxidant enzymes and decreasing the production of free radicals.

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Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

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Background: Uterine environment and fetal period can profoundly affect health of the neonat. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates cellular stress responses and its activity is essential in both embryogenesis and postnatal life. The aim of the present study was to investigate the effects of maternal swimming on rat pups' HIF-1α levels as a key regulator of oxygen in lungs.

Methods: Sixteen female Wistar rats weighing 180- 200 grams were acclimated to a new environment consisting of equal light-darkness cycle and ad lib access to chow and adapted to the stress caused by water for two weeks. The rats were divided into two swimming and control groups. Swimming training began on the first day of pregnancy in a pool and continued for 3 weeks (1 h/day, 5 days/wk). Pups' lungs were removed two days after birth and their HIF-1α concentration was determined with enzyme-linked immunosorbent assay (ELISA). Statistical analysis of the data was done using independent t-test. A p-value smaller than 0.05 was considered statistically significant.

Results: Swimming lead to a significant (P<0.001) increase in the pups' lung HIF-1α levels compared with the control group. Although 3-wk period of swimming training, showed no significant increase in weight and also lung weight of newborns. Thus it can be concluded that swimming endurance training in pregnancy, can be considered as appropriate alternative in order to embryos development.

Conclusion: Our research suggests that HIF-1α level is an essential element for the development of the lungs of embryos. Moreover, further studies on the lung HIF-1α levels at post-natal period with different modes of exercise will provide more clear insight into the mechanisms of the findings resulting from this study.

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Background: Regarding the immunomodulatory effects of lactobacillus bacteria, this study aimed to evaluate the effect of oral administration of Lactobacillus reuteri, as probiotic bacteria, on natural killer cell cytotoxicity and tumor-specific lymphocyte proliferation in Balb/c mice with breast adenocarcinoma.

Methods: A total of 30 female mice, aged 6- 8 weeks and with a weight of approximately 17- 19 g, were randomly divided into two groups of 15 mice. The case group received Lactobacillus reuteri at a dose of 2.7× 108 bacteria in half a milliliter of sterile phosphate buffer saline (PBS) and the control group only received PBS. The probiotic group received the regimen for two weeks prior to tumor transplantation, as they did for 30 days after transplantation with three-day intervals and durations of seven days. For the evaluation of natural killer cell cytotoxicity and also tumor-specific lymphocyte proliferation response, LDH and BrdU assays were performed respectively according to the manufacturers' instructions.

Results: The study showed that the mice in the case group which were receiving Lactobacillus reuteri had statistically significant differences in the replication of tumor -specific lymphocytes, natural killer cell cytotoxicity and delayed hypersensitivity responses Compared to the mice in the control group.

Conclusion: Daily consumption of probiotics seems to regulate the immune system and consequently it can be helpful in people with cancer. Moreover, consumption of probiotics in healthy individuals can also boost the efficiency of the immune system against a variety of abnormalities.