Iranian Journal of Basic Medical Sciences
Year:2013 | Volume:16 | Issue:5|Papers Count:11

Sir, the recent publication on “Publication Ethics” is very interesting (1). The article by Fazly Bazzaz and Sadeghi demonstrated many interesting cases of misconducts. Indeed, the misconducts can be seen in many ways. As mentioned in the present publication, both author and editor can perform publication misconducts. Nevertheless, the problem has many more facets. Sometimes, the misconducts are generated by the third parties. For example, the publisher can perform publication misconduct.

Objective(s): Previous studies have shown that thyroid hormones are necessary for normal development of many organs and because of the importance of skin as the largest and the most important organ in human body protection in spite of external environment, the study of thyroid hormones effects on skin development is considerable. In this survey we have tried to study the effects of maternal hypothyroidism on skin development in fetus during pregnancy and lactation by immunohistochemistry technique.Materials and Methods: Rats were divided into 4 groups, hypothyroids, hyperthyroids, hypothyroids are treated with levothyroxin and a control group. The rat mothers were exposed to PTU with 50 mg/lit dosage and levothyroxin with 1 mg/lit dosage and PTU and levothyroxin simultaneously and with the same dosage respectively in hypothyroid, hyperthyroid and treated hypothyroids with levothyroxine groups. After 14 days, blood sample was taken from mothers, and if thyroid hormones level had change well, mating was allowed. After pregnancy and delivery, 1th day dorsal skin (as the sample for pregnancy assay) and 10th day skin (as for lactation assay) was used for immunohystochemical and morphometric studies.Results: In this study it was observed that maternal hypothyroidism during pregnancy and lactation causes significant increase in laminin expression, in most areas of skin, and maternal hyperthyroidism during pregnancy and lactation causes significant decrease in laminin expression. Also significant decrease was observed in hair follicles number and epidermis thickness in hypothyroidism groups.Conclusion: This study showed maternal hypothyroidism causes significant decrease in epidermis thickness and hair follicles number and it causes less hair in fetus. Also maternal hypothyroidism causes large changes in laminin expression in different parts of skin. At the same time,maternal hyperthyroidism causes opposite results. In fact, thyroid hormones regulate laminin expression negatively which means increase in thyroid hormone level, decreases laminin expression. So changes in thyroid hormones level can influence skin development significantly.

Objective(s): Hypoxia is a serious challenge for treatment of solid tumors. This condition has been manifested to exert significant therapeutic effects on glioblastoma multiform or (WHO) astrocytoma grade IV. Hypoxia contributes numerous changes in cellular mechanisms such as angiogenesis, metastasis and apoptosis evasion. Furthermore, in molecular level, hypoxia can cause induction of DNA breaks in tumor cells. Identification of mechanisms responsible for these effects can lead to designing more efficient therapeutic strategies against tumor progression which results in improvement of patient prognosis.Materials and Methods: In order to identify more hypoxia regulated genes which may have a role in glioblastoma progression, cDNA-AFLP was optimized as a Differential display method which is able to identify and isolate transcripts with no prior sequence knowledge.Results: Using this method, the current study identified 120 Transcription Derived Fragments (TDFs) which were completely differentially regulated in response to hypoxia. By sequence homology searching, the current study could detect 22 completely differentially regulated known genes and two unknown sequence matching with two chromosome contig and four sequence matches with some Expressed Sequence Tags (ESTs).Conclusion: Further characterizing of these genes may help to achieve better understanding of hypoxia mediated phenotype change in tumor cells.

