مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و چهارم شماره 1 (پیاپی 181، فروردین 1395)

Primary ovarian insufficiency (POI), commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%). The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH). There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and timing of fertility preservation by giving an estimated window of fertility. The objectives of the current review are to report on the etiology of POF induced through cancer therapy.

Infeliximab is a form of chimeric antibody which neutralizes the most important inflammatory cytokine, TNF-a, in inflammatory disorders. The aim of current study was to pilot expression of chimeric infliximab in Chinese Hamster ovary (CHO) cells.
In this research study, pVITRO2-neo-mcs vector that consist of infliximab light chain and heavy chain was used to transform into the E.coli by CaCl2 method. The plasmid was then purified and transfected to cultured CHO cells by Lipofectamine 2000® (Invitrogen GmbH, Germany). Transfected cells were selected upon G-418 treatment after 2 weeks and the level of expression, based on standard curve, was measured using IgG ELISA kit after 48 hours for each clone. High level expressed clone was then cultured in roller bottles and recombinant chimeric product was purified by protein A affinity chromatography. The purity of the product was analyzed by 10% gel SDS-PAGE from eluted samples. The efficacy of the purification was analyzed by ELISA before and after purification step. This article is a master's student thesis from February 2015 to August 2016 in pharmaceutical technology development center, Tehran University of Medical Sciences, Tehran, Iran.
The purified plasmid was analyzed on 2% agarose gel. After selective pressure of G-418, 10 stable transfect clones were assessed for infliximab secretion by IgG ELISA kit at 450 nm. The maximum and minimum expression which detected by ELISA were 23 ng/ml and 6 ng/ml, respectively. The band width of infliximab fraction during purification procedure was observed at 0.7-0.8 min. The efficiency of the purification by ELISA was 70%. On SDS-PAGE analysis, two bands, 25 and 50 kDa, respect to light and heavy chains of Infliximab, was confirmed the expression of recombinant protein.
In the current study, the construct for infliximab monoclonal antibody production was designed using genetic engineering techniques and the expression was confirmed by conventional molecular biology methods. The high yield production was carried out in semi-industrial scale using roller bottles with a 70 percentage of purification efficiency.

Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα) of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI). GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whereas GPVI is critically involved in platelets firm adhesion to the site of injury regardless of shear condition. During storage, platelets experience some changes that deleteriously affect the expression levels of platelet receptors, which in turn can alter platelet functional behaviors. Considering the important roles of GPIbα and GPVI in platelet adhesion, it seems that any dramatic changes in the expression levels of these receptors can influence adhesive function of transfused platelets. Thereby examining GPIbα and GPVI expression during the storage of platelet concentrates may provide some useful information about the functional quality of these products after transfusion.
In our experimental study, 5 PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO). All the platelet products met the standard quality assessment based on AABB (American Association of Blood Banks) guidelines. Washed platelets were subjected to flowcytometry analysis for the evaluation of GPIbα and GPVI receptor expression in day 1, 3 and 5 after storage. Data were presented as mean fluorescence intensity (MFI) and analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test.
The GPIbα expression on first day (MFI=86±5.9) was reduced three days after storage (MFI= 69±6.9). The expression levels continued to reduce until day 5 in which GPIbα expression was markedly decreased to (MFI= 61±7.7) (P= 0.0094). GPVI expression on the days 1, 3 and 5 after storage were 20.6±3.3, 24±2.5 and 14±4.9, respectively. The results showed a significant decrease of expression on day 5, compared to that in day 3 after storage (P= 0.0213).
Our study showed significant decreases in the expression of platelet receptors GPIbα and GPVI after 5 days storage, suggesting a major defect in adhesive function of platelets during this term.

