مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال هفتاد و دوم شماره 5 (پیاپی 161، امرداد 1393)

Asthma is a chronic inflammatory disorder of the airways, associated with airway re-modeling and hyperresponsiveness. It is expressed that asthma influences about 300 million people around the world, which is estimated to increase to about 400 million by 2025. The prevalence rate is 15 to 20 percent in children and 5 to 10 percent in adults, while its trend is still increasing. Inflammation plays an important role in the patho-physiology of asthma, which involves an interaction of different types of the immune cells and mediators. It leads to a number of pathophysiology changes, including bron-chial inflammation, airway obstruction, and clinical episodes such as cough, wheeze and shortness of breath. Asthma is now greatly being introduced as a heterogeneous disorder and it is pointed out to the role of T cells, including Th1, Th2, Th17, and regu-latory T cells. Other immune cells, especially neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also pro-duce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been recognized in clinical samples and mouse models of asthma. Different cytokines, including pro-inflammatory cytokines (such as TNFα, IL-1, and IL-6), T helper 2 cytokines (such as IL-4, IL-5, IL-9, IL-13), and growth factors (such as GM-CSF, PDGF) play a role in the pathogenesis of asthma. Indeed chemokines (such as MPC-1, RANTES, MIP-1) and the chemokine receptors (such as CCR3, CCR4, CCL11, CCL24, and CCL26) play an important role in the recruitment of circu-lating inflammatory cells into the airways in asthmatic patients and also is related with increased T helper 2 cytokines after inhaled allergens. Among new approaches, treat-ment of asthma with anti-cytokine drugs such as antibodies blocking IL-4, IL-5, IL-9 could reduce recruitment inflammatory cells into the airways and remodeling. The final perspective of asthma treatments would be to alter from the symptomatic treatments to disease modifying.

Bacterial vaginosis (BV) is the most prevalent causes of abnormal secre-tion in women at fertility age. Also, Bacterial vaginosis is one of the most common dis-eases in women who refer to gynecology clinic. The main cause of the pathogenesis is increasing pH of vagina due to reduced number of lactobacillus and growth of anaero-bic bacteria. Prevalence of BV varies between 10 to 30 percent in different societies. Amsel criteria is used as diagnostic test in BV. This interventional study was designed to assess the impact of vaginal lactobacillus suppository and metronidazole compared to metronidazole alone on the recovery and recurrence of bacterial vaginosis. This study was a prospective, randomized, double-blind clinical trial which was conducted on 130 women with bacterial vaginosis to compare the effects of vagi-nal lactobacillus suppository and metronidazole. Bacterial vaginosis was diagnosed us-ing Amsel criteria that based on some clinical symptoms. Patients were divided into two groups, first group were treated with oral metronidazole plus lactobacillus and second group were treated with metronidazole alone. Patients were followed-up one week and four weeks after initiation of the treatment. One hundred and thirty women completed the study. Patients were followed at one and four weeks after initiation of intervention. Amsel criteria and recovery rate in both groups compared before treatment one and four weeks after treatment. The crite-ria and treatment were significantly improved, but this improvement was higher and statistically significant in the metronidazole plus Lactobacillus group compared to sec-ond group (P< 0.0001). The protective effects of lactobacillus in dealing with anaerobic patho-gens as well as the negative impact of metronidazole on lactobacillus of vaginal flora, use of lactobacillus along with metronidazole especially in patients with recurrent infec-tions is recommended. In other words, using lactobacillus with metronidazole for treatment of bacterial vaginosis is more effective than metronidazole alone.