Objective(s): Osteoarthritis (OA) or degenerative joint disease is the commonest form of arthritis and can lead to joint pain, decrease in joint’s range of motion, loss of function, and ultimately disability. Exercise is considered as one of the non-pharmacological treatments of OA. But the effects of exercise on knee joint cartilage remain ambiguous. The aim of the present study was to investigate the effect of a four-week moderate treadmill exercise on rats’ knee osteoarthritis.Materials and Methods: Eighteen male Wistar rats (173±1 g, 8 weeks old) were randomly divided into three groups (n = 6): Intact control, monosodium iodoacetate (MIA) only (OA), and training. The osteoarthritis model was induced by intra-articular injection of monosodium iodoacetate (MIA). Subjects followed a moderate-intensity exercise program for 28 days. Rats were killed after 28 days and histological assessment was done on their knee joints. One-way ANOVA (P<0.05) and post-hoc Tukey test was used for the statistical analysis.Results: Histological assessment on 3 measurements of, depth ratio of lesions (P=0.001), total cartilage degeneration width (P=0.001), and significant cartilage degeneration width (P=0.001), demonstrated that moderate exercise for 4 weeks could surprisingly almost treat OA symptoms of rats’ knee joints.Conclusion: The findings of the present study indicate that a moderate treadmill exercise program exert a beneficial influence on rats’ knee osteoarthritis.

Objective(s): Pre-eclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Endothelial dysfunction is thought to be a central pathogenic feature in preeclampsia on the basis of elevated adhesion molecules. The aim of this study was to determine the level of plasma serum level of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1(ICAM-1), high sensitive C- reactive protein (hs-CRP) in pre-eclampsia and to compare hs-CRP levels between normal pregnant women, mild and severe pre-eclampsia.Materials and Methods: A cross-sectional study was conducted to determine the plasma concentrations of sVCAM-1, ICAM-1 and hs-CRP in peripheral blood obtained from normal pregnant women (n=40), mild pre-eclampsia (n=37) and severe pre-eclampsia (n=38). Concentrations of soluble adhesion molecule was determined with enzyme linked immunosorbent assay (ELISA).Results: There were significant difference in the means serum hs-CRP between normal pregnant women and mild pre-eclamptic women (P<0.05). Serum concentration of hs-CRP, sVCAM-1(ng.ml) and sICAM-1(ng.ml) were significantly higher in severe pre-eclampsia (P<0.05) than normal pregnancy. There were also significant differences in hs-CRP, s ICAM- 1 and in sVCAM- 1 levels between mild and severe pre-eclampsia (P<0.05). There was no difference in the mean plasma log sVCAM-1, sICAM-1 between normal pregnant women and mild pre-eclamptic women.Conclusion: We have determined the serum concentration of soluble adhesion molecule ICAM-1, VCAM-1 and hsCRP in normal pregnancy and pre-eclampsia. Adhesion molecule is elevated in severe pre-eclampsia compared with normal pregnancy, hsCRP are elevated in severe preeclampsia compared with mild preeclampsia and normal pregnancy and may be useful in predicting the severity of pre-eclampsia.

Objective(s): As far as we know, there has been no report regarding the effects of opium addiction or dependency of both parents on the learning and memory process in offspring. The aim of this study was to examine the learning and memory changes of adult male offspring whose mothers, fathers and/or both parents had dependency to opium before and during pregnancy.Materials and Methods: All experiments were carried out on Wistar rats. Opium dependency was induced by daily injections of opium (10 mg/kg/SC, bid/10 d) before mating. The presence of a vaginal plug was designated as gestation day. Treatment with opium continued through breeding and gestation until parturition. Spatial memory was tested in male offspring of control, saline and prenatal opium treated groups by a training trial and the probe test in the Morris water maze. Swimming escape latency in the maze and the ability to find the platform in the training trial were recorded. The time spent in the trigger zone and number of times the rats crossed the platform during the probe phase and swimming speed were measured.Results: The data revealed increased escape latency and a greater distance traveled to find the hidden platform in the offspring’s whose mother, father and /or both parents were exposed to opium. Crossings to target quadrant at probe trials was significantly reduced in all of the prenatal opium exposed off springs. The swimming speed showed a significant increase in father and parent’s opium exposed offspring.Conclusion: Prenatal opium exposure of either parent may cause deficits in spatial learning, but the precise mechanisms (s) remain largely unknown.