Nano scale dendrimers are macromolecules synthetic which frequently used in medical and health field. Because traditional antibiotics inevitably induce bacterial resistance, which is responsible for many treatment failures, there is an urgent need to develop novel antibiotic drugs. This study was aimed to examine Synthesis and the antibacterial effect of NanoPolyamidoamine-G7 (NPAMAM-G7) dendrimer on Escherichia Coli, Proteus Mirabilis, Salmonella Typhi, Bacillus Subtilis and Staphylococcus Aureus.
In this experimental study that has been conducted in June 2015 in the Laboratory of Microbiology, Iran University of Medical Science, NPAMAM-G7 dendrimers was synthesized by Tomalia’s divergent growth approach. The antibacterial effects of NPAMAM-G7 dendrimer were studied by disc diffusion and micro-dilution method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against gram-positive and gram-negative bacteria were determined according to Clinical and Laboratory Standards Institute (CLSI) guideline. Standard discs were prepared using different concentrations of dendrimer on Mueller-Hinton agar plates.
Zone of inhibition in concentration 25 μg/ml of NPAMAM-G7 dendrimers for Escherichia Coli, Proteus Mirabilis, Salmonella Typhi, Bacillus Subtilis and Staphylococcus Aureus were 26, 38, 36, 22 and 25 mm, respectively. Regarding the zone of inhibition in gram negative bacteria with gram positive ones was P= 0.16 and was not significant difference. The MIC for Salmonella Typhi was 0.025, for Proteus Mirabilis, Bacillus Subtilis, Staphylococcus Aureus and Escherichia Coli was 0.25 μg/ml. The MBC for Salmonella Typhi was 25μg/ml, for Proteus Mirabilis and Bacillus Subtilis was 50 μg/ml and for Escherichia Coli and Staphylococcus Aureus was 100 μg/ml. The least of sensitivity against NPAMAM-G7 related to Escherichia Coli and Staphylococcus Aureus and the most of sensitivity related to Salmonella Typhi.
The NPAMAM-G7 dendrimer with end amine groups exhibited a positive impact on the removal of standard strains, gram-positive and gram-negative bacteria. Therefore, it is possible to use these nanodendrimers as antibacterial in the future.

It is reported that high frequency of chromosomal aberrations in peripheral blood lymphocytes of individuals is a marker of cancer predisposition. The aim of this study was to investigate the in vitro frequency of chromosomal damage in lymphocytes of patients with head and neck cancer against gamma irradiation compared with those in healthy individuals.
In a case and control study, peripheral blood lymphocytes of 101 patients with head and neck cancer were collected before the onset of radiotherapy. Lymphocytes of 40 healthy individuals were also collected as controls. Head and neck cancer patients and the control group were consecutively recruited between April 2012 and February 2015 from Clinics of Cancer Institute, Imam Khomeini Hospital, Tehran, Iran. Lymphocytes of patients or control group were cultured and exposed to gamma radiation in G2- and G0- phase of the cell cycle. The induced chromosomal aberrations such as chromosome and chromatid breakages, chromosome and chromatid gaps, chromatid exchanges and micronuclei were scored in one-hundred metaphase cells of each individual. The mean of each chromosomal aberration was compared in patient and control groups. Early and late tissue reactions were scored during radiotherapy treatment or thereafter.
There was no significant difference in demographic characterization between the two study groups. The frequency of radiation- induced G2 aberrations in lymphocytes of patients was significantly higher than in those of healthy donors (P= 0.001 for chromosomal breaks). The frequency of radiation-induced micronuclei in G0 assay was also higher in patients than in those in controls (P= 0.05). The results also indicate that there is no correlation between the two assays. No significant correlation was also observed between aberration frequencies in lymphocytes and the degree of both early and late normal tissue reactions.
The results indicate that the in vitro chromosomal radiosensitivity of peripheral blood lymphocytes of patients with head and neck cancer against gamma irradiation was significantly higher than that in healthy individuals.