Rabies is an acute encephalitis that causes more than 60,000 deaths worldwide. The only way to save individuals bitten by a rabies-infected animal is the timely use of effective vaccines. Treatment with new generation vaccines is expensive. Therefore, there is a global movement towards the production of less expensive vaccines which retain and improve upon the quality and effectiveness of the vaccine. Production and evaluation of non-classical vaccines is one of the approaches taken in this regard. In this study, we describe a new eukaryotic expression system to express the nucleoprotein N gene of rabies virus which, if suitable, may be evaluated for anti-rabies vaccine production. The complete sequence of the N gene of rabies virus PV subtype was amplified by real-time polymerase chain reaction and cloned into the pCDNA3.1(+) vector. The cloned gene was excised from the vector by restriction enzyme digestion and sequenced. Due to mutations detected in the N gene, the gene coding sequence was purchased as a recombinant pGH/N vector. Vector pGH/N was amplified and following enzymatic digestion, the excised N gene was once again cloned into vector pCDNA3.1(+). Successful cloning was confirmed using restriction digests and quick check. The recombinant vector pCDNA3.1(+)/N was transformed into cultured BSR cells and protein N expression was analyzed using fluorescent antibody test (FAT). Electrophoresis confirmed amplification of the nucleoprotein N gene and subsequent restriction enzyme digestion showed that the N gene had been successfully cloned into the recombinant pCDNA3.1(+)/N vector. However, DNA sequencing revealed the presence of mutations within the N gene. Restriction digest of the commercial pGH/N vector showed that the N gene had been excised from the vector. Successful cloning of the N gene into the pCDNA3.1(+) expression vector was confirmed using restriction digests and quick check. Protein expression in BSR cells was assayed by immunostaining with anti-ribonucleocapsid FITC-conjugated antibody and visually confirmed by fluorescence microscopy. This study showed that the protein N of rabies virus subtype PV can be expressed in a eukaryotic expression system using the pCDNA3.1(+) expression vector.

Colorectal cancer is the third most common cancer in the world. Non-coding RNA especially miRNAs have important regulatory roles in cancer. miRNAs are small non coding RNA 21-23 nucleotides long which have different levels of expression between tumors and normal tissues. This study was designed to compare expression level of miRNA-21 between Iranian population colorectal cancer tissues and normal tissue. This case-control study has performed in medical genetics department of Tehran University of Medical Sciences from January to November 2013. We used 35 samples. The samples were isolated from tumor and adjacent normal tissues of colon. Thirty-five samples were divided into different groups according to cliniopathologic features including tumor size (>4 and <4 cm), metastasis (+ and -) and stage. After small RNA extraction from tissues by small RNA purification kit the quality and quan-tity of extracted RNA was determined using spectrophotometry. cDNAs were synthe-sized and real-time polymerase chain reaction carried out. Finally expression levels were statistically analyzed by LinRegPCR and REST software. miRNA-21 expression ratio in stages I, II and III were 1/804 and 4/574, re-spectively, the increase from stage III was statistically significant (P= 0.037). The ex-pression were also studied according to different clinicopathologic status of colon can-cer, tumor size (>4 and <4 cm) and metastatic (+ and -), miRNA-21 over expressed in both groups, however the increase was not statistically significant. In this study, we found miR-21 over-expression in advanced stage in tu-moral tissue comparing with normal adjacent tissue. This means perhaps in the future it would be possible to use miRNA-21 as an informative prognostic biomarker to guide for better treatment strategies for colorectal cancer patients. Our findings also indicate that miRNA-21 is a promising new molecular target for designing novel therapeutic strategies to control colorectal cancer.

Squamous cell carcinoma (SCC) is the most frequent oral cancer. Protec-tive effects of the consumption of vegetables and fruits on various forms of cancer in-cluding oral cancer have been determined. Tomato (Solanum lycopersicum L.) because of its lycopene and bioflavonoids contents possesses anti-carcinogenic properties. The aim of this study was to evaluate the preventive effects of tomato pulp on pre-neoplastic changes induced by 4-Nitroquinoline-1-oxid (4-NQO) in epithelial cells of lingual mucosa in the rats. Forty-eight male Wistar rats were randomly allocated into four equal groups. Group 1 served as control. Groups 2 to 4 assigned to receive 30 ppm 4-NQO in drinking water for 12 consecutive weeks. When the feeding of 4-NQO was started to the rats of groups 3 and 4, they received tomato pulp (20 and 40 ml/kg bw) daily through the oral gavage. Finally, histological evaluations for carcinogenesis were performed for tongues epithelial tissue. There were no pathological alterations in epithelial tissue of lingual mucosa in control rats. In the epithelial cells of lingual mucosa of 4-NQO treated rats, premalig-nant alterations appeared after 12 weeks of the last application of the drug. Administration of tomato pulp at both doses (20 and 40 ml/kg bw) during the experiment reduced the severity of the lesions, as well as caused a significant reduction in the frequency of pre-neoplastic lesions of tongue epithelial cells (P= 0.024 and P= 0.008). The incidence of severe epithelial cells dysplasia of lingual mucosa in the high dose treatment group was significantly smaller than of low dose treatment group (P= 0.037). The results obtained showed that tomato pulp is effective in inhibiting the development of neoplasms in epithelial cells of lingual mucosa induced by 4-NQO in the rat.

