Tehran University Medical Journal

---

Background: Aeromedical transport provides immediate advanced medical treatment for certain critically ill and injured patients, bringing about rapid treatment and decreasing the time of hospitalization. With the great expense of helicopter emergency medical services (HEMS), research and review of experience is conducted to determine areas in which the enforcement of standards will enable the effective and optimal use of HEMS.
Methods: We examined peer-reviewed published articles in French, English and Persian journals and medical texts to determine the best use of, and standards for, HEMS.
Results: We found that HEMS effectively improves health care in three categories of services: the rapid transportation of medical personnel/equipment to an accident and of patients to the hospital (primary response) meeting road ambulances at an intermediate point coming from a hospital or accident to transport patients to a hospital (secondary response) the planned urgent inter-hospital transfers of critically ill patients for specialized care (tertiary response). HEMS standards have been set for: the flight equipment and crew, the types of emergencies to which HEMS should respond, the optimal length of time for each part of the mission (call out time, response time, on-scene time, transport time, and total rescue time) and the affect on patient survival. Some other standards include: algorithms for patient screening, flight heights for different diseases and injuries, rooftop and parking garage helipad at hospital, approach of flight paths and the facility at the touchdown area. HEMS standard medical equipment includes those needed for telemedicine and basic and advanced life support. Standard drugs on board the HEMS vehicle depends on the type of the missions selected for HEMS. The area of medical crew members, as well as their fundamental and the continuing training, also has standards that must be met. The standard scoring system for severity of injury, and finally, the standard method for the annual calculation of the cost and benefit of using HEMS in a specified region have also been considered.
Conclusion: As trauma is a common reason for requesting HEMS in Iran, the decrease in "Golden Hour" response time for trauma patients is a priority. HEMS is expensive and enforcing standards also requires increased effort and expense. Nevertheless, both can reduce the morbidity, mortality and expense for longer hospital stays. Thus, the proper telemedicine and life support equipment and drugs, as well as algorithms for patient screening can improve HEMS efficacy. Furthermore, enforcing proper communication and record keeping regarding trauma severity for HEMS missions allows hospitals to predict the proper immediate treatment for incoming patients and its future need for HEMS services.

---

Background: Pi-GST and Mu-GST are subclasses of glutathione S-transferase that present on human sperm surface and play an important role against oxidative stress. Therefore, any defects in the enzyme activity may be associated with male infertility.In this study the polymorphisms of GSTM1 and GSTP1 in association with enzyme activity and sperm parameters were studied.

Methods: This case-control study involved 95 men with oligoastenoteratozoospermia and 26 controls with normozoospermia. Semen analyses were carried out according to WHO guidelines. Blood DNA was extracted using salting out procedures. GSTM1 and GSTP1 polymorphisms gene were determined through PCR-RFLP and multiplex PCR, respectively. Finally, Glutathione S-transferase activity was measured.

Results: Frequencies of GSTM1 null genotype in oligoastenoteratospermic and normospermic groups were 52.1% and 53.8% respectively. There were no statistically significant differences in sperm parameters and enzyme activity between GSTM1 null and positive genotypes in two groups. There were no statistically significant differences in glutathione S-transferase activity between oligoastenoteratospermia and normospermic groups (p>0.05). All the 121 men in this study had Ile/Ile genotypes at 105 codon of GSTP1. Frequency of normal homozygote (114Ala/Ala), heterozygote (114Ala/Val) and mutant homozygote (114Val/Val) genotypes in oligoastenoteratospermic group were 81.1%, 17.9% and 1.1% respectively but in the control group they were 88.5%, 11.5% and null.

Conclusions: Total glutathione S-transferase activity and sperm parameters were not affected by deficient Glutathione S-transferase activity in GSTM1 null genotype. Compensate activity of other sperm surface glutathione S-transferase isozymes, like GSTP1, may justify the cause.