High-resolution manometer (HRM) of the esophagus has become the main diagnostic test in the evaluation of esophageal motility disorders. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The first step of the Chicago classification described abnormal esophagogastric junction deglutitive relaxation. The latest classification system, proposed by Pandolfino et al, includes contraction patterns and peristalsis integrity based on integrated relaxation pressure 4 (IRP4). It can be discriminating the achalasia from non-achalasia esophageal motility disorders. The aim of this study was to assessment of clinical findings in non-achalasia esophageal motility disorders based on the most recent Chicago classification.
We conducted a prospective cross-sectional study of 963 patients that had been referred to manometry department of Gastrointestinal and Liver Research Center, Firozgar Hospital, Tehran, Iran, from April, 2012 to April, 2015. They had upper GI disorder (Dysphasia, non-cardiac chest pain, regurgitation, heartburn, vomiting and asthma) and weight loss. Data were collected from clinical examinations as well as patient questionnaires. Manometry, water-perfused, was done for all patients. Manometry criteria of the patients who had integrated relaxation pressure 4 (IRP4) ≤ 15 mmHg were studied.
Our finding showed that the non-achalasia esophageal motility disorders (58%) was more common than the achalasia (18.2%). Heartburn (68.5%), regurgitation (65.4%) and non-cardiac chest pain (60.6%) were the most common clinical symptoms. Although, vomiting (91.7%) and weight loss (63%) were the most common symptoms in referring patients but did not discriminate this disorders from each other’s. Borderline motor function (67.2%) was the most common, absent peristalsis (97%) and the hyper-contractile esophagus were rarest in the non- achalasia esophageal motility disorders.
However, achalasia is a treatable esophageal motility disorder but non-achalasia esophageal motility disorders were more common. Thus, manometrial study is an imperative tool for proper diagnosis and treatment of these patients, especially in gastro-esophageal reflux disease. Clinical finding could not accurately diagnosis between different types of non-achalasia esophageal motility disorders from each other’s.

Data mining is known as a process of discovering and analysing large amounts of data in order to find meaningful rules and trends. In healthcare, data mining offers numerous opportunities to study the unknown patterns in a data set. These patterns can be used to diagnosis, prognosis and treatment of patients by physicians. The main objective of this study was to predict the level of serum ferritin in women with anemia and to specify the basic predictive factors of iron deficiency anemia using data mining techniques.
In this research 690 patients and 22 variables have been studied in women population with anemia. These data include 11 laboratories and 11 clinical variables of patients related to the patients who have referred to the laboratory of Imam Hossein and Shohada-E- Haft Tir hospitals from April 2013 to April 2014. Decision tree technique has been used to build the model.
The accuracy of the decision tree with all the variables is 75%. Different combinations of variables were examined in order to determine the best model to predict. Regarding the optimum obtained model of the decision tree, the RBC, MCH, MCHC, gastrointestinal cancer and gastrointestinal ulcer were identified as the most important predictive factors. The results indicate if the values of MCV, MCHC and MCH variables are normal and the value of RBC variable is lower than normal limitation, it is diagnosed that the patient is likely 90% iron deficiency anemia.
Regarding the simplicity and the low cost of the complete blood count examination, the model of decision tree was taken into consideration to diagnose iron deficiency anemia in patients. Also the impact of new factors such as gastrointestinal hemorrhoids, gastrointestinal surgeries, different gastrointestinal diseases and gastrointestinal ulcers are considered in this paper while the previous studies have been limited only to assess laboratory variables. The rules of the decision tree model can improve the process of diagnosing and treatment of the patients with iron deficiency anemia and reduce their costs.