Early detection of fetal gender can provide an alarm for parents who complicated by genetic disorders. Moreover, the invasive tests are used for detecting any sex-specific genetic syndromes before 12 weeks of gestation. This study was de-signed to discover any association between placental location and fetal gender between 11 to 13+6 weeks of gestation. A cross-sectional study was conducted on 200 singleton pregnant women. They were referred for Down syndrome screening sonography to prenatal clinic, Imam Khomeini Hospital a tertiary referral university affiliated hospital, Ahvaz, Iran, in 2013. Women were included if they are singleton and at 11 to 13(+6) weeks gestational age. Exclusion criteria were multifetal, ectopic pregnancies, or dead fetus. Information about placental location (upper, middle, below, anterior, posterior), gravidity, and fetal gender were recorded. All participants of our study were evaluated by one trained gy-necologist in ultrasound examinations during nuchal translucency (NT) examinations. Ultrasonography was performed using the Accuvix V10 OB/GYN ultrasound. All patients were followed-up till delivery for confirming the predicted gender. Information regarding gender of newborn were collected using medical chart review or by phone contact. Among 200 placenta which had been assessed, 103 (51.5%) were anterior and 97 (48.5%) were posterior. Our results showed that 75 (72.8%) from girl cases had an anterior placenta, while just 28 (27.2%) from boy cases had an anterior placenta (P< 0.001). In addition, there was significant association between placental location regard-ing below, middle, and upper and fetal gender. According to our results, an anterior and posterior positions of the placen-ta had significant relation with fetal gender. Our findings are consistent with previous studies regarding prediction of fetal gender using placental location. We suggest that more research with large sample size is required as well as investigations with more de-tails about placental locations.

Identify the causes of complaints and contributing factors may reduce medical litigation. The aim of this study was to assess the cases of complaints in the field of psychiatric. This study was done in retrospective cross-sectional study method. We inves-tigated 27 cases of medical malpractice in the field of psychiatry that registered in higher disciplinary board of the Medical Council of Iran, from 2001 to 2010. We calcu-lated the absolute and relative frequency of variables after collecting all data and calculated the difference between malpractice and exculpation cases based on physicians profile by Pearson's chi-squared test and Fisher’s exact test. P< 0.05 was considered as statistically significant difference. The 24 people who died and their families protested against psychiatrist were enrolled in this study. Demographic information and other characteristics of the cases were collected. All participants had been men. Seventeen of 24 cases (70.84%) were in 30-50 year old group and seven of 24 cases (29.16%) were in > 50 year old group. The most common types of negligence were related to disregarding of governmental provi-sions (40%). The age, expertise and place of medical activities were variables that dif-ferent significantly between negligence and non-negligence groups (P< 0.05). The re-sults of the study showed eight cases of 24 cases (33%) in the lower board, nine cases of 24 cases (37.5%) in the appeals board and eight cases of 24 cases (33%) in the higher disciplinary board were acquitted. Based on the study findings, it appears that age, expertise and activity place are factors that can be effective in reducing malpractice in psychiatry.

Choriocarcinoma is a highly malignant form of gestational trophoblastic disease. It is characterized by metastatic potential, rapid growth and deeply invasion into blood vessel and then widespread dissemination metastasis. However, the most common sites of metastatic choriocarcinoma are lung, vagina, liver, and brain. But, metastatic choriocarcinomas rarely is extended to gastrointestinal system. It is im-portant to keep in mind that despite extensive metastasis, choriocarcinoma is very curable disease. Due to high responsibility of this disease, early diagnosis of choriocarcinoma and treatment with chemotherapy can prevent mortality and morbidity of these patients. In this case report, we present a rare case of metastatic choriocarcinoma in the small bowel after normal term pregnancy. A 34-years-old woman G4, P4, L4 presented with abnormal postpar-tum vaginal bleeding (45 days) and unresponsive to usual medical and surgical therapy (oxytocine, metergene, antibiotic, and double curettage). The patient was admitted in the Ghaem Hospital, Mashhad University of Medical Sciences in April 2013. She suf-fered from rectal hemorrhage and severe weakness. Because of unsuitable condition (shock), laparotomy was performed and small bowel involvement was observed. Seg-mental resection of small bowel detected metastatic choriocarcinoma of the lesion. We couldn’t rescue our patient due to unresponsive to combination chemotherapy (actino-mycine, methotrexate, cyclophosfamide, vincrystine, etopuside). In abnormal postpartum hemorrhage, we should consider the possibility of choriocarcinoma. Although, it is important to note rare manifestations of metastatic choriocarcinoma of small bowel in massive gastrointestinal hemorrhage.