---

Background: The transfer of multiple embryos during ART procedures (IVF/ICSI) in order to maximize the chance of pregnancy, has resulted in increasing rates of multiple pregnancies with a 20- fold increased risk of twins and 400- fold increased risk of higher order pregnancies with significantly high maternal and perinatal morbidity and mortality in comparison with singleton. Since at present there is no limitation in number of embryos being transferred in ART cycles in infertility centers in Iran, in order to evaluate the relationship between number of embryos transferred, pregnancy rates and multiple pregnancy, this study was performed in a referral university center.

Methods: In a cross sectional descriptive analytical study a total of 536 ART cycles in infertile patients treated at the Infertility Department of Vali-e-Asr Hospital & Vali-e-Asr Reproductive Health Research Center from October 1999- March 2003 were evaluated using a questionnaire dealing with the parameters affecting ART outcome.
Results: There was a total pregnancy rate of 21% with a multiple pregnancy rate of 12%. Increased age had a negative effect on pregnancy rate with a significant difference over 40 years (p<0.05). Pregnancy rate was higher with increased number of transferred embryos but it was only statistically significant when three versus two embryos were transferred (p<0.008). When more than three embryos transferred, although there was an increase in pregnancy rate, the difference was not statistically significant, but there was a significant increase in multiple pregnancy rate.
Conclusions: The maximum number of transferred embryos in ART cycles should not precede three embryos especially in age groups less than 40 and also when good quality embryos are available.

---

Background: Prohepcidin, a liver-derived peptide with antimicrobial properties, is regulated by factors such as iron load and inflammation. Hepcidin is a central player in iron homeostasis. It downregulates the iron exporter ferroportin, thereby inhibiting iron absorption, release and recycling. Thus, prohepcidin increases the possibility of iron-limited erythropoiesis and development of anemia. In end-stage renal disease (ESRD), plasma hepcidin levels are elevated, which may contribute to iron deficiency in these patients. This study was undertaken to investigate the relationship between prohepcidin and serum biochemical parameters related to anemia and inflammation in the aforesaid patients.

Methods: Fifty-four stable patients with uremia who were on chronic hemodialysis were enrolled in the study. The patients were withheld from intravenous iron two weeks prior to laboratory measurements. Later, (total) prohepcidin was measured by ELISA method as were other parameters including serum iron, TIBC, TSAT, Hct, ferritin, albumin, CRP, ESR, cholesterol and triglyceride.

Results: Serum prohepcidin levels were higher than normal values in the patients, but they were not correlated to the serum iron, TIBC, TSAT, Hct, ferritin, albumin, cholesterol and triglyceride (p>0.05). No significant association were also found with ESR (p=0.97, r= -0.005) or CRP (p=0.053, r =0.26).

Conclusion: Serum prohepcidin level was higher in chronic hemodialysis patients but it was not predictive of iron status or inflammatory conditions in these patients. Confirmation of these results may necessitate studies with larger sample sizes or measurement of the biologically active form of hepcidin.

---

Background: Hypercholesterolemia is considered a major risk factor for pancreatitis, atherosclerosis and coronary heart disease. Cholesteryl ester transfer protein gene polymorphisms are known to be associated with changes in lipid levels. We investigated the association between a polymorphism in the CETP gene (D442G) with plasma lipid levels and CETP activity in patients with hypercholesterolemia.

Methods: This case/control study that be done in Hamadan university of medical sciences (from October 2008 to September 2009), included 102 patients with hypercholesterolemia and 200 healthy individuals. Polymerase chain reaction and restriction fragment length polymorphisms were used to determine genotypic distribution and allelic frequencies of polymorphisms. The plasma CETP activity was measured by a kit in a fluorescence spectrometer. Lipid concentrations were measured by routine biochemical and enzymatic assays.

Results: Plasma cholesteryl ester transfer protein activity was significantly higher in the cases than the controls (P<0.05). The genotypic and allelic frequencies for this polymorphism were not statistically different between the patients with hypercholesterolemia and the controls (in controls: DD 96%, DG 4%, GG 0% and in cases: DD 86%, DG 10%, GG 4%), (P>0.05). Plasma HDL-C, LDL-C and TC were higher in both groups with GG and DG genotypes than with DD genotype, whereas serum CETP activity was lower in GG genotype compared with other genotypes (GD or DD), (P<0.05).