Objective(s: Cleft lip/palate are common congenital anomalies, affecting approximately 2/1000 live births. Pierre Robin Sequence is a subgroup of the cleft palate population. Chromosomal abnormalities near the SOX9 gene disrupt the regulation of this gene and prevent the SOX9 protein from properly controlling the development of facial structures, which leads to isolated PRS. The present study was conducted to identify the role of the SOX9 gene in the etiology of Pierre robin syndrome and to study the association of SOX9 and PRS in regulating morphogenesis of the face in individuals with Cleft lip/Palate using the PCR technique and GTG banding.Materials and Methods: Molecular and cytogenetic analysis was performed in 27 subjects with cleft lip/palate and 13 age matched controls. DNA was isolated and PCR was performed for the amplification of the gene of interest and the products were run on a 2% Agarose gel and the band patterns were analyzed. The chromosomal abnormalities were analyzed from the cultured lymphocytes after GTG banding.Result: Out of 27 patients screened, deletion of the SOX9 gene was observed in 1 case for exon1 and in 2 cases for exon2. The cytogenetic analysis showed no structural or numerical abnormalities and all the patients showed normal karyotype.Conclusion: The results of molecular methods showed a positive association suggesting that the SOX9 gene is of particular importance, but the cytogenetic study didn’t seem to show a stronger association suggesting that, this method would not identify disease genes acting via other mechanisms of genetic dominance and also due to the fact that Cleft lip / palate has a multifactorial inheritance.

Objective(s): In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation.Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4×1013 n.cm-2.s-1. The product was converted into chloride form which was further used for labeling of177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 mCi/100 ml) was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days.Results: The complex was successfully prepared with high radiochemical purity (>99.9%). Approximately, the whole injected dose has remained in injection site seven days after injection.Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.

Objective(s): Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC) exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms.Materials and Methods: NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase- 9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively.Results: Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax.Conclusion: Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.

Objective(s): In this study, 166Ho-1, 2-propylene di-amino tetra (methy1enephosphonicAcid) (166Ho-PDTMP) complex was prepared as a bone palliation agent.Materials and Methods: The complex was successfully prepared using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1×1013 n.cm-2.s-1) of natural Ho(NO3)3 samples followed by radiolabeling and stability studies. Biodistribution in wild type rats was also peformed.Results: The complex was prepared with the specific activity of 278 GBq/mg and high radiochemical purity (>99%, checked by ITLC). 166Ho-PDTMP complex was stabilized in the final preparation and in the presence of human serum (>90%) up to 72 hr. The biodistribution of 166Ho-PDTMP in wild-type rats demonstrated significant bone uptake was up to 48 hr compared to 166HoCl3.Conclusion: The produced 166Ho-PDTMP properties suggest a possible new bone palliative therapeutic to overcome the metastatic bone pains.

Objective(s): Noise-induced hearing loss (NIHL) is the major cause of acquired hearing loss. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, is a non- steroidal anti- inflammatory drug (NSAID) with known antioxidant and antineoplastic activity. Therefore, we monitored the extent of temporary noise- induced threshold shifts (TTS) and cochlear damage caused by high level 4- kHz noise exposure to verify the differences with those pretreated with celecoxib.Materials and Methods: Ten male albino guinea pigs (300-350 g in weight) were randomly allocated into two groups: the primal group was exposed to 4- kHz octave band noise at 102 Db SPL for 3 hrs (group 1, n=5); the latter pretreated with 50 mg/ kg celecoxib for 3 days, then exposed to noise (group 2, n=5). Before exposure and one hr after noise exposure, threshold shifts were evaluated with auditory brainstem responses (ABR) and finally the animals were euthanized for histological evaluation.Results: Comparing the threshold shifts before/after noise exposure with those pretreated, we found out that TTS caused by noise exposure did not show significant mitigation by celecoxib. By observing the organ of Corti at lower middle turn of cochlea in celecoxib pretreated group, considerable hair cell loss was discovered.Conclusion: The current study clearly confirmed that celecoxib had no attenuation against temporary noise-induced hearing loss.