Many studies have reported the effect of metronidazole on reducing blood lipids in different ways, but there is no comprehensive estimation about its effect. Therefore, this study aimed to determine the effect of metronidazole on reducing blood lipid by meta-analysis method.
This is a systematic review based on the reliable local and international websites including SID, Magiran, Iranmedex, ISI, Pubmed and Scopus. The keywords used for searching were metronidazole, blood lipid, cholesterol, triglyceride, low density lipoprotein (LDL) and height density lipoprotein (HDL). All articles published until the end of March, 2015, about the effect of metronidazole on blood lipids reduction which met the inclusion criteria were reviewed. Three independent reviewers checked studies for quality and eligibility and finally extracted the data. The collected data were analyzed by meta-analysis method (random effects model) and by means of Stata, ver. 11.1 (College Station, TX, USA) with a significance level of less than 5%.
In 10 researches, 292 people had been studied and after taking metronidazole, the calculated amount of reduction in blood lipids was 11% (95% CI: 6%-16%) for cholesterol, 14% (95% CI: 4%-24%) for triglyceride and 8% (95% CI: 1%-15%) for low density lipoprotein (LDL) which was statistically significant (P= 0.001). The amount of increase in high density lipoprotein (HDL) was also calculated to be 1% (95% CI: 1%-2%) which was not statistically significant (P= 0.08).
The results of this study showed that, using metronidazole leads to decrease in the amount of cholesterol, triglyceride and low density lipoprotein (LDL) but it seems that it has not any effect on the increase in high density lipoprotein (HDL).

Laparoscopic cholecystectomy is a minimally invasive procedure whereby the gallbladder is removed using laparoscopic techniques. Monopolar electerosurgical energy is the method of dissection of gallbladder from liver bed. Ultrasonic energy causes less thermal damage and suggests an alternative to monopolar elevterocautery. Leptin is a tissue factor and C-reactive protein (CRP) is an acute phase protein that builds up in surgical damages. In laparoscopy, pneumoperitoneum and thermal damage cause this increase. In this study, after completion of surgery with both methods, plasma leptin and CPR were measured. Next, the complications and benefits of the two methods were compared.
This single blind randomized clinical trial was conducted on 78 patients who were candidate for laparoscopic cholecystectomy in surgery clinic of Razi Teaching Hospital in Ahvaz Jundishapur University of Medical Sciences from March 2013 to March 2015. Patients were divided randomly into two groups of ultrasonic and electerocautery. Then, leptin’s level and CRP’s level were measured at completion of surgery, 30 minutes after completion, 6 and 24 hours after completion of surgery in the two groups.
This study shows that the average rate of leptin at completion of surgery, 30 minutes after completion, 6 and 24 hours after completion of surgery in ultrasonic group had less increase than electerocautery group and the difference was statistically significant (P= 0.0001). The average rate of CRP at completion of surgery, 30 minutes after completion, 6 and 24 hours after completion of surgery in ultrasonic group had less increase than electerocautery group and the difference was statistically significant (P= 0.0001).
The level of leptin and CRP shows that surgery with ultrasonic method will provoke the immune system less than electerocautery method.

Herpes encephalitis is the most common cause of fatal encephalitis in the world which often presents with sudden fever, headache, seizure, focal neurologic symptoms, and consciousness loss. The aim of this study was to report a case of maternal death caused by herpes encephalitis which appropriate antibiotic therapy delayed because of early diagnosis of eclampsia.
A 16-year-old pregnant woman at 36th weeks of gestation was referred to gynecology emergency department of Ghaem Hospital, Mashhad University of Medical Sciences in 2016. She was admitted due to 4 times of generalized tonic-clonic seizures and blood pressure of 140/90 mmHg with diagnosis of eclampsia. Cesarean section was performed for fetal distress and eclampsia remote from delivery. 6 hours after cesarean section because of higher than 39 °C and reduction in consciousness status, she was transferred to intensive care unit (ICU). The first brain magnetic resonance imaging (MRI) was normal. Lumbar puncture (LP) was performed and brain MRI was repeated that increased signal was observed in two sides of basal ganglia. Intravenous acyclovir was administered by possible diagnosis of viral meningoencephalitis. Cerebrospinal fluid (CSF) was positive in terms of herpes simplex virus type 1 (HSV-1). Unfortunately, the patient died 35 days after hospitalization by diagnosis of HSV-1 encephalitis and bilateral infarction with frequent seizures and clinical manifestation of septic shock refractory to treatment.
Although the first diagnosis for generalized convulsion during pregnancy is eclampsia, but in case of recurrent and specially atypical seizures and low consciousness level, other diagnosis like meningoencephalitis, brain lesions and cavernous sinus thrombosis (CVT) must be considered and ruled out.