Conclusion: The results showed that D442G polymorphism of CETP gene was associated with changes in lipid profile and plasma CETP activity in the selected population and it might have a role in contributing to a genetic risk for developing coronary artery disease.

---

Background: Coronary heart disease (CHD) is a leading cause of death worldwide and hypertriglyceridemia and hypercholesterolemia are major risk factors for the disease. Considering the role of hyperlipidemia as the underlying cause of cardiovascular mortalities and morbidities, and the limited and conflicting results of studies on CETP gene polymorphisms in Iran, we aimed to study -971 G/A polymorphism of cholesterol ester transfer protein gene in patients with primary hyperlipidemia.
Methods: In this case-control study performed in Hamadan University of Medical Sciences (from May 2010 to April 2011), we recruited 200 patients with primary hyperlipidemia (total cholesterol >250 mg/dl and/or triglyceride >200 mg/dl) as the cases and 200 healthy individuals with normal cholesterol and triglyceride as the control group. Gene segments were replicated by polymerase chain reaction (PCR) and -971 G/A polymorphism genotypes were identified by RFLP technique. Subsequently, plasma CETP activity was measured enzymeatically by a kit in a fluorescence spectrometer.
Results: The allele and genotype frequencies were not significantly different (P>0.05) between the two groups (in the control group: AA 24%, GA 47% and GG 28.5% and in the case group: AA 18%, GA 51% and GG 31%). In the case group, homozygous individuals with A alleles (AA genotype) had greater cholesterol and HDL-c concentrations than those with other alleles (GG and GA). In both cases and controls, individuals with AA genotype had lower CETP concentrations.
Conclusion: We conclude that -971 G/A polymorphism in CETP gene promoter can affect lipid profile and alter CETP activity.

---

Background : One of the important problems in fertilization in vitro (IVF) is failure of implantation. This could be the result of estrogen and progesterone effects in endometrial acceptance during ovulation stimulation. Although progesterone has a vital role in primary phase of pregnancy, but the estradiol role in luteal phase is unknown. The aim of this study is assessment of the ratio of estradiol to progesterone in embryo transfer day on Intracytoplasmic sperm injection (ICSI) outcomes.

Methods : This is a cohort study. The subjects were 311 infertile women referred to Urmia Kosar infertility clinic & Urmia reproductive health research center who treated with ICSI method between August-Jan 2011 . Five cc blood was drawn for determine of estradiol and progesterone in transfer day. Transfer occurred after a variable in vitro culture period ranging from 48 to 72 hours after ovulation induction. Chemiluminescent ELICA the level of mention hormones was used to determine the ratio of the progesterone level to the estradiol serum level and was compared based on treatment outcomes.

Results : A total of 311 patients, 115 (37%) were pregnant and happened abortion were 18 (5.8%) . The mean ratio of estradiol to progesterone in transfer day in two groups of miscarriage/ non miscarriage and pregnant/ non pregnant was 32.26±23.86 , 28.17±26.5 and 28.58±2.4 , 36.09±4.39 respectively. There is no significant difference between two groups in regard of estradiol on progesterone ratio (P=0.5, P= 0.2) .

Conclusion: The results of this prospective cohort study show that there is no effect of estradiol to progesterone ratio on day of embryo transfer, successful pregnancy in ICSI cycles and abortion rate following of ICSI .

---

Background: Uterine myomas are benign tumors of the uterus and the most common solid pelvic tumors causing symptoms in approximately 25% of women in their reproductive years. However, its etiology and pathogenesis remain obscure there is increasing evidence that endometriosis is inherited as a complex genetic trait. Recent studies indicated the involvement of glutathione S-transferase M1 (GSTM1) gene in the pathogenesis of this disease and current investigations are devoted to the other members of phase II detoxification system genes such as glutathione S-transferase T1 (GSTT1). Therefore, current study was carried out to investigate the distribution of GSTM1 and GSTT1polymorphisms in Iranian population in order to estimate possible impact of null-alleles of each gene in development of this disease. Methods: In this study, 50 patients with endometriosis diagnosed by both pathology and laparoscopic findings according to the revised American Fertility Society classification of endometriosis were recruited from subjects referred to the Pasteur Institute of Iran between November 2012 to September 2013. Accordingly, controls (n=50) were subjects without any of aforementioned gynecologic conditions. The genomic DNA was extracted from peripheral blood leucocytes using the salting out method and GSTM1 and GSTT1 genotyping for gene deletions were carried out using Gap-polymerase chain re-action. Logistic regression analysis was applied to assess whether there was any significant risk increase between the case group with higher null genotypes compared to control group. The level of statistical significance was set at 0.05 and all analyses were conducted using the SPSS version 18.0 (SPSS Inc., Chicago, IL). Results: There was significant evidence that the distribution of the GSTM1 and GSTT1 genotypes differed between the patients and the controls with an allelic odds ratio (OR) of 3.56 (95%CI: 1.35-9.37, P=0.01) and 3.92 (95%CI: 1.4-10 P=0.009) respectively. Data analysis also revealed that individuals with both GSTM1 and GSTT1 null genotypes (-/-) had higher risk to develop the disease in comparison to the people with the both present (+/+) genotype (OR:19.23, P=0.007). Conclusion: The findings suggest that the GSTM1 and GSTT1 genetic polymorphisms are associated with the development of endometriosis in Iranian women which is in agreement with previous results obtained in other populations. However, the ethnic variations of polymorphisms should be evaluated in detail and differences should be incorporated into investigations of susceptibility variants for this disease.

---

Stem cells are undifferentiated and multi pluripotent cells which can differentiate into a variety of mature cells and tissues such as nervous tissue, muscle tissue, epithelial tissue, skeletal tissue and etc. Stem cells from all different source have three unique features: 1) Proliferative capability: Stem cells are capable of self dividing and self renewing for long periods or more than six months at least that called immortalization. 2) Undifferentiated nature: It’s considered as one of the essential characteristics of stem cell, so it doesn't have any tissue-specific construction. 3) Differentiation to the different cells from all organs: This ability can Induced by tissue specific transcription factors. Because of that, they are so important in prevention and treatment of human disease. Depending on the sources from which they derive, they have different types which can be used to produce special cells and tissues. The most significant types of stem cells are; embryonic stem cells (ESCs) which are derived from embryos, adult stem cells (ASCs) which are derived from differentiated cells in a specific tissue, induced pluripotent stem cells (iPSs) which are produced from adult differentiated cells that have been genetically reprogrammed to act resemble to an embryonic stem cell and cord blood stem cells which contains haematopoietic stem cells and derived from the umbilical cord after gestation. By providing a medium containing of special growth factor, it is possible to orientated stem cell differentiation pathway and gained certain cells from them. The important uses of stem cells includes damaged heart tissue cells improvements and bone tissue repairing, cancer treatment, damaged neurological and spinal tissue repairing, improving burns and injuries and the treatment of diabetes, infertility and spermatogenesis dysfunction. Furthermore, the application of them in gene therapy is an important issue in the modern medicine science due to the role of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

---

Results: The prepared lipopolyplex were 104 nm in size and all the lipopolyplexes were able to enhance transfection in the C/P=0.4 compared with its basic carriers (PEI and liposomes) alone, while showing less cytotoxicity than not manipulated liposomes. The results of this study suggest synthesized nanoparticles as nanocomposites for gene delivery purposes to different cells and in in-body studies. Conclusion: The results of this study show that the lipopolyplex constructed from combination of PEI and liposomes can efficiently transfer the gene to the cell, while showing low cytotoxicity and appropriate size at the nano-scale. Therefore, this lipopolymer can be suggested for gene delivery purposes to different cells and in vivo